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Biomedical subjects

K Baumann

Publications and source records attributed to K Baumann.

At least 73 records · Page 4Linked to original sources

Binding of lysozyme to brush border membranes of rat kidney.

The binding of 125I-labelled egg-white lysozyme to isolated brush border membranes of rat kidney cortex was investigated. The lysozyme binding was reversible and saturable. The Scatchard plot revealed a one-component binding type with a dissociation constant of 7.8 microM and 15.6 nmol/mg membrane protein for the number of binding sites. The binding of the basic lysozyme could be reduced by basic amino acids such as L-lysine, L-ornithine or L-arginine, while neutral amino acids such as L-citrulline or L-alanine had no effect. The inhibitory effect of lysine was competitive.

Animals↗

Renal handling of endogenous lysozyme in the rat.

Quantitative studies of endogenous lysozyme (low molecular weight protein) were performed in rats. Urine and plasma concentrations of lysozyme and inulin were measured spectrophotometrically. An improved lysozyme assay (standard curve established by using egg white-lysozyme) enabled us to determine the mean plasma concentration of endogenous lysozyme (4.4 micrograms X ml-1) and the urinary concentrations of endogenous lysozyme (between 0.1 and 3.8 micrograms X ml-1. The urinary concentrations of endogenous lysozyme were found to be dependent on urinary flow rate. High urinary concentrations (ULy) were found at low urinary flow rates (V). The excreted amount of endogenous lysozyme (ULy X V) was independent of urinary flow rate and yielded a constant value of 0.02 micrograms X min-1. Mean glomerular filtration rate (GFR) was 1.2 ml X min-1 while clearance of endogenous lysozyme averaged 0.0039 ml X min-1. Inhibition of endogenous lysozyme reabsorption by cytochrome c was used to estimate the glomerular sieving coefficient of endogenous lysozyme in clearance experiments. CLy/GFR increased from a mean value of 0.0053 in control rats to 0.8 at maximal inhibition of tubular reabsorption of endogenous lysozyme by cytochrome c. Knowing the glomerular sieving coefficient, GFR and the lysozyme concentrations in plasma and urine samples, the filtered, excreted and reabsorbed lysozyme amounts could be calculated: 0.5% excreted and 99.5% reabsorbed. Reabsorbed endogenous lysozyme is stored in the kidney in high amounts (1,983 micrograms X g-1 kidney).

Absorption↗

Selective determination of the activities of neutral and acid alpha-glucosidase using discontinuous assays.

Most biological fluids contain both neutral and acid alpha-glucosidase. Optimal conditions were therefore developed for the selective determination of the activity of neutral and acid alpha-glucosidase, using 2-step, discontinuous assays. In the first step of the assay of neutral alpha-glucosidase, glucose was liberated from maltose (citrate-phosphate buffer, pH 6.8, 20 mmol/l maltose, 25 mmol/l turanose). Under these incubation conditions, turanose inhibited the residual activity of acid alpha-glucosidase almost completely without influencing the activity of neutral alpha-glucosidase. In the first step of the acid alpha-glucosidase assay, glucose was liberated from maltose (citrate-phosphate buffer, pH 3.8, 50 mmol/l maltose, 2 mol/l potassium chloride). Under these incubation conditions, potassium ions stimulate the activity of acid alpha-glucosidase and simultaneously inhibit almost completely the residual activity of neutral alpha-glucosidase. In the second step of the assay of neutral and acid alpha-glucosidase, the liberated glucose was measured by hexokinase/glucose-6-phosphate dehydrogenase. The effect of turanose and potassium ions on neutral and acid alpha-glucosidase from human urine was characterized.

Glucose↗

Excretion of neutral alpha-glucosidase, determined with a continuous assay, and of acid alpha-glucosidase in the urine of human reference subjects.

The catalytic activities of neutral and acid alpha-glucosidase were selectively determined in human urine. Urinary excretion of neutral and acid alpha-glucosidase in reference subjects was found to be in the range 1.61 to 20.36 microkat/mol creatinine and 7.47 to 33.60 microkat/mol creatinine, respectively. Urinary excretion of both enzymes was not related to sex, age or diuresis. A continuous assay was introduced to improve the determination of neutral alpha-glucosidase.

