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Biomedical subjects

H Rosenkranz

Publications and source records attributed to H Rosenkranz.

At least 19 recordsLinked to original sources
PubMed2001

In wounded sugar beet (Beta vulgaris L.) tap-root, hexose accumulation correlates with the induction of a vacuolar invertase isoform.

Wounding of sugar beet tap-root causes an induction of invertase activity, which contributes to post-harvest sucrose losses. In this first comprehensive monitoring of wound-induced invertase mRNAs, proteins, enzyme activities, and tissue hexose concentrations, the VI isoform responsible for wound-induced hexose accumulation in mature tap-root could be identified.

Adaptation, Physiological↗
PubMed1991

Use of artificial intelligence in structure-affinity correlations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) receptor ligands.

The Computer-Automated Structure Evaluation (CASE) Program, an expert system that automatically selects relevant descriptors for structure-activity relationships, has been used to analyze the binding of various ligands to the tetrachloro-dibenzo-p-dioxin (TCDD) receptor or Ah receptor. Two databases were analyzed. One database contained 136 polycyclic aromatic hydrocarbons (PAH), substituted dibenzo-p-dioxins, dibenzofurans and biphenyls whose binding affinities were measured by a sucrose density gradient technique. The other 87 compound database contained PAH, nitro-PAH, halo-PAH and N-heterocycles. Their binding affinities were measured by the electrofocusing assay. Within each training set significant correlations between the affinity for the TCDD receptor and relevant molecular fragments identified by the CASE program were observed. Among the halogenated aromatic hydrocarbons, fragments containing lateral halogens and a longitudinal hydrogen appeared important for TCDD receptor binding. The fragments of PAH and heterocyclic compounds that were most activating with respect to TCDD receptor binding were found to contain the classical 'bay' region and were in fact identical to the fragments found previously to be related to carcinogenicity. It was found that the activating fragments from PAH and heterocyclic compounds were different from those found within the halogenated compounds such as dibenzo-p-dioxins, dibenzofurans and biphenyls. One interpretation of the data is that two different recognition sites may be involved in Ah receptor binding.

Artificial Intelligence↗
PubMed1991

Structure-activity relations: maximizing the usefulness of mutagenicity and carcinogenicity databases.

The most important criteria for the development and analysis of databases for elucidating the structural bases of toxicological activity include the integrity of the databases with respect to uniformity of the experimental protocol and interpretation of the test results and inclusion of chemicals representing different chemical classes and differing mechanisms of action. Within these criteria, it is demonstrated that when the chemicals are chosen at random, the larger the database, the better the predictivity of chemicals not included in the learning set. It is shown however, that when chemicals are selected on the basis of structural features, that a learning set of approximately 180 chemicals is as informative as a database consisting of 800 chemicals chosen at random.

Animals↗
PubMed1990

Quantitative factors in chemical carcinogenesis: variation in carcinogenic potency.

The quantitative assessment of toxicological data on the carcinogenic potential of chemicals requires consideration of a number of factors, including mathematical models of the mechanism of carcinogenic action and pharmacokinetic models for the metabolic activation of the parent compound to its reactive metabolite. In this article, the use of such models in estimating carcinogenic potency and in predicting risks at low levels of exposure is discussed, along with other factors involved in the evaluation of carcinogen bioassay data. The Carcinogenic Potency Database (CPDB) established by Gold et al. (1984, Environ. Health Perspect. 58, 9-322) is used to illustrate the application of quantitative approaches to carcinogenic risk assessment and to examine the variation in the potency of chemical carcinogens. Based on an analysis of 585 experiments selected from the CPDB, the risk-specific (10(-6) doses (RSDs) obtained by linear extrapolation from the TD50 were generally within a factor of 5-10 of those derived from the linearized multistage model. The RSDs obtained by linear extrapolation from the TD50 are roughly log-normally distributed with a median of about 20-90 ng/kg/day, depending on the subset of the CPDB considered. This distribution has been used by Rulis (1986, in Food Protection Technology (C. W. Felix, Ed.), pp. 29-37, Lewis, Chelsea, MI) to explore the concept of a threshold of regulation for chemical carcinogens present in the environment at low levels.

