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W Estelberger

Publications and source records attributed to W Estelberger.

At least 19 recordsLinked to original sources
PubMed1997

Information theoretical concepts in clinical chemistry: the use of spreadsheet programs for convenient calculation of information theoretical quantities.

Information theoretical concepts can be used as most valuable tools for evaluating clinical chemical tests. They offer several advantages over the conventional test evaluation by Bayesian concepts. Although long known, information theory has failed to gain widespread acceptance among clinical chemists, probably due to the rather laborious computation of the necessary quantities. To resolve this technical problem, this paper demonstrates how commonly available computer spreadsheet programs can assist in the computation of information theoretical quantities such as the diverse entropies and the information content. Two spreadsheet versions are presented: firstly, a working sheet is developed for information theoretical evaluation of a two-by-two contingency table corresponding to a dichotomous diagnostic problem (e.g., diseased versus non-diseased) and a dichotomous diagnostic test outcome (e.g., normal versus abnormal), and secondly, a working sheet is shown for a more general situation with up to ten diagnostic alternatives and up to ten possible test outcomes. Typical examples for application of these tools are demonstrated.

Chemistry, Clinical↗
PubMed1997

Selective decrease of serum immunoglobulin G1 as a marker of malignant transformation in colorectal tissue.

BACKGROUND: Malignant diseases of various origins were previously shown to be associated with a characteristic and highly significant change in the serum pattern of immunoglobulin (Ig)G subclasses, comprised of a decrease in %IgG1 and an increase in %IgG2 relative to and independent of the absolute concentration of total IgG. The goal of the current study was to evaluate this phenomenon as an indirect marker in the primary diagnosis of colorectal carcinoma. METHODS: Using affinity chromatography, IgG1, IgG2, and total IgG were determined in 36 patients with colorectal carcinoma of different stages and compared with 162 apparently healthy controls. RESULTS: It was found that: 1) the mean values for %IgG1 and %IgG2 of all carcinoma patients differed significantly from those of the controls; 2) no quantitative association was found with tumor stages, and four of five patients with incipient adenocarcinoma within a polyp exhibited the characteristic shift in IgG subclasses; 3) based on a calculated cutoff, the specificity and sensitivity of %IgG1 to discriminate between controls and carcinoma patients was found to be 88% and 74%, respectively; and 4) a quantitative correlation between individual %IgG1 values and the probability of correct assignment to carcinoma patients or controls was established. CONCLUSIONS: The significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG represents an indirect, tissue nonspecific, and early marker of malignant proliferation that distinguishes colorectal carcinoma patients from healthy controls with a specificity of 88% and sensitivity of 74%.

Adenocarcinoma↗
PubMed1996

Selective decrease in serum immunoglobulin G1. A tissue nonspecific tumor marker detecting early stages of gynecologic malignant disease with high efficiency.

BACKGROUND: Malignant diseases of various tissue origin have previously been found to be associated with a characteristic shift in the serum pattern of IgG subclasses, i.e., a highly significant reduction of the percent of IgG1 and an increase of the percentage of IgG2 relative to the total IgG. In the present study we examined the diagnostic performance of this indirect tumor marker in patients with carcinomas of various sites within the female reproductive tract. METHODS: Using quantitative affinity chromatography, the percents of IgG1 and IgG2 in the total IgG were determined for 207 patients with carcinoma of the ovary, cervix, or corpus uteri, prior to any treatment. The data were compared with those of 135 age matched healthy females and 52 patients with benign gynecologic diseases. RESULTS: It was found that (1) mean values for the percents of IgG1 and IgG2 of all of the cancer patients differed significantly from those of the patients with benign disease and healthy controls; (2) no differences were noted between carcinomas of the ovary, corpus or cervix uteri; (3) early stages of carcinoma exhibited the effect to the same extent as late stages; (4) the specificity of the percent of IgG1 to discriminate between controls and cancer patients ranged between 90 and 100%, regardless of localization and stage of tumor; and (5) whereas with ovarian cancer CA 125 showed a slightly greater sensitivity, the percent of IgG1 was by far more sensitive than the conventional markers CA 125, TPA, CEA, Ferritin, and SCC to diagnose carcinoma of the cervix and corpus uteri, notably at early stages. Combined analysis of the percent of IgG1 and CA 125 and/or TPA led to an increase in sensitivity with tumors of all three sites. CONCLUSIONS: Thus, the determination of the percent of IgG1 by itself and/or in combination with conventional markers may provide relevant information regarding the noninvasive detection of early stages of gynecologic carcinoma.