Age Factors↗

Nephrotoxicity of cis-diamminedichloroplatinum with or without ifosfamide in cancer treatment.

cis-Diamminedichloroplatinum (DDP) and ifosfamide (IPP) are effective cytostatic agents with a considerable nephrotoxicity. Because of the known synergism of both drugs in animals the combination has been studied in man with disseminated testicular cancer. Nature and extent of nephrotoxicity of DDP in combination with vinblastine, bleomycin and with or without IPP was investigated. The renal involvement was studied during volume expansion and mannitol diuresis. In addition to total kidney function (creatinine clearance and renal electrolyte handling), tubular function has been determined by quantitative assessment of urinary albumin, beta 2-microglobulin, maltase and leucine aminopeptidase excretion. The urinary protein pattern was also analyzed by microgradient electrophoresis to determine low and high molecular weight proteins. The total protein excretion was raised in the groups of patients with DDP and IPP to a 5-fold of the normal (976 +/- 96 mg/24 h) versus a 4-fold increase (756 +/- 102 mg/24 h) without IPP. This was mainly due to renal tubular involvement. For example, IPP raised the tubular toxicity induced by DDP considerably with a 200-fold increase of the beta 2-microglobulin excretion versus only a 10-fold increase without IPP (p less than 0.02). All lesions were reversible and caused no lasting impairment of kidney function. It is concluded that combination regimens including DDP and IPP can be used without a major risk of acute or chronic renal insufficiency. However, urinary protein excretion should be monitored to make certain that the tubular function improves between or after the treatment courses.

Albuminuria↗

Early nephrotoxicity at high plasma concentrations of lysozyme in the rat.

In clearance experiments, egg white lysozyme was intravenously infused into male Wistar and Wistar/Furth rats over different periods of time to achieve plasma concentrations of lysozyme in the range of 30 to 8000 micrograms per ml. The glomerular filtration rate and the appearance of glomerular and tubular epithelia were comparable to those of control rats below 3000 micrograms per ml. of plasma concentration of lysozyme and up to 60 minutes' infusion time when investigated by scanning electron microscopy. A 50 per cent drop in blood pressure occurred at a plasma lysozyme concentration of 3000 micrograms per ml., which could be prevented by the intravenous injection of an antihistamine or by using Wistar/Furth rats; however, the decrease of the glomerular filtration rate and of the fractional lysozyme reabsorption as well as the increase in sodium and potassium excretion could not be avoided. After 30 minutes of lysozyme infusion, the epithelial foot processes exhibited slight regional effacement, and in more than 50 per cent of the tubules protein cast formation was noted. Occurrence of foot process effacement and tubular casts increased with further increase of plasma lysozyme concentration and lysozyme infusion time. These morphologic changes were common for Wistar rats, antihistamine-pretreated Wistar rats, Wistar/Furth rats, and in situ-perfused rat kidneys. These results indicate that the cationic low molecular weight protein lysozyme induced functional and structural alterations that were correlated with plasma lysozyme concentration and lysozyme infusion time and caused acute renal failure.

Acute Kidney Injury↗

Occupational exposure to hexachlorocyclohexane. IV. Sex hormone alterations in HCH-exposed workers.

In a lindane (gamma-hexachlorocyclohexane)-producing factory 54 male workers (mean age 40 years, mean duration of exposure 8 years) were studied with regard to their blood levels of testosterone, LH, and FSH. Twenty clerks of nearly the same age were examined for control purposes in the same way. Serum-LH concentrations of the exposed workers were significantly higher than in controls. Geometric mean values were 8.8 mIU/ml and 5.7 mIU/ml respectively. On the other hand, FSH levels were insignificantly higher. Concerning testosterone concentrations in serum, these were found to be slightly lower in the group of workers than in control persons but this difference could not be proved to be statistically significant. These results indicate certain perturbations in sex hormone regulation probably as a consequence of HCH-exposure. To judge the pathological significance of these alterations further investigation will be necessary.

Adult↗

Occupational exposure to hexachlorocyclohexane. II. Health conditions of chronically exposed workers.

Sixty male workers in a lindane (gamma-hexachlorocyclohexane)-producing factory were examined with regard to health in comparison with an external control group of 20 clerks. Case history, physical examination, neurologic status, and ECG revealed no significant differences between groups. However, the following significant differences in clinical-chemical blood tests were ascertained: higher polymorphonuclear leukocyte count, lower lymphocyte count, higher reticulocyte count, lower prothrombin (Quick's) test, and lower blood concentrations of creatinine and uric acid. No significant differences were observed in total red and white blood cell as well as platelet counts, hemoglobin content, the other counts of differential blood picture, gamma-GT, GOT, GPT, LDH, cholinesterase, triglycerides, cholesterol, and urea. In spite of a pronounced exposure to the alpha-, beta-, and gamma-isomers of hexachlorocyclohexane, no signs of severe impairment of health were observed; only small deviations in some laboratory tests were found having no pathologic significance. However, biological monitoring and health supervision of HCH-exposed workers should be carried out.

Adult↗

Inhibition of renal accumulation of lysozyme (basic low molecular weight protein) by basic proteins and other basic substances.

