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Biomedical subjects

W Mondorf

Publications and source records attributed to W Mondorf.

At least 19 recordsLinked to original sources

Carbon disulphide. III. Risk factors for coronary heart diseases in workers in the viscose industry.

To evaluate risk factors for coronary heart disease and factors which can influence the course of acute myocardial infarction in workers exposed to CS2 we performed a cross-sectional study of 247 workers in the viscose industry. The control group of 222 men from the same plant was comparable for age, social status and physical work. The CS2 exposure determined by personal air sampling ranged from < 0.2 ppm to 65.7 ppm (median: 4.0 ppm) and the duration of exposure ranged from 4 to 220 (median: 66) months. Using a multiple linear regression model we found neither higher blood pressure at rest or after exercise, nor hyperlipoproteinaemia in a higher degree, nor lower high-density lipoprotein (HDL) or lower apolipoprotein A-I levels, nor higher blood glucose values, nor indicators of direct cardiotoxic effects or signs of disturbances in blood coagulation in the exposed group in comparison to controls. Regarding the influence of chronic exposure on the investigated parameters, we found an inverse correlation of the cumulative exposure (mean CS2 exposure in the department multiplied by the duration of work in this department) with the HDL concentration. The HDL levels correlated with the duration but not with the intensity of exposure. In the same way the apolipoprotein A-I levels showed a negative association with the duration of exposure in the exposed group as well as in the control group. The HDL concentrations showed the same trend for the controls. It therefore seems that this finding is more likely due to confounding factors than to the CS2 exposure. As all subjects (exposed and controls) have done shift work, in some cases for a long time, this kind of work could be responsible for the negative relationship between the duration of employment as a shift worker and the apolipoprotein A-I and HDL levels. At the current air-borne levels no significant differences were found between the exposed persons and the controls in the distribution frequency for blood pressure values, lipoproteins, blood glucose, blood coagulation and indicators of direct cardiotoxic effects.

Adult

Screening of F.VIII:C antibodies by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (Elisa) method was developed in order to examine prevalence and titer of antibodies directed against the factor VIII coagulant protein (F.VIII:C) in hemophilia A and nonhemophilia A patients. Highly purified F.VIII:C was used as immunosorbent on microtiter plates with a peroxidase-conjugated goat anti human IgG antibody for F.VIII:C antibody detection. Results determined by Elisa were compared with measurements according to the Bethesda method. Initially 24 plasma samples containing an F.VIII:C inhibitory activity ranging from 0 to 7,700 Bethesda units (BU) were analysed. At plasma dilutions of 1:128 the optical density determined by our Elisa measurement and the corresponding BU showed a logarithmic correlation. The coefficient of correlation was r = 0.92 with a standard deviation of 0.002 from the regression curve. Plasma samples were analysed from 53 hemophilia A patients, from 21 nonhemophilia patients with acquired F.VIII:C antibodies and from 460 randomly selected nonhemophilia patients presenting for routine preoperative coagulation examination. F.VIII:C antibody-positive Elisa results and positive BU were found in 7 hemophilia A patients and the 2 patients with a history of acquired F.VIII:C antibodies. Positive Elisa results and negative BU were found in 1 hemophilia A patient and 25 out of 460 nonhemophilia A patients (5.43%) suggesting F.VIII:C antibodies without inhibitory potency on F.VIII:C in these cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Characterization of the gene for apolipoprotein E5-Frankfurt (Gln81->Lys, Cys112->Arg) by polymerase chain reaction, restriction isotyping, and temperature gradient gel electrophoresis.