Adult↗
PubMed1996

Neural networks as a tool for compact representation of ab initio molecular potential energy surfaces.

Ab initio quantum chemical calculations of molecular properties such as, e.g., torsional potential energies, require massive computational effort even for moderately sized molecules, if basis sets with a reasonable quality are employed. Using ab initio data on conformational properties of the cofactor (6R,1'R,2'S)-5,6,7,8-tetrahydrobiopterin, we demonstrate that error backpropagation networks can be established that efficiently approximate complicated functional relationships such as torsional potential energy surfaces of a flexible molecule. Our pilot simulations suggest that properly trained neural networks might provide an extremely compact storage medium for quantum chemically obtained information. Moreover, they are outstandingly comfortable tools when it comes to making use of the stored information. One possible application is demonstrated, namely, computation of relaxed torsional energy surfaces.

Biopterins↗
PubMed1996

IgG1--as the only subclass of human serum IgG--spontaneously undergoes O2(-)-induced, noncovalent self-aggregation upon storage at room temperature.

An apparent gradual decrease of IgG1 serum levels of up to 40% occurs within 48 h of storage at room temperature. The effect does not concern any other IgG subclass, and is more pronounced in sera of smokers. A linear correlation was found between the extent of this "storage effect" and the initial concentration of IgG1, which rules out an enzymatic process following Michaelis-Menten kinetics. PAGE and Western blots of density gradient separated serum proteins revealed the presence of noncovalent self aggregates of IgG1 in stored sera. Addition of superoxide dismutase prevented both the formation of aggregates as well as the decay of IgG1 values. It is concluded that the instability of IgG1 is due to an enhanced propensity of this molecule to form self-aggregates, whereby O2(-)-radicals play a functional role. This mechanism, however, is not relevant to a previously detected selective decrease of relative IgG1 levels in sera of patients afflicted with malignant diseases of various tissue origin.

Blood Specimen Collection↗
PubMed1996

Effects of pteridines on chloramine-T-induced growth inhibition in E. coli strains: correlations with molecular structure.

Little is known about the biological significance of most pteridines, despite their ubiquitous occurrence in living cells. Seventeen different pteridines were tested for their ability to modulate the growth inhibitory effect of the disinfectant chloramine-T on three different strains of Escherichia coli bacteria. We found striking differences between the pteridine derivatives: whereas aromatic pterins with a hydroxy function at side chain atom C2' increased the growth inhibition, those with a 7,8-dihydro structure exerted a suppressive effect. These results are in excellent agreement with previously observed effects of pteridine derivatives on chloramine-T-induced luminol-dependent chemiluminescence, and together, are highly suggestive of a general interaction of these compounds with oxygen or chlorine free radicals. This interaction is likely to have biological significance and might offer an explanation for the widespread occurrence of pteridines.

Anti-Infective Agents, Local↗
PubMed1995

Conformational investigation of the cofactor (6R,1'R,2'S-)-5,6,7,8-tetrahydrobiopterin.

