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Biomedical subjects

G Kolb

Publications and source records attributed to G Kolb.

50 records · Page 3Linked to original sources

Granulocyte-related bioincompatibility of hemodialysis: inhibition of oxidative metabolism, degranulation reaction, enzyme release and leukocyte sequestration in the lung.

Hemodialysis (HD) induced contact of granulocytes with cuprophan and modified cuprophan, i.e. hemophan, membranes leads to over-stimulation of their oxidative metabolism. This is shown by the fact that after starting HD the peripheral granulocytes are less stimulable to chemiluminescence (CL) and peroxide production (cytochrome C reduction). Such alterations are likely to be connected with a granular staining loss, enzyme release and sequestration of granulocytes in the lung, which coincides with reported clinical features like dyspnoea and drop in arterial oxygen pressure. HD with polysulfone membranes causes a degranulation reaction too, but does not produce granulocyte inhibition and pulmonary sequestration of leukocytes, clearly indicating that these phenomena strongly depend on the different dialyzer membranes.

Biocompatible Materials↗

Detection of granulocyte elastase specific IgG split products in rheumatoid synovial fluid.

In vitro granulocyte elastase is known to cleave a large number of substrates e.g. complement components, fibrinogen, collagen and IgG. In vivo the enzyme is rapidly complexed by the plasma inhibitors a1proteinase inhibitor (a1PI) and a2macroglobulin. Therefore in biological fluids elastase is measured as the inactive a1PI-complex. We present a radioimmunoassay for elastase specific IgG split products as marker for the elastase activity in vivo. Elastase splits human IgG1 in Fab and Fc fragments and low molecular weight peptides. We produced specific antibodies against the elastase induced Fc fragment by immunization with an elastase generated peptide. After purification of the antibodies there is no crossreactivity with native IgG nor with similar Fc fragments produced by plasmin or papain. The elastase specific IgG split products are detected in synovial fluid samples of patients with rheumatoid arthritis. The measured concentrations are higher in the RA group than in control groups of patients with other inflammatory joint diseases.

Arthritis, Rheumatoid↗

Neoantigenic group on Fc fragments in rheumatoid arthritis synovial fluids.

Expression of neoantigens during denaturation of IgG by oxygen radicals or proteolysis was assumed to be a possible mechanism for stimulation of rheumatoid factor (RF) formation and/or granulocyte dependent inflammative joint destruction. The so-called human leukocyte elastase (HLE) regularly released by stimulated neutrophils f.e. into the RA synovial fluid is known to split IgG in vitro into papain like fragments and low molecular weight peptides. The n-terminal site of the HLE related Fc is bearing a neoantigenic group which is located near the hinge region but not expressed by the native IgG. The neoantigen itself is represented by the low molecular weight peptides produced by prolonged HLE-IgG proteolysis. Detection of HLE generated Fc in synovial fluids was performed by radioimmunoassay specific for the neoantigen. Patients were divided into the three groups; I RA (n = 23), II inflammative joint effusions except RA (n = 23), III osteoarthritis and trauma (n = 19). The biological effect of the neoantigen on to granulocyte oxidative metabolism was tested by Cytochrome C reduction and chemiluminescence. Neoantigen bearing Fc could be detected in 15 of 23 cases of group I, in group II in 11 of 23 cases and only in 7 of 19 cases in group III. The median concentrations were 0.62 micrograms in group I and zero in II and III. The HLE derived Fc were able to inhibit the oxidative metabolism of activated granulocytes in vitro. The O2- production of stimulated granulocytes was depressed dose dependent by the neoantigen. The neoantigenic group itself does not react with RF as proved by nephelometric titration of HLE derived Fc, neoantigenic peptide and native IgG against a RF standard.

Antigens↗

Neutrophil function in patients with localized juvenile periodontitis and with rapidly progressive periodontitis.

PMN chemotactic function and oxydative metabolism were investigated in 13 patients with rapidly progressive periodontitis (RPP) and 9 patients with localized juvenile periodontitis (LJP) using a chemotaxis assay (CHA), luminol chemiluminescence (CL) and nitroblue-tetrazolium (NBT) tests. In the LJP patients there was a significantly lower CHA than in the RPP patients (less than 40%). Three out of the 13 RPP patients displayed a cell-dependent increase of CHA and in 3, the reduced CHA measured was serum-associated whilst among the 9 LJP patients, a cell-dependent defect of CHA was present in 5 patients, a serum-associated defect in one patient and a combined cell- and serum-associated defect was found in another patient. The average values of CL in the RPP patients were significantly lower (1309.3 +/- 814.2) than those measured in the LJP group (2208 +/- 826.9). In contrast, the mean NBT test values indicated a lower phagocytic function in the LJP patients than in the RPP ones suggesting also the presence of a serum-dependent factor in RPP and that of a combined cell- and serum-response in LJP. According to these results, the neutrophil dysfunction in RPP, as indicated by both the chemotaxis and the oxydative metabolism nature, was frequently associated with a serum factor.

Adolescent↗

[A new method for rapid and simple adsorption of rheumatoid factors from serum].

