Biomedical subjects

M Schulze

Publications and source records attributed to M Schulze.

At least 91 records · Page 5Linked to original sources

PubMed1991

Urinary excretion of the C5b-9 membrane attack complex of complement is a marker of immune disease activity in autologous immune complex nephritis.

The urinary excretion of the C5b-9 membrane attack complex of complement correlates with glomerular deposition of antibody in the passive Heymann nephritis (PHN) model of membranous nephropathy (MN). To determine if this parameter can be correlated with antibody deposition in a model of MN induced by an autologous mechanism and thus more analogous to human MN, the relationship of urinary C5b-9 to ongoing glomerular immune complex formation late in autologous immune complex nephritis (AICN) was studied. Based on urinary C5b-9, the animals were divided into two groups at 12 weeks after induction of AICN, those with persistently high urinary C5b-9 excretion and those in whom urinary excretion of C5b-9 returned to undetectable levels. While all rats developed glomerular deposition of rat IgG and significant proteinuria, high C5b-9 excretors had greater proteinuria and prolonged positive staining for glomerular C3. When normal syngeneic kidneys were transplanted into rats (n = 3) from each group, only those with persistent C5b-9 excretion developed subepithelial immune deposits of rat IgG in the transplanted kidney. As in the PHN model of MN, proteinuria was dissociated widely from urinary C5b-9 excretion, glomerular C3 staining, and evidence of circulating antibody. Thus these findings demonstrate that urinary excretion of C5b-9 serves as an index of on-going immunologic disease activity in the AICN model of MN, while proteinuria does not.

Animals↗

PubMed1990

Regulation of the human autologous T cell proliferation by endogenously generated C5a.

The immunomodulating role of endogenously synthesized C5 and subsequently generated C5a was studied in a serum-free human autologous mixed leukocyte reaction (AMLR) using either separated T and non-T cell populations or unfractionated mononuclear leukocytes of human peripheral blood. Monoclonal mouse IgG or Fab fragments against human C5/C5a were used as probes for the evaluation of the biological effects of C5a. The reduction of DNA synthesis after the addition of nanogram amounts of anti-C5/C5a mAb was dose-dependent, reaching maximum levels of 30-50%. Of special importance was the availability of a mAb that recognizes a neoepitope present on C5a and not on serum-derived C5. The demonstration of the specificity of its inhibitory effect suggests that C5 is synthesized under the in vitro conditions employed and that the subsequently generated C5a exerts biological effects on T cell proliferation.

Antibodies, Monoclonal↗

PubMed1990

Increase of C-reactive protein serum values following haemodialysis.

In this study serum C-reactive protein values were measured to prove the induction of an acute-phase response during the haemodialysis procedure in end-stage renal disease patients. C-reactive protein values were measured with a sensitive enzyme-linked immunosorbent assay to detect values below the detection limit of standard assays. Predialysis C-reactive protein serum values in 17 patients on regular haemodialysis with cuprophan dialysers were greater than those of 18 normal controls (P less than 0.001). In the same group of haemodialysis patients serum C-reactive protein values 24 h after haemodialysis were significantly greater than predialysis values (P less than 0.001). These results suggest that acute-phase proteins are induced during haemodialysis, probably due to cytokine release during the haemodialysis procedure.

Adult↗

PubMed1990

[Detection of soluble fibrin monomer complexes by the netropsin precipitation test in childhood meningitis].

During a period of two years children with abacterial meningitis as well as bacterial meningitis were examined before treatment and later during disease. The new Netropsin praecipitation test according to Funke and coworkers was used to detect soluble fibrin monomer complexes. Only in a few cases of abacterial meningitis, but in the majority of cases with bacterial meningitis, a positive result had been shown. Excessive increase had been found in Waterhouse-Friderichsen syndrome. According to our results of coagulation tests we conclude 1. the ethanol gelation test is out-of-date, 2. the heparin treatment in bacterial meningitis is further indicated.

Child↗

PubMed1989

Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy.

