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Biomedical subjects

U Rother

Publications and source records attributed to U Rother.

At least 37 records · Page 2Linked to original sources
PubMed1987

Persistently circulating C3 nephritic factor (C3 NeF)-stabilized alternative pathway C3 convertase (C3 CoF) in serum of an 11-year-old girl with meningococcal septicemia--simultaneous occurrence with free C3 NeF.

Hemolytic complement was found to be absent in the serum of an 11-yr-old girl (R.N.) with meningococcal septicemia. C1, C4, and C2 were slightly decreased, C3 was absent, C5-C9 within the normal range. B levels immunochemically and electrophoretic mobility of B were normal. C3d was greater than 1000% of a pooled EDTA-plasma standard indicating hypercatabolism of C3. On incubation of the patient's serum with normal human serum activation of C3 occurred even in the presence of 0.04 M EDTA. The amount of C3b generated was, however, greater without any chelating agent or in Mg-EGTA. On gel filtration of the serum two protein containing peaks were found to be responsible for activation of C3: the IgG containing peak was able to activate C3 in normal human serum without chelating agents and in Mg-EGTA but not in the presence of EDTA. The IgM-containing peak activated the third component of complement even in the presence of EDTA. The factor responsible for this phenomenon was termed C3 converting factor (C3 CoF). The IgG fraction of the patients serum caused activation of C3 in Mg-EGTA. However, in the presence of EDTA no activation of C3 could be induced even if physiological concentrations of the patients IgG were added to normal human EDTA-plasma. Thus the activity of the patient's IgG did not differ from typical C3 nephritic factor. The decay of C2 in EAC42 intermediates in the presence of the patient's IgG was uninfluenced indicating that it did not carry autoantibody activity against the classical pathway convertase C4b,2a, an activity recently termed NFc.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1987

Genetic polymorphism of C3 and Bf in IgA nephropathy.

C3 and Bf alleles were examined in the general population, in 67 patients with biopsy-confirmed mesangial IgA nephropathy and 81 patients with other types of glomerulonephritis, from the Heidelberg and Leiden renal programmes respectively. In both populations, a significant excess of homozygous phenotype C3FF (3.4% in controls; 10.4% in IgA nephropathy) and a deficit of C3FS heterozygous phenotype (35.8% in controls; 19.4% in IgA nephropathy) were observed in patients with IgA nephropathy, but not in other types of glomerulonephritis. No difference of C3 gene frequencies was found. C3FF was associated with an adverse clinical outcome (a higher prevalence of renal failure and hypertension). A significant excess of Bf-F gene frequency was noted (0.20 in controls; 0.33 in IgA nephropathy). In addition, an excess of phenotype BfFF was found (none in controls; 10.4% in IgA nephropathy). BfFF homozygotes also carried a higher risk of an adverse outcome (renal failure and hypertension). The data suggest a role for genetically coded (presumably) immunological factors in the genesis and course of IgA nephropathy.

Adult↗
PubMed1987

[Complement activation following head and brain trauma].

The prognosis for a patient with a severe head injury is dependent not only upon the location and the degree of this trauma, but also upon additional complications. For example, disseminated intravascular coagulation (DIC) can occur because of the thromboplastic activity of the damaged brain tissue that enters the circulation. The complement (C) system is activated by certain enzymes that cleave the clotting factors. Therefore, after head injuries we searched for C activation because it could result in the adult respiratory distress syndrome (ARDS). Patients and methods. We had two groups of patients: (1) 23 with large destruction and (2) 13 with little destruction of the brain tissue. Eighteen patients in group 1 and 8 in group 2 had isolated brain trauma. Blood samples were taken--upon arrival at the hospital and then 1, 3, 7, 12, 24, and 48 h later; after that we took weekly blood samples up to the completion of their treatment in the intensive care unit. We measured the total hemolytic serum C activity (CH50), activation of alternative pathway hemolysis (APH50), cleavage products C3a and C3d, and total protein. Furthermore, we studied the coagulation parameters of the extrinsic (prothrombin time) and intrinsic (partial thromboplastin time) pathways and fibrinogen content. From the patients records we extracted clinical parameters such as neurological status, intracranial pressure, pathological details on computer tomography hemoglobin and arterial-alveolar oxygen difference. Results. Figure 1 shows the different reactions of the C system in both groups: while patients of group 1 suffered from a decrease in total and alternative hemolytic activity, the other group increases in both parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Functional analysis and quantification of the complement C3 derived anaphylatoxin C3a with a monoclonal antibody.