Animals↗
PubMed1987

Biochemical studies on the catalysis of nitrosation by bacteria.

Biochemical and microbiological studies were conducted to characterize the mechanism of bacterial formation of N-nitrosomorpholine from morpholine and nitrite at neutral pH. Nitrosating activity was markedly induced when bacteria were cultured anaerobically in minimal culture medium containing nitrate, while the presence of cysteine or tungsten in the medium inhibited induction. Of various metals, coenzymes and inhibitors tested for their effects on in vitro nitrosation of morpholine, potassium cyanide, sodium azide, NAD(P)H and nitrate strongly inhibited nitrosation. Several mutants of Escherichia coli A10 strain were prepared in order to examine whether nitrosation activity is linked to specific loci. Niridazole-resistant mutants, which lack nitroreductase, had as much nitrosating activity as the original E. coli A10, but chlorate-resistant mutants had completely lost this activity. A good correlation was observed between nitrate reductase activity and nitrosating activity in these mutants. These results indicate that bacterial nitrosation is an enzyme-mediated reaction closely associated with molybdenoenzymes such as the nitrate reductase/formate hydrogenlyase system.

Azides↗
PubMed1986

Contribution of organic particulates to respiratory cancer.

This paper presents some of the issues that remain to be resolved in order to assess the risk of cancer related to exposure to organic particulates. Most reviews of the effects of organic particulates from the outdoor environment on the risk of lung cancer show that this source seems to play a minor role. However, as fuel use and chemical composition of air pollutants change, the contribution of outdoor pollution as a cause of cancer may also change. Indoor air pollution is a more important source of exposure to organic particulates than is outdoor exposure. Although there is clear evidence that in occupational settings organic particulates cause human cancer, there has been almost no study of exposure to these types of particulates within indoor settings. Previous research has focused on cigarette smoke as the major indoor pollutant, but more specific characterization of contaminants in both the workplace and the home is required. The health effects of the higher levels of some of these contaminants in the workplace should be evaluated and the results extrapolated to populations exposed to lower levels in the home. Extensive research is needed to characterize organic particulate mixtures appropriately and test them for carcinogenicity. Studies on the health risks of nitropolynuclear aromatic hydrocarbons and polychlorinated dibenzodioxins and dibenzofurans are reviewed, but their contribution to the overall burden of respiratory cancer in humans cannot be estimated at this time. Characterization of mixtures, assessment of exposures, and linkage of exposures to health effects are the objectives of the recommendations proposed for further research.

Air Pollutants↗
PubMed1979

Comparative study of the binding of acylureidopenicillins and carbenicillin to human serum proteins.

The binding of the acylureidopenicillins azlocillin and mezlocillin to serum proteins was investigated by means of equilibrium dialysis and ultracentrifugation. The penicillin concentrations were determined by the agar diffusion test and by circular dichroism. The degree of binding is dependent on the penicillin concentration. At a mean penicillin concentration of 20 microgram/ml 39% of azlocillin is bound by serum proteins and 35% of mezlocillin. The acylureidopenicillins are bound to about the same degree by the two proteins albumin and gamma globulin, which occur in different concentrations in serum. The binding affinity delta F degree for the interaction between azlocillin and mezlocillin to human albumin is equal to -15,389 J/mol. The corresponding values for the binding of ampicillin and carbenicillin are -17,340 and -16,800 J/mol. Albumin has one binding site of a high affinity and two binding sites of a low affinity for the acylureidopenicillins. Measurements of partition coefficients of the penicillins for isobutanol and aqueous solution show that the interaction between acylureidopenicillins and serum is mainly hydrophobic in nature. This can be deduced from the fact that for example in the presence of sisomicin azlocillin is not displaced from its albumin binding site, in contrast to carbenicillin. The reason for this difference in behaviour lies in the fact that carbenicillin, like sisomicin, is bound to the serum proteins mainly by ionic bonds. In the case of azlocillin, however, hydrophobic bounds predominate which are not influenced by the ionic bonds of sisomicin.