Deposition of the C5b-9 complex of C in glomeruli of rats with experimental membranous nephropathy (MN) is essential for the development of proteinuria. In this investigation C5b-9 was localized in the passive Heymann nephritis (PHN) by immunoelectron microscopy with a mAb specific for C5b-9(m) neoantigen. Its distribution was compared with that in another model of MN induced by successive injections of cationic human IgG and rabbit anti-human IgG into rats. In PHN C5b-9 was found: 1) in the immune deposits (ID), and on the cell membranes of foot processes close to the ID; 2) in clathrin-coated pits of the glomerular epithelial cells (GEC) close to the ID and in membrane vesicles in the cytoplasm, separated from sheep IgG and the gp330 Ag; 3) in high concentration in multivesicular bodies of GEC; and 4) in association with membrane vesicles in the urinary space which presumably are the exocytosed content of membrane vesicular bodies. By contrast, in the cationic IgG-MN model C5b-9 was found mostly in ID, but rarely within the GEC. By freeze-fracture electron microscopy we have further identified 200- to 250-A intramembrane particles in PHN in the cell membranes of the "soles" of the foot processes which resemble membrane inserted human C5b-9(m). Degradation products of C5b-9 were further detected by immunoblotting of a 100,000 x g pellet of PHN rat urine. These results indicate that, in PHN, C5b-9 is inserted into the cell membranes of GEC, and that it is selectively endocytosed and transported across GEC by a cellular mechanism which apparently protects the cell from accumulation of membrane-inserted C5b-9.

Animals↗

PubMed1989

Accumulation of the cytochrome c oxidase subunits I and II in yeast requires a mitochondrial membrane-associated protein, encoded by the nuclear SCO1 gene.

The yeast nuclear SCO1 gene is required for accumulation of the mitochondrially synthesized cytochrome c oxidase subunits I and II (COXI and COXII). We cloned and characterized the SCO1 gene. It codes for a 0.9 kb transcript. DNA sequence analysis predicts a 33 kDa protein. As shown by in vitro transcription and translation experiments in combination with import studies on isolated mitochondria, this protein is matured into a 30 kDa polypeptide which is tightly associated with a mitochondrial membrane. The possible function of the SCO1 gene product in the assembly of cytochrome c oxidase is discussed.

Amino Acid Sequence↗

PubMed1989

Urinary excretion of C5b-9 reflects disease activity in passive Heymann nephritis.

Passive Heymann nephritis (PHN) is a model of membranous nephropathy in rats in which glomerular injury is mediated by the terminal C5b-9 membrane attack complex of complement. This model has been shown to be associated with markedly elevated urinary excretion of C5b-9, compared to other experimental models of glomerulonephritis To determine if urinary C5b-9 excretion could serve as an index of disease activity by correlating with the formation and quantity of glomerular subepithelial immune deposits in PHN, we measured urinary excretion of C5b-9 in PHN under several experimental conditions. In the heterologous phase a direct correlation was demonstrated between levels of urinary C5b-9 excretion and the amount of anti-Fx1A IgG deposited in glomeruli (r = 0.85). In the autologous phase, C5b-9 excretion correlated with the amount of deposit forming antibody present in the serum and resolved when antibody disappeared, despite persistence of glomerular deposits of antigen, antibody, C5b-9 and heavy proteinuria. Glomerular C3 deposits paralleled urinary C5b-9 excretion. Re-initiation of active deposit formation by a second injection of anti-Fx1A produced new C3 deposits and a marked rise in C5b-9 excretion. Finally, complete abrogation of deposit formation by transplanting PHN kidneys into normal recipients also halted C5b-9 excretion. Our findings demonstrate that urinary excretion of C5b-9 is a sensitive index of on-going immunologic disease activity in the PHN model of membranous nephropathy.

Animals↗

PubMed1989

Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis.

We have previously reported that both neutrophils (PMNs) and platelets mediate proteinuria in a model of subendothelial immune complex (IC) nephritis (GN) in the rat. In order to understand the interaction of PMNs and platelets in this model, we quantitated the uptake of 111In-labelled platelets in glomeruli and correlated this with the number of PMNs observed histologically at 10 and 30 minutes, 1, 4 and 24 hours following induction of GN. Platelet accumulation was biphasic with a major peak at 10 minutes and a minor peak at four hours. Early platelet accumulation was complement dependent, and PMN-independent. PMN accumulation occurred after the initial platelet influx, peaking at one and four hours, was complement dependent, but was not affected by platelet depletion. Complement depletion significantly reduced proteinuria. This is the first documentation that platelet accumulation in glomeruli in IC GN is complement dependent. In addition, the enhancement of PMN-mediated injury by the platelet in this model does not involve effects of platelets on PMN localization, thus implying a functional interaction between these cells within the glomerulus.