(6R,1'R,2'S)-5,6,7,8-Tetrahydrobiopterin is an essential cofactor for several enzymes. Different theoretical models (molecular mechanics, semiempirical quantum chemical calculations) investigating its stereostructure have yielded diverging answers. To clarify these issues, combined molecular mechanical and ab initio quantum chemical calculations were performed, investigating both the axial and the equatorial orientation of the dihydroxypropyl side-chain. After geometry optimization, the resulting most stable structures were subjected to systematic variation of two side-chain torsional angles in order to study the conformational flexibility. The axial side-chain orientation is slightly more stable than the equatorial form. Two weak intramolecular hydrogen bonds contribute to stabilization of the axial conformer, while in the equatorial conformer only one hydrogen bond is detected. An 8 ps molecular dynamical simulation at 310 K suggests that, at realistic temperatures, the molecule is flexible enough to undergo internal motions (rotations, vibrations), rendering questionable the biological significance of mere conformational properties.

Biopterins↗
PubMed1995

The conformational flexibility of 5,6,7,8-tetrahydrobiopterin and 5,6,7,8-tetrahydroneopterin: a molecular dynamical simulation.

5,6,7,8-Tetrahydrobiopterin is an essential cofactor of diverse enzymes. Of the eight possible stereoisomers, only the 6R,1'R,2'S-configuration is biologically active. Other stereoisomers, as well as other reduced pterins such as, e.g. 5,6,7,8-tetrahydroneopterin, fail to exhibit significant cofactor activity. Different theoretical models (molecular mechanics, semi-empirical quantum chemical calculations) investigating the stereostructure of tetrahydrobiopterin have yielded diverging answers. It has been claimed on the basis of semi-empirical quantum chemical calculations that conformational properties, and thus particular features in overall shape, might be responsible for the unique biological properties of natural tetrahydrobiopterin in contrast, e.g. to 6R,1'S,2'R-5,6,7,8-tetrahydroneopterin. Molecular dynamical simulations of both molecules at realistic temperatures demonstrate, however, that they possess sufficient conformational flexibility as to render questionable any biological significance of mere conformational properties.

Biopterins↗
PubMed1995

System identification of the low-dose kinetics of p-aminohippuric acid.

The renal clearance of p-aminohippuric acid, due to tubular secretion in addition to glomerular filtration, can only be determined by kinetic experiments. Maximal information can be gained from observed temporal marker concentration profiles by fitting dynamic mathematical models of the processes involved, such as absorption, distribution, and elimination, to the kinetic data. Thereby the values of the system constants, such as fractional elimination or fractional distribution rates, and their accuracy measures are determined by methods which are based firstly on measured time-dependent data elicited in an individual test object by perturbing inputs and secondly, on mathematical formulations of prior knowledge of the underlying physiological system. Such methods of model adaptation are called system identification. In this context a computer-based method of system identification and error estimation for the system constants of two-compartment models matched a dynamic concentration profiles of p-aminohippuric acid is presented. The method is used of single-injection experiments to demonstrate that such a technique is able to correctly estimate the clearance of p-aminohippuric acid if sufficiently long experimental protocols are chosen, and to ascertain the sufficient length of a protocol for an individual subject. The renal clearance of p-aminohippuric acid is known to exhibit concentration-dependence generally, but to achieve its maximal value when low doses are applied. The present study deals with the low-dose kinetics of p-aminohippuric acid.

Adult↗
PubMed1995

Determination of the glomerular filtration rate by identification of sinistrin kinetics.

A computer-based method of system identification and estimation of parameter variance for two-compartment models matched to dynamic sinistrin concentration profiles for the determination of glomerular filtration rate is described. Thereby a procedure for the judgment of the optimal sampling time horizon is presented. Since single-injection techniques are suspected of yielding systematic overestimation of the glomerular filtration rate, a method is demonstrated confirming that such a technique employing sinistrin kinetics can be used to correctly determine the glomerular filtration rate. The validation of the system parameters gained by the single-injection method is made through prediction of the concentration contour under a constant infusion regimen in the same subject on a different occasion. This was performed in healthy controls and in patients with various degrees of renal insufficiency. Upon consideration of the dependence of the clearance estimates and their variances on the protocol duration in test subjects examined from four to ten hours, an adaptive design of the protocol length is developed.

Adult↗
PubMed1993

Determination of renal clearance of neopterin by a pharmacokinetic approach.