The C3 fragment C3a belongs to the anaphylatoxins. It has immune regulatory activity and contributes to the pathogenesis of the adult respiratory distress syndrome (ARDS). The low molecular weight (9 kD) of C3a complicates the production of antibodies to C3a. We obtained a monoclonal antibody (designated H13) to human C3a. It reacts with C3a or C3a-desArg and with native C3 but not with C5 or C5a. In immunoblot analysis it reacts with the alpha- but not with beta-chain of C3 and binds to a protein with a mol. wt of about 10 kD present in zymosan-activated sera which is only marginally detectable in nonactivated serum and absent in plasma. H13 crossreacts with the analogous proteins of rabbit, guinea pig and sheep. H13 has the capacity to bind 125I-radiolabelled C3a efficiently but fails totally to react with 125I-C5a or with other C3 alpha-chain fragments. H13 blocks C3a functional activity. It markedly inhibits C3a-induced 3H-serotonin release from platelets in vitro and similarly inhibits the C3a-induced extravasation of Evans blue into the skin in vivo. H13 does not interfere with the haemolytic activity of C3. An ELISA system was established using H13 which permits quantification of C3a in sera of polytrauma patients. The antibody H13 should facilitate further functional analysis of C3a in experimental systems. It should be useful for quantification of C3a in diagnostic assays and also for application in immunopathology.

Animals↗
PubMed1986

Different in vitro generation of C3d by cuprammonium and polycarbonate capillary hemodialyzers.

Cellulosic membranes have been shown to activate C3 via the alternative pathway. Generation of the stable product C3d was compared in polycarbonate (PC) and cuprammonium (CU) hollow-fiber minidialyzers with identical geometry, using an in vitro recirculation system with platelet-poor plasma (recirculation rate 20 ml/min; 1,600 fibers; 0.115 m2; 40 ml system priming volume; recirculation time 120 min). After extensive washing, residual protein was removed by reverse transmembrane pressure (1.5 bar) from the air-filled dialysate compartment. Such protein fraction, functionally defined as 'secondary membrane', was similar in quantity for PC and CU fibers. Plasma proteins were present in the membrane without selective adsorption (flat-bed polyacrylamide gel electrophoresis and rocket immunoelectrophoresis using monospecific antibodies). C3d, measured by immunoelectrophoresis, increased with time in the fluid phase compartment of both dialysers, but C3d generation was consistently and significantly (p less than 0.05) less in PC than in CU dialysers. The observation documents an activation of C3 with PC, in contrast to previous reports of no activation. However, C3 activation with PC was less intense than with CU.

Adsorption↗
PubMed1985

Schistosoma mansoni: immunoblot analysis of adult worm proteins.

Proteins of adult Schistosoma mansoni were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and assayed in immunoblots for reactions with individual mouse sera. Four weeks after a heavy infection with a few hundred cercariae, IgG antibodies directed predominantly against a protein of 31 kDa were detected. The protein was only weakly recognized by antibodies of mice harboring a 4-week-old light infection with about 60 cercariae. After 6 weeks or more, mice infected with either dose formed antibodies, not only against the 31-kDa protein and a 67-kDa protein, but also against a number of other components. While reactions with the 31- and 67-kDa proteins occurred with sera of all individual mice of four different strains, the reactions with other components were less consistently observed. Mice vaccinated with a heavy or light dose of 20,000-rad-irradiated cercariae did not form antibodies detectable in the blotting system. However, in immunofluorescence assays with living skin schistosomula, but not lung schistosomula, antibodies against the larval surface were detected with all sera obtained 4 weeks after infection or vaccination. In addition, immunofluorescence studies using the same sera and sectioned adult parasites demonstrated the presence of antibodies against the parasite surface in all sera except those obtained from mice exposed to a light infection with normal cercariae. Mice infected in this latter way were the only animals that did not develop a significant resistance against a challenge infection 4 weeks after exposure to normal or irradiated cercariae. The presence of an immunofluorescent reaction against the schistosome gut always coincided with a reaction of the sera with the 31-kDa protein in the immunoblots. Although a role in immune resistance could not be ascribed to any of the proteins reacting in the immunoblots, the data demonstrate important differences in the antibody specificities induced by various infection schemes.