Animals↗

PubMed1989

Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis in the rat.

Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis from other forms of experimental glomerulonephritis in the rat. In the passive Heymann nephritis (PHN) model of membranous nephropathy (MN) subepithelial deposits form from anti-Fx1A antibody reacting with antigen expressed on the glomerular epithelial cell membrane followed by membrane patching and shedding of immune complexes. Immune complex deposits are accompanied by deposits of C5b-9 which is required for the mediation of proteinuria. We tested the hypothesis that C5b-9 assembly on the epithelial cell membrane might result in C5b-9 excretion in the urine, which would distinguish this autoimmune mechanism of MN from other processes that result in subepithelial immune complex deposits. Using monoclonal antibodies developed to rat C6 and a rat C5b-9 neoantigen, in a sensitive ELISA assay, elevated urinary excretion of rat C5b-9 was documented in PHN associated with on-going glomerular immune deposit formation. No urinary C5b-9 was detectable in MN induced by an exogenous antigen (cationized IgG) despite equivalent glomerular C5b-9 deposits, or in models of nephrotoxic nephritis, subendothelial immune complex nephritis, anti-mesangial cell membrane antibody-induced nephritis or two non-immune nephropathies. Infusion of preformed C5b-9 in proteinuric animals excluded glomerular filtration of C5b-9 as a contributing mechanism to urinary C5b-9 excretion. We conclude that in the rat, increased urinary excretion of C5b-9 is a marker of MN induced by antibody to a glomerular epithelial cell antigen. Urine C5b-9 excretion reflects active glomerular immune deposit formation and distinguishes MN induced by this mechanism from other forms of MN as well as from other glomerular diseases with equivalent glomerular C5b-9 deposits.

Animals↗

PubMed1989

Comparative study of C5a plasma levels with different hemodialysis membranes using an enzyme-linked immunosorbent assay.

Using a specific and sensitive ELISA for C5a, the present study shows that predialysis levels of C5a in end-stage renal disease patients are not elevated and that all membranes studied (Cuprophan, Hemophan, Gambrane and hydrophilic polysulfone) cause significant increases of C5a plasma levels albeit to different degrees. Higher increases of C5a were accompanied by larger decreases of circulating granulocytes and monocytes. Dialyzers with a newly introduced modified regenerated cellulose membrane, Hemophan, showed lower C5a plasma levels during hemodialysis than Cuprophan. With Hemophan C5a plasma levels were comparable to those with polysulfone membranes.

Adult↗

PubMed1989

[Quantitative acetylcholinesterase (AChE)--determination in amniotic fluid--potential for differential diagnosis in consistently high AFP levels during general AFP screening for prenatal diagnosis of open neural tube defects].

Measurement of maternal serum alpha-fetoprotein concentration for prenatal detection of open neural tube defects had been introduced into the obstetrical care of pregnant women in the district of Schwerin since 1983. In cases of high risk for presence of an open neural tube defect, noticed by elevated levels of maternal serum alpha-fetoprotein concentration step by step further diagnostic steps are necessary. In addition to special examination by ultrasound and measurement of alpha-fetoprotein concentration in amniotic fluid quantitative analysis of acetylcholinesterase activity in amniotic fluid seems to be valuable. Reliability of detecting open neural tube defects in prenatal care had been proved by quantitative analysis of acetylcholinesterase activity in amniotic fluid. The existing results up to now were very reliable, especially biological transit stages from normal to pathological findings were taken into consideration, too. In these cases further controls are necessary. Levels of acethylcholinesterase activity below the 90th percentile can be considered as normal findings, levels above the 99th percentile must be interpreted as pathological findings. These are our experiences up to date.