Blood Proteins↗
PubMed1978

Binding of sisomicin and streptomycin to human albumin.

The aminoglycosides of the kanamycin and neomycin series are displaced from their protein binding by very low Ca++ ion concentrations, whereas streptomycin is displaced only by very high Ca++ ion concentrations. For streptomycin, therefore, the binding mechanism must differ from that for the other aminoglycosides. The displacing reaction cannot be described by the law of mass action, combining the binding equations. Several possible reasons, such as complex formation and changes in the conformation of albumin, are discussed. Complex formation between sisomicin and the lanthanide ion Nd+++, which has the same ionic radius as the Ca++ ion, could be excluded by recording the difference absorption spectrum. The displacement of the aminoglycosides from their protein binding by Ca++ ions (as well as the pH dependence of the protein binding) suggests that ionic bonds are involved in the interactions between aminoglycosides and serum proteins.

Calcium↗
PubMed1978

Binding of aminoglycoside antibiotics to human serum proteins. III. Effect of experimental conditions.

The binding of several aminoglycoside antibiotics to human serum proteins was studied under varying experimental conditions. The protein binding was determined by means of equilibrium dialysis and, with sisomicin and gentamicin, also by the ultracentrifuge method in the presence and in the absence of Ca++ and Mg++ ions. The technical experimental procedure (dialysis, ultrafiltration, ultracentrifugation) has no effect on protein binding contrary to the physico-chemical conditions (varying concentrations of Ca++ and Mg++ ions). Under experimental conditions closely conforming to physiological conditions, the aminoglycosides of the kanamycin and neomycin series are not bound by the serum proteins, independent of the assay method used, whereas streptomycin is bound under these conditions. In the absence of divalent cations all the aminoglycosides studied were bound by the serum proteins to varying degrees; the fewer the OH groups contained in the aminoglycoside molecule the greater the rate of protein binding. At equal protein concentration, the albumin fraction of the serum has as great a binding capacity for sisomicin as gamma globulin. Alpha-1 and beta-1 globulin, however, are unable to bind sisomicin.

Aminoglycosides↗
PubMed1978

Ionic binding of aminoglycosides to human serum albumin in the absence of divalent cations. IV. Effect of structure, ph and concentration.

The binding of sisomicin and streptomycin to human serum albumin was studied in the absence of divalent cations by means of the dialysis method. Hydrophobic bonds between albumin and sisomicin or streptomycin can be excluded by nuclear magnetic resonance measurements. The presence of hydrogen bonds is made unlikely according to the result that the binding of the aminoglycosides decreases with increasing number of OH groups in the aminoglycoside molecule. The pH dependence of protein binding suggests that ionic bonds are involved in the binding of aminoglycosides. On the basis of the concentration dependence of the albumin binding of sisomicin and streptomycin we determined the binding affinities delta F degrees, the binding constants K1, and the maximum number n of aminoglycoside molecules that can be bound by a molecule of albumin in the absence of Ca++ ions. The results were as follows: Sisomicin: delta F degrees = -4189 cal/mole, K1 = 900 1/mole, n = 12; Streptomycin: delta F degrees = 3512 cal/mole, K1 = 300 1/mole, n = 17.

Cations, Divalent↗
PubMed1976

[Binding of sisomicin and gentamicin to serum proteins (author's transl)].

The binding of sisomicin and gentamicin to the proteins of human serum was investigated by the dialysis method at 37 degrees C. The antibiotic concentrations were determined by the disc diffusion assay as well as by measurements of the optical rotation of the antibiotics in the buffer solutions. Serum was dialyzed against buffer solutions to obtain the standards for the antibiotic assay with regard to the electrolytical exchange at dialysis. In studies on protein binding of sisomicin and gentamicin no measurable binding to human serum proteins could be found, neither in the therapeutically possible concentrations nor at higher ones. Therefore a different binding of the two antibiotics cannot be the reason of the advantage of sisomicin over gentamicin in tests in vivo with animals described in literature nor of its higher activity against several bacterial strains of different species tested in the presence of serum.

Anti-Bacterial Agents↗