It is well known that autoantibodies directed against human gamma-globulin, the so called rheumatoid factor (Rheumafaktor), show interference with immunochemical methods. Especially the enzyme-linked immunoassays for detecting the early immune reaction against virus-infections (e.g. rubella, measles, and others) show irregular positive results, if the tests are performed in samples containing IgM rheumatoid factor. We describe a new method for the rapid adsorption and elimination of rheumatoid factor from rheumatoid factor containing serum samples, using a suspension of glutaraldehyde-cross-linked, aggregated IgG in a combined solid- and liquid-phase technique. The bound rheumatoid factor can be subsequently desadsorbed at acid pH so that after washing in neutral-buffer or physiological saline the adsorption-material can be used again. Specific antibodies were not adsorbed.

Adsorption↗

Cleavage of IgG by elastase-like protease (ELP) of human polymorphonuclear leukocytes (PMN): isolation and characterization of Fab and Fc fragments and low-molecular-weight peptides. Stimulation of granulocyte function by ELP-derived Fab and Fc fragments.

The elastase-like protease (ELP) from human polymorphonuclear granulocytes (PNM) is able to split human IgG into Fab and Fc-like fragments and smaller peptides. These fragments are similar but not identical to those produced by papain. They differ in their electrophoretical mobility as well as in their molecular weights. Both ELP-Fab and papain-Fab show antigen-binding capacity. In contrast to papain-derived split products of IgG, the ELP-generated Fab and Fc fragments could enhance granulocyte function. Both ELP-Fab and ELP-Fc increase the spontaneous reduction of nitroblue-tetrazolium (NBT) in granulocytes dose-dependent in a homologous as well as in an autologous system. Furthermore, the ELP-derived Fab and Fc induce an active release of ELP by PMN. It could also be demonstrated that Fab as well as Fc increased the peroxidase activity in granulocytes.

Humans↗

Diagnostic value of CA 19-9 in patients with pancreatic cancer and nonspecific gastrointestinal symptoms.

Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n = 347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n = 126) than in those with unresectable tumors (n = 221, P < 0.0001; sensitivity 74% vs. 90%). CA 19-9 levels dropped sharply after resection but normalized in only 29%, 13%, and 10% of patients with stage I, II, and III tumors, respectively. In unresectable tumors no significant decrease in CA 19-9 levels after laparotomy or bypass surgery was found. Among patients with the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those who had postoperative CA 19-9 levels that decreased but did not return to normal (stage I, 33 months vs. 11.3 months; stage II, 41 months vs. 8.6 months; and stage III, 28 months vs. 10.8 months). In patients with recurrent disease, 88% had an obvious increase in CA 19-9 levels. CA 19-9 measurement is a simple test that can be used for diagnosis, for evaluation of resectability, and for prediction of survival after surgery and recurrences.

Adenocarcinoma↗

[Paradoxic occurrence of symptoms of rheumatic fever after thrombolytic therapy with streptokinase--a case of delayed hypersensitivity?].

We report the case of a 51-year-old patient with a Paget von Schrötter-Syndrome of the right arm who underwent a successful lysis therapy with 9 x 10(6) IU streptokinase (Streptase) i.v. over 3 days. 36 h after ending the lysis therapy he developed a generalized eczema, which was interpreted as a drug-induced allergic reaction of the arthus type (Coombs III). He received methylprednisolone p.o. with an initial dose of 40 mg, tapered to 0 over 5 days. One day after the efflorent rash the patient developed fever for 12 h (with 38.8 degrees C maximum) and a gonarthritis of the left knee, and 24 h later of both knees. An echocardiogram showed a small pericardial effusion without hemodynamic influence. On the following 2 days a minimal proteinuria of 0.28 and 0.22 g/l was found. Subsequently and after a follow-up of 2 years, the patient was totally free of pathologic clinical and laboratory findings. We interpret this unusual case as a delayed hypersensitivity reaction to streptokinase with a paradoxical occurrence of clinical symptoms formally fulfilling the diagnostic criteria of "rheumatic fever".

Arthritis, Reactive↗

Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy.

Superoxide production by neutrophils is believed to contribute to the efficiency of the host defence system. This activity is stimulated by the mannose-specific lectin concanavalin A, the N-acetylglucosamine/neuraminic acid-specific wheat germ agglutinin and the galactoside-specific lectins from Viscum album and human placenta. To assess whether this aspect of immune function is affected in cancer patients without or with treatment, neutrophil preparations from 69 patients were examined. Reductions in O2.(-)-production were observed for bronchial carcinoma patients after incubation with concanavalin A and the human lectin, while samples from breast cancer patients without or with treatment exhibited no significantly altered activity in the presence of each of the four agglutinins. Chemotherapy of lung and colorectal carcinoma patients reduced the neutrophilic response to concanavalin A and Viscum album agglutinin. As similarly shown for 9 specimens from other carcinoma types and from hemopoietic malignancies, there is no general impairment of responsiveness. In addition to the property of the lectin, the large extent of interindividual variation should be taken into account when it is attempted to enhance this factor of the host defence system against infections and malignant cells.

ABO Blood-Group System↗