Acetylcholinesterase↗

PubMed1989

[Frequency of hypoxic episodes during general anesthesia in children].

We measured the frequency and extent of arterial hypoxemia during pediatric general anesthesia under routine clinical conditions. The subjects were 91 children (13 newborns, 27 infants, 37 children under 6 years, 14 children under 14 years) with normal heart and lungs scheduled for extrathoracic surgery. Mask anesthesia (spontaneous/assisted ventilation) was performed in 30 cases, endotracheal anesthesia (controlled ventilation) in 61 cases. Arterial oxygen saturation (SaO2) was determined by pulse oximetry at entry into the operating room and recorded continuously from induction of anesthesia to emergence. Hypoxic episodes (minimum duration: 30 s) were classified as slight (SaO2 less than or equal to 95%), minor (SaO2 less than or equal to 90%) and major (SaO2 less than or equal to 85%). The data were analyzed with the Fisher's test. 52% of all children experienced at least one hypoxic episode. Frequency and extent of hypoxic episodes decreased as age and weight of the children increased. Major hypoxic episodes occurred in 54% of the newborns, 26% of the infants, 8% of the children under 6 and 7% of the children under 14. A body weight of 10 kg appeared to constitute a threshold: in children below this weight arterial oxygen desaturation occurred significantly more frequently (p less than 0.001), and the incidence of major episodes was significantly higher (p less than 0.005). Major episodes were almost evenly distributed between induction and awakening from anesthesia, only one episode occurred during maintenance. Desaturation was more likely to occur in intubated children than in those with a mask (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Depletion of C6 prevents development of proteinuria in experimental membranous nephropathy in rats.

To study the possible role of the complement membrane attack complex, C5b-9, in an experimental rat model that is morphologically indistinguishable from membranous nephropathy in man (passive Heymann nephritis [PHN]), an antibody to rat C6 was used to deplete C6 levels to less than 5% of pretreatment values (C6D) during disease development. C3, C7, C8, and C9 levels were not different in C6D and control rats. After injection of nephritogenic quantities of 125I-anti-Fx1A antibody, the kinetics of disappearance of labeled IgG from the blood were identical in the complement deficient and sufficient groups, and glomerular deposition of 125I-antibody was the same in both groups at 5 days. Glomerular deposits of sheep IgG and C3 were also similar in C6D and controls, but glomerular deposits of C6 and C5b-9 neoantigens were markedly reduced or absent in C6 depleted rats. However, despite equivalent antibody deposits, proteinuria was abolished in C6D rats compared with normocomplementemic controls. Similar results were obtained when F(ab')2 anti-rat C6 IgG was used to deplete C6 during development of PHN. These results demonstrate that C6 is required for the development of the increased glomerular permeability that occurs in PHN, presumably because C6 is required for formation of C5b-9. We conclude that glomerular injury in the PHN model of membranous nephropathy in the rat is mediated by C5b-9.

Animals↗

PubMed1988

The human neutrophil serine proteinases, elastase and cathepsin G, can mediate glomerular injury in vivo.

We infused microgram quantities of active or inactive PMN elastase and cathepsin G into the renal arteries of rats. Both active and inactive elastase localized to the glomerular capillary wall equally, and in amounts that could be achieved physiologically in GN. However, elastase-perfused rats developed marked proteinuria (196 +/- 32 mg/24 h) compared with control rats receiving inactive elastase (19 +/- 2 mg/24 h, p less than 0.005). Similar results were seen with active and inactive cathepsin G. Neither elastase nor cathepsin G infusion was associated with histologic evidence of glomerular injury. We conclude that the PMN neutral serine proteinases elastase and cathepsin G can mediate marked changes in glomerular permeability in vivo due to their proteolytic activity, and thus, may contribute to the proteinuria observed in PMN-dependent models of GN.

Animals↗

PubMed1988

SCO1, a yeast nuclear gene essential for accumulation of mitochondrial cytochrome c oxidase subunit II.