A new apolipoprotein (apo) E variant, apoE5-Frankfurt, was identified in a 43-year-old male with moderate hypercholesterolemia. On isoelectric focusing in an immobilized pH gradient, apoE5-Frankfurt migrated to a position more cathodic than apoE4 (Cys112->Arg). On sodium dodecyl sulfate-gel electrophoresis, its apparent molecular weight could not be distinguished from that of the three common apoE isoforms (E2, E3 and E4). Restriction isotyping with CfoI (HhaI) showed that apoE5-Frankfurt had arginine in positions 112 and 158 of the mature protein, suggesting that the mutation accounting for the additional positive charge had occurred in an epsilon 4 allele. The third and the fourth exon of the apoE gene were amplified using the polymerase chain reaction and analyzed by temperature gradient gel electrophoresis. This suggested that there were two mutations in the fourth exon of the mutant allele. Cloning and sequencing disclosed that, apart from the exchange of arginine for cysteine in position 112, a C to A substitution replaced glutamine (CAA) in position 81 by lysine (AAA).

Adult

Quantitative enzymatic and immunologic computer-assisted histophotometry of human kidney tissue following neoplastic and other clinically significant alterations.

Renal tissue sections from 178 patients, whose kidneys were either normal or altered by various conditions such as hydronephrosis, interstitial nephropathies, chronic graft rejection, renal cancer etc., were investigated by computer-assisted histophotometry. We used enzyme histochemical and immunologic methods to measure kidneys suffering from various urological diseases quantitatively. Through this procedure, we were able to obtain information that allowed us to determine the degree of alteration in the metabolic state of tubular epithelial cells. The tissue activities of the following enzymes of the proximal tubule were investigated: alanine aminopeptidase (AAP), alkaline phosphatase (AP) and maltase (Ma) as membrane-bound markers, and beta-glucuronidase (beta-Gl) as a lysosomal marker. In addition, AAP and gamma-glutamyltranspeptidase (GGTP) were measured by immunofluorescent microscopy after having added specific anti-enzyme antibodies to the tissue sections. Compared to normal kidneys, quantitative enzyme histograms of diseased kidneys revealed a significant decrease in marker protein concentration of the tubule. The decline in tissue enzyme activities of AP, AAP, Ma and beta-Gl was accompanied by a significant decrease of enzyme concentrations as measured by the immuno histological method. This was especially true in cases with kidney cancer and in kidney tissues adjacent to infiltration adenocarcinoma. Morphological analyses of alterations were generally improved by enzymatic and/or immunologic histophotometry.

Adenocarcinoma

[Quantitative enzymatic and enzyme histochemical analysis in detecting inductive and nephrotoxic effects of various antibiotics].

In order to evaluate quantitatively changes of kidney tubular membrane and lysosomal proteins following administration of aminoglycosides and cephalosporins enzymatic and enzyme histochemical investigations were performed. Alterations of kidney enzyme concentrations of the proximal tubule were considered as a parameter indicating nephrotoxic and inductive effects of antibiotics. Following administration of aminoglycosides to volunteers significantly (Wilcoxon test, 2P less than 0.05) increased enzymuria was found as compared to untreated control persons. Under experimental conditions inductive effects were analysed following treatment with aminoglycosides, especially gentamicin. In contrary to these findings cephalosporins were administered without effects an the proximal tubule. Once daily administration of aminoglycosides were observed to be less nephrotoxic than twice daily injections to volunteers. Quantitative evaluation of tubular specific proteins appears to be a tool in monitoring the degree of alterations (enzyme induction, -liberation, -excretion) caused by antibiotics.

Aminoglycosides

Quantitative histophotometry analysing significant inductive and alterative effects of aminoglycoside application (gentamicin, tobramycin, amikacin) upon tubular kidney proteins.