Animals↗
PubMed1985

The role of complement in inflammation.

The inflammatory process may be initiated by a great variety of stimuli. Amongst the diverse pathogenic pathways that lead from the primary stimulus to the tissue response, the serum complement system (C) seems the most important and, certainly, it is the best analyzed of the mediator systems.

Complement Pathway, Alternative↗
PubMed1985

Immunoblot analysis of Schistosoma mansoni antigens with sera of schistosomiasis patients: diagnostic potential of an adult schistosome polypeptide.

We compared the reaction in immunoblots of sera obtained from patients with parasitologically proven S. mansoni infections, with a suspected history of schistosomiasis infection, or with unrelated parasitic diseases. Several polypeptides from adult S. mansoni reacted with the schistosomiasis patients' sera in a heterogeneous manner. However, a component of approximately 31 kilo daltons (kD) reacted with all schistosomiasis sera and with several sera of suspected schistosomiasis cases. No reaction was ever observed with sera of patients harbouring other parasites. Thus, the polypeptide has potential diagnostic value. The use of sera of patients with recent infections demonstrated that: the earliest time of antibody formation against the 31 kD component was approximately 40 days post infection, the reaction with this polypeptide in immunoblots was exceptionally strong and antibodies directed against other schistosome proteins were barely detectable at this time. Identical results were obtained with sera of experimentally infected mice. The 31 kD component was present in parasites of either sex. It was apparently not a glycoprotein. Evidence suggests that the 31 kD polypeptide may originate from the schistosome gut.

Animals↗
PubMed1984

Schistosoma mansoni: escape from complement-mediated parasiticidal mechanisms following percutaneous primary infection.

Schistosomula were recovered from the skin of mice following primary infections. On the surface of such "infecting schistosomula", mouse C3 could not be detected by immunofluorescence. Subsequent incubation in vitro with fresh mouse serum led to the effective deposition of mouse C3 on schistosomula only when they were recovered within a few hours but not after one or two days following infection. In vitro deposited murine C3c was lost from i.v. injected schistosomula in the mouse circulation within one day as was human C3c. Infecting schistosomula exhibited a close to complete resistance to the lytic in vitro activity of human complement. This resistance was complete in older parasites. It existed in spite of the presence of parasite-bound human C9, which was detectable on all developmental stages of schistosomes following incubation in fresh, but not inactivated human serum. Lung schistosomula, 3-week and 6-week-old schistosomes were resistant to cellular cytotoxicity upon incubation with fresh human serum and rat peritoneal exudate cells although cell adherence mediated by human C3b was demonstrated with lung worms. The data suggest that schistosomula may evade in vivo the lytic activity of complement and also complement-mediated cellular cytotoxicity. Depending on the species of serum, this can be demonstrated in vitro by lack of opsonization or by resistance to lytic and cellular attack mechanisms.

Animals↗
PubMed1984

Schistosoma mansoni: loss of the ability of schistosomula to bind mouse complement following intravenous injection into mice.

The ability of freshly prepared schistosomula to become opsonized by the alternative pathway of mouse complement in vivo was investigated. Skin schistosomula were intravenously injected into mice and recovered shortly afterwards from their lungs. Following an in vivo residency of a few minutes, most schistosomula had considerably less C3b detectable by immunofluorescence on their surface than worms which had been incubated for the same time with mouse serum in vitro. Deposition of C3b was undetectable on all schistosomula following an in vivo residency of a few hours. Irradiation or treatment with puromycin of the schistosomula prior to injection did not alter the difference between in vitro and in vivo complement deposition. Moreover, schistosomula which had been passaged briefly through a mouse, lost most of their ability to deposit mouse complement on their surface during a subsequent in vitro incubation with mouse serum. It is suggested that opsonization of freshly transformed schistosomula with C3b of murine complement is less efficient in vivo than in vitro.

Animals↗