Pharmacokinetic modelling was used to determine the glomerular filtration rate and tubular secretion of neopterin, a marker for cellular immune activation. The method involves parameter identification employing the transient venous plasma concentration profiles of marker substances. By combined i.v. injection of neopterin and inulin which is excreted exclusively via glomerular filtration, neopterin was shown to be excreted in addition to glomerular filtration, by tubular secretion: clearance of inulin, 112 (S.D. 2.2) ml/liter; clearance of neopterin, 499 (S.D. 79.7) ml/min. A pilot experiment using in addition p-amino hippuric acid suggests that neopterin and p-amino hippuric acid may employ the same carrier system for tubular secretion.

Adult↗
PubMed1993

A decrease in reactive disulfide bonds of serum IgG signals a characteristic change in the IgG subclass patterns of rats bearing experimental tumors.

Previous studies have shown that human IgG1 contains a 'reactive' disulfide bridge (SS*), detectable by a 24-hour disulfide exchange reaction, and that the serum level of this IgG subclass is selectively diminished in patients with various malignant diseases. Here we present evidence that in rats IgG2b is the only subclass that carries one SS* per molecule. Furthermore, it is shown that rats inoculated with experimental tumor lines, i.e., the Yoshida hepatoma ascites tumor and the Walker 256 carcinosarcoma growing in ascites or as solid tumor, exhibit significantly decreased SS* per mole IgG which corresponds to a selective diminution of IgG2b. Although at later stages there is a quantitative correlation with the tumor burden, with the Walker tumor this effect becomes significant as early as 24 h after inoculation, i.e., well before exponential tumor growth and an absolute reduction of total IgG. Control animals injected intraperitoneally with either viable spleen cells or irradiated Walker 256 cells did not show comparable alterations in their IgG subclass profile. Thus, the selective defect of IgG2b requires the presence of viable and proliferating tumor cells. Possible mechanism(s) of tumor-associated shifts in IgG subclasses are discussed.

Animals↗
PubMed1991

Sigma S, a measure of reactive sulfur groups of immunoglobulin G, is a sensitive tumor marker discriminating different stages of breast cancer.

Sigma S is a measure of the disulfide bonds and free thiol groups of serum immunoglobulin (Ig) G, as determined by the reaction with dithionitrobenzoate. Significant decreases of sigma S previously were detected in malignant compared with benign diseases of various organs. This study shows the application of sigma S for the diagnosis of breast cancer. The following results were obtained. First, 132 patients with benign breast diseases showed a sigma S of 1.48 +/- 0.29 (standard deviation) per mole IgG; this was not different from 1.51 +/- 0.36 found in 182 controls. In contrast, IgG from 198 patients with primary breast carcinoma of all four stages (tumor-node-metastasis system) gave a sigma S of 1.22 +/- 0.29, a significant (P less than 0.0001) decrease of sigma S from benign to malignant breast disease. Second, sigma S values of single Stages I, II, III, and IV, were 1.27 (n = 59), 1.23 (n = 83), 1.19 (n = 35), and 1.10 (n = 21), respectively, each significantly different from sigma S in benign disease and showing a decreasing trend with increasing tumor progress. Differences were significant between Stages I and IV (P less than 0.025) and II and IV (P less than 0.05). Third, 63% of Stage I breast carcinoma patients had sigma S values below a critical threshold of 1.38. This serum positivity rose to 90% in Stage IV. These values exceeded those reported with other tumor markers. The overall power of sigma S to distinguish between benign and malignant breast disease had a specificity of 61% and a sensitivity of 78%. Early stages (I and II) of breast cancer could be distinguished from benign diseases with 64% specificity and 69% sensitivity. Advanced Stage IV could be discriminated from early Stages I and II with 55% specificity and 71% sensitivity. Thus, the analysis of sigma S may significantly contribute to the surveillance of patients with breast cancer.

Adult↗
PubMed1989

Labile disulfide bonds and free thiol groups in human IgG. V. Association of postoperative mean 'sigma S' course and tumor recurrence in ovarian cancer.