In order to evaluate quantitative changes in kidney proteins, computer-assisted histophotometry of tissues was performed. Kidney marker enzyme concentrations were considered to be involved in inductive and alterative developments in the proximal tubule. These effects were caused by the administration of aminoglycosides. Indicator enzymes of the proximal tubule such as membrane-bound alkaline phosphatase (AP) and alanine-aminopeptidase (AAP) as well as lysosomal beta-glucuronidase (beta-Gl) were stained in kidney tissues. Graphic monitoring and digital display of kidney cortex sections were registered by electronic image analysis using the 'Micro-Videomat' 2 system. As an experimental design, 160 kidneys of Wistar rats were studied. Their kidneys were analyzed after one, two and three intravenous applications of gentamicin, 25 mg/kg/day, or tobramycin, 25 mg/kg/day, or amikacin, 50 mg/kg/day, on consecutive days. In a fourth test group, the kidneys were examined after the third application and a 5-day recovery period. Concentrations of tubular marker enzymes were significantly increased (2p less than 0.01, Wilcoxon test) after two applications of gentamicin: AP 37.6%, AAP 6.3% and beta-Gl 11.8%. Contrary to these findings, after two injections of tobramycin or amikacin only slight alterations were documented: tobramycin, AP 14.5%, AAP -0.1% and beta-Gl 0.4%; amikacin, AP 6.0% and AAP 4.2%. The studies indicate that tobramycin induces less severe nephrotoxic and inductive reaction than gentamicin and partly than amikacin in doses administered during our experiments. In all cases, enzyme activities studied were nearly normalized after three applications of aminoglycosides and a recovery period of 5 days. Quantitative computer-assisted evaluation of the proteins located in the tubule appears to be a tool for monitoring the degree of alterations caused by enzyme induction, enzyme release and excretion of kidney proteins.

Alkaline Phosphatase

Effect of a proteinase inhibitor, aprotinin, on brush border membrane associated aminopeptidase of human kidney cortex.

In order to study the influence of the basic proteinase inhibitor aprotinin (Trasylol) on renal tubular alanine-aminopeptidase (E.C.3.6.11-), a brush border fraction was prepared from human kidney cortex by differential centrifugation. Incubation of brush border fragments, rich in membrane bound alanine-aminopeptidase, resulted in an activation of the enzyme. However, aminopeptidase, which was cleaved off from the membranes by limited proteolysis and subsequently purified by Concanavalin A-affinity chromatography exhibited activation by low but inhibition by higher concentration of aprotinin. Thus inhibition was associated with presence of the solubilized form of the brush border enzyme. On the other hand, as was shown by quantitative electroimmunoassay, formation of antigen-antibody complexes between soluble renal aminopeptidase and its specific rabbit antibody was not changed by the basic polypeptide.

Aminopeptidases

Isolation of kidney brush border gamma-glutamyl transpeptidase from urine by specific antibody gel chromatography.

The IgG fraction of antiserum directed against gamma-glutamyl transpeptidase (gammaGTP, EC 2.3.2.2) isolated from human kidney brush border membranes after limited proteolysis, was covalently bound to cyanogen bromide-activated Sepharose. With this antibody-gel, gammaGTP present in the urine of patients as a result of tubular damage was immunospecifically prepared by affinity chromatography. The enzyme isolated from the urine samples gave a complete cross-reaction wiht gammaGTP artificially cleaved off from brush border fragments. Since labelled anti-gammaGTP sera gave a specific immunofluorescence only of the luminal portion of cortical tubule, the use of immunosorption chromatography appears to be an important approach for the isolation of urinary kidney tissue antigens of a defined origin.

Cell Membrane

Decreased tuftsin concentrations in patients who have undergone splenectomy.

Serum tuftsin concentrations were measured, using a radioimmunoassay developed in Israel, in normal subjects and in patients who had undergone splenectomy. Concentrations in those who had undergone traumatic and elective splenectomy were much lower. The tuftsin concentration in 38 patients with Hodgkin's disease who had undergone splenectomy during staging laparotomy was not significantly different from the mean concentration in other patients who had had elective splenectomy. In four patients who underwent splenectomy for non-malignant haematological disorders measurements made before and after operation showed that tuftsin concentrations fell significantly in the days after operation. The increased susceptibility to overwhelming infections of patients with Hodgkin's disease and others who have undergone splenectomy may be related to the low tuftsin concentrations. As pre-splenectomy tuftsin concentrations in patients with Hodgkin's disease were normal, the practice of performing staging laparotomy and splenectomy in patients with Hodgkin's disease should perhaps be reconsidered.

Adult