Together the two rat kidneys accumulated a total of 31.7 +/- 1.6% of the intravenously injected amount of 7 nmoles egg-white-lysozyme (measured as iodine 125 lysozyme) within 10 min. The low molecular weight protein lysozyme and other basic substances were injected simultaneously in order to evaluate whether these basic substances can inhibit the renal lysozyme accumulation. The inhibitory effect of various basic compounds was dose-dependent with a maximal reduction of lysozyme accumulation to 11.7 +/- 0.08%. The basic substances could be divided into three groups depending upon the micromolar amount injected at which a 50% inhibition was achieved (0.3-1.2 micromoles: cytochrome C, ribonuclease; 10.9 micromoles; spermine; 501-688 micromoles: L-arginine, L-lysine). The neutral myoglobin had no effect on renal lysozyme accumulation. The inhibitory potency appeared to increase with increasing molecular weight and pI value of the substance tested. Microperfusion experiments of proximal convoluted tubules of rat kidney revealed that luminal reabsorption of the basic lysozyme can be inhibited by the basic protein cytochrome C in a dose-dependent fashion. In these experiments the perfusion solution contained 57 micromol .l-1 lysozyme, an intratubular lysozyme concentration at which the tubular lysozyme reabsorption was found to be about 80% saturated. A 50% inhibition of the tubular endocytic lysozyme reabsorption was achieved a cytochrome C concentration of 102 micromol.l-1.

Animals↗

Occupational exposure to hexachlorocyclohexane. I. Body burden of HCH-isomers.

In a lindane (gamma-hexachlorocyclohexane = gamma-benzenehexachloride)-producing factor 57 workers were studied with regard to their blood levels of the three hexachlorocyclohexane isomers: alpha-, beta-, and gamma-HCH. The TLV-TWA (MAK value 1979) for gamma-HCH of 0.5 mg/m3 was not exceeded at any of the workplaces where HCH is synthesized and purified to lindane. Additionally, in some of the workers samples of s.c. adipose tissue were taken for determination of HCH-isomer content. An external group of 20 clerks was examined in the same way for control purposes. In contrast to the control persons, none of whom had HCH-concentrations in serum above the respective detection limits, the values determined in serum of the exposed workers were in the following ranges: alpha-HCH: 10-273 microgram/1, beta-HCH: 17-760 microgram/l, and gamma-HCH: 5-188 microgram/1. Of special interest is the observation of a significant increase of beta-HCH-concentration in serum with the time of employment in lindane production, indicating a pronounced accumulation of this substance in the human organism. Concentrations of this isomer in s.c. adipose tissues were about 300-fold higher than in serum. A significant correlation between both parameters could be established. The results of this study show that adherence to the TLV-TWA of gamma-HCH is not sufficient for control of HCH-exposure. Furthermore, biological monitoring of exposed workers is necessary taking into account the three more important isomers alpha-, beta-, and gamma-HCH.

Adipose Tissue↗

Volume of brain ventricles in man determined by computer tomography.

In order to measure the absolute ventricular volumes in ml we developed a method using the numerical prints of CT (EMI, CT 1000) on which--by comparing with corresponding Polaroid photos--the margin between brain tissue and ventricles was drawn. For further evaluation, a curve digitizer and a digital computer were used. In 51 patients without any abnormal findings in CT, we studied the volume of single ventricles. The mean value of the whole ventricular system was 30.9 +/- 5.7 ml. Reproducibility by this method is within a range of 5%.

Cerebral Ventricles↗

The mechanism of action of harmaline on renal solute transport.

The effect of the hallucinogenic drug harmaline was tested on rat kidney proximal tubular solute and water transport, using in vivo micropuncture and electrophysiological techniques as well as in vitro biochemical techniques. During peritubular application harmaline (5 mmol/l) was found to block net tubular volume absorption reversibly (by 85%) through inhibition of active Na+ transport and possibly active HCO-3 transport. The inhibition was accompanied by a rapid strong depolarization of the tubular cell membranes. As a biochemical equivalent harmaline inhibited the Na+-K+-ATPase and the Mg2+-ATPase of peritubular cell membrane fractions as well as the HCO-3-stimulated ATPase of a brush border membrane fraction with similar kinetics. By studying glucose tracer efflux and by measuring cell membrane potential and conductance changes in response to glucose perfusions, no evidence for a direct effect of harmaline on Na+-glucose (or amino acid) cotransport mechanisms in the brush border could be obtained. The data suggest that harmaline does not specifically compete with Na+ for transport sites. Neither are the cotransport systems in the brush border membrane specifically inhibited, nor could the inhibition of the Na+ pump in the peritubular cell membrane simply result from a competition between harmaline and Na+.

Adenosine Triphosphatases↗