Sigma S comprises both free thiol groups and labile S-S-bonds of the total IgG that react with dithionitrobenzoate. Previous investigations have shown that this parameter was significantly decreased in malignant diseases of various organ systems as compared with benign disorders of the respective organs. The present study on patients with ovarian cancer investigated whether a significant correlation exists between the post-operative course of sigma S and the clinical evidence. For this purpose, on the basis of former results, a value of sigma S of 1.25 was determined as a criterion between malignant and benign ovarian diseases. For each investigated case, the post-operative temporal average of sigma S was calculated (sigma S) and a value of 1.25 was used as discriminating threshold. A four-fold table was set up containing the frequencies of tumor recurrences and tumor free cases with sigma S less or greater than 1.25. In a total of 40 patients of ovarian cancer an association between sigma S less than 1.25 and increased frequency of recurrences was confirmed, with a probability of error of 1%. The total predictive value of the sigma S level was about 70% and is herewith comparable to the leading tumor marker CA 125 in ovarian cancer.

Biomarkers, Tumor↗
PubMed1989

Relationship between generation and plasma concentration of anorganic phosphorus. In vivo studies on dialysis patients and in vitro studies on erythrocytes.

The plasma concentration of inorganic phosphorus (Pi) was determined before, during and after hemodialysis in 28 patients with chronic renal failure. Pi plasma concentration decreased rapidly when hemodialysis was started but did not fall below normal levels during continued dialysis. These changes of Pi concentration were fitted to a model of Pi kinetics in which Pi delivery to plasma is a nonlinear function of the extracellular Pi concentration. In separate in vitro studies, erythrocytes from six subjects with normal renal function and from 14 patients with chronic renal failure were incubated in homologous plasma with various amounts of Pi added. All other factors known to affect the Pi shift between intra- and extracellular fluid compartments (pH, calcium concentration) were kept constant. The relation between Pi concentration in plasma used for incubation and in red cells after 1h incubation suggested a mechanism in which a high plasma concentration results in movement of Pi into red cells where Pi is stored most probably in glucose esters. At low Pi plasma concentration Pi is delivered to plasma at a rate which cannot be explained solely by passive movement of intracellular Pi to plasma but requires additional generation from intracellular storage forms. The generation and delivery of Pi in patients and in their erythrocytes indicate a simple cell-mediated Pi homeostasis counter-acting abnormal fluctuations of plasma Pi.

Adolescent↗
PubMed1988

Quantitative characterization of diet effects on glucose tolerance in rabbits.

Normal, atherogenic and butter-enriched diets were given to three groups of rabbits during six months. The effects of the three forms of diet after six months were examined with the intravenous glucose tolerance test, which was evaluated by computer-aided model-fitting and parameter identification. Long-term effects are reflected in parameters such as pancreas sensitivity and the glucose utilization rate constant as a measure of peripheral insulin sensitivity. In these terms, the atherogenic diet caused a diminution of both pancreatic and peripheral sensitivity, whereas the butter-enriched diet led to an increase in glucose utilization and a decrease in pancreatic sensitivity relative to the system parameters of the normally fed control animals. Related to the findings about metabolic regulation are indications for an endocrinological approach to the problems of cholesterogenesis and atheroma formation.

Animals↗
PubMed1981

System identification of the control of gluconeogenesis in the intact organism under conditions of long-term stress.

In this article a system-theoretic approach to hormonal control of gluconeogenesis as observed in the intact organism under hypoglycemia and hypoxia is attempted. Under such conditions the secretion of the stress hormone corticosterone by the adrenal cortex is effected by neural control centres inducing the synthesis of gluconeogenetic enzymes which catalyze the production of glucose from amino acids originating from body tissues. The time courses of the hormonal, enzymatic and metabolic quantities measured are evaluated in the framework of a model in the form of a system of differential equations, the parameters of which are determined by a numerical search procedure.

Animals↗