We have identified and isolated a novel yeast nuclear gene (SCO1) which is essential for accumulation of the mitochondrially synthesized subunit II of cytochrome c oxidase (CoxII). Analysis of the mitochondrial translation products in a sco1-1 mutant reveals a strong reduction in CoxII. Examination of mitochondrial transcripts by Northern blot hybridization shows that transcription and transcript maturation of OXI1, the gene coding for CoxII, is not affected. Therefore the SCO1 gene product must be involved in a post-transcriptional step in the synthesis of CoxII. We have isolated a 1.7 kb DNA fragment from a yeast gene bank which carries the functional SCO1 gene. Two RNA species of 0.9 kb and 1.2 kb, respectively, hybridize with this DNA fragment, which is localized on chromosome II. Cells whose chromosomal 1.7 kb fragment has been replaced by the yeast URA3 gene fail to accumulate CoxII and in addition subunit I of cytochrome c oxidase (CoxI). The possibility that the SCO1 gene product is bifunctional, i.e. required for both CoxI and CoxII accumulation, is discussed.

Cell Nucleus↗

PubMed1988

Correlation between the alpha 1-fetoprotein (AFP) concentrations determined in the sera and in the tumour tissues in patients with testicular tumours.

AFP was determined simultaneously in the sera and in the tumorous tissues of 10 patients with testicular tumour. Two seminomas proved to be negative with two methods. Out of the 8 non-seminomas 7 showed increased serum levels and AFP was detectable in the tumour tissues of 6 patients. Staining of AFP in the testicular tumour tissue with an indirect immunoperoxidase reaction has achieved clinical significance only in cases of metastases of unknown primary tumours or of extragonadal germinal cell tumours.

Dysgerminoma↗

PubMed1988

Platelets mediate neutrophil-dependent immune complex nephritis in the rat.

Neutrophils and platelets are frequently present in glomeruli in immune glomerulonephritis (GN). No role for the platelet in acute neutrophil-mediated renal injury has been defined. We investigated a neutrophil-mediated model of subendothelial immune complex GN in the rat. Rats were platelet-depleted (mean platelet less than 10,000/microliter) with goat anti-platelet IgG before induction of GN by the renal artery perfusion of concanavalin A followed by anti-concanavalin A IgG. Platelet-depletion resulted in a significant reduction in albuminuria (7 +/- 2 vs. 55 +/- 10 mg/24 h) and fractional albumin excretion (0.045 +/- 0.01 vs. 0.410 +/- 0.09) compared with controls. The decrease in albuminuria was not due to differences in blood or glomerular neutrophil counts, complement, renal function, or glomerular antibody binding. Platelet-depleted rats had equivalent subendothelial deposits and glomerular endothelial cell injury but had minimal platelet infiltrates and fibrin deposition compared with controls. These studies demonstrate a role for platelets in mediating acute neutrophil-induced glomerular injury and proteinuria in this model of GN.

Animals↗

PubMed1988

[Prenatal detection of open neural tube defects in a mass screening program by determination of alpha-fetoprotein concentration in maternal serum].

A partially automatized ultramicroencymimmunoassay developed by the GDR and Cuba should be tested in a mass screening for the prenatal detection of open neural tube defects by measurement of maternal alphafetoprotein concentration (MS-AFP). In the screening program 24,271 pregnant women were included (Berlin/District of Schwerin). In 18,144 patients AFP-concentration in maternal serum was measured as a routine procedure in the care for all pregnant women of the district of Schwerin. The time of MS-AFP determination in this connection was limited from 15th to 18th completed gestational week. 1986 already in 84.9 per cent of all pregnant women of the district of Schwerin MS-AFP concentration could be measured in early pregnancy. The detective rate of open neural tube defects among 24,271 tested pregnant women was 86.1 per cent. AFP concentration was expressed in ng/ml and the "cut off" was set at 2.0 MOM. Infants born with open neural tube defects were reduced by 75 per cent under the conditions of MS-AFP screening. Better results are possible in connection with a progress in the qualification of the following diagnostic steps, if MS-AFP-levels are elevated. Not unexpected and unspecific MS-AFP-elevation was found in connection with twin pregnancies and a higher risk of abortion and the delivery of infants with very low birth-weight less than 1,500 g. A general MS-AFP-screening is recommended for prenatal detection of open neural tube defects all over the country.

Anencephaly↗