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Biomedical subjects

T W Schultz

Publications and source records attributed to T W Schultz.

At least 91 records · Page 5Linked to original sources
PubMed1991

QSARs for monosubstituted anilines eliciting the polar narcosis mechanism of action.

The relative toxicities (log IGC50(-1] of a fairly heterogeneous series of 66 anilines that were monosubstituted in the 2-, 3-, and 4-positions have been evaluated in the 48 h static Tetrahymena population growth impairment system. Quantitative structure-activity relationships (QSARs) were examined using the 1-octanol/water partition coefficient (log KOW) and the summation of the Hammett sigma electronic substituent constant (sigma sigma) as orthogonal independent predictors. Four chemicals, 4-decylaniline, 4-dodecylaniline, 4-tritylaniline and 4-aminophenethyl alcohol, did not elicit the measured response at saturation. Five chemicals, 2-aminophenol, 2-phenylenediamine, 4-aminophenol, 4-phenylenediamine and 4-nitroaniline, had an altered HPLC spectrum with time. As previously reported, the parent compound, aniline, as well as the 4-position halogen derivatives have been shown to be aberrantly more toxic than expected. None of these chemicals were included in QSAR development which employed linear regression analysis. Log IGC50(-1) = 0.599(log KOW) - 0.905 (n = 52, r2 = 0.885, s = 0.265, f = 383.65, Pr greater than f = 0.0001) was found to be a good predictor of relative toxicity of these monosubstituted anilines. The addition of sigma sigma as a second predictor did not improve the predictability of this QSAR. Abiotic loss over the duration of the assay varied markedly with derivative; however, chemical persistence was not considered to be a factor with this model. The above equation was strikingly similar to log IGC50(-1) = 0.595(log KOW) - 0.996 (n = 67, r2 = 0.866, s = 0.254, f = 421.64, Pr greater than f = 0.0001), a previously developed QSAR from data on a heterogeneous set of monosubstituted phenols. The data for these two equations were combined and subsequent regression analysis resulted in log IGC50(-1) = 0.588(log KOW) - 0.939 (n = 119, r2 = 0.873, s = 0.261, f = 806.49, Pr greater than f = 0.0001). The authors feel that this represents the log KOW-dependent QSAR in the Tetrahymena population growth assay for the polar narcosis mechanism of toxic action.

Aniline Compounds↗
PubMed1991

QSARs for selected aliphatic and aromatic amines.

The relative toxicity of 24 selected amines was evaluated in the 48 h Tetrahymena pyriformis static population growth impairment assay and compared with literature data for the 96 h Pimephales promelas flow-through mortality assay. Chemicals selected included normal and branched aliphatic primary amines, 4-position alkyl-substituted primary aromatic amines, as well as secondary and tertiary amines. Three amines were not toxic at saturation in the Tetrahymena system, whereas one amine was not toxic at saturation in the Pimephales system. Due to the aberrantly high toxicity of aniline observed in the Tetrahymena system, this chemical was not included in the analyses. For QSAR development, toxicity measured as log IGC50(-1) and log LC50(-1), respectively, was regressed against the log of the 1-octanol/water partition coefficient (log KOW). Both toxicity and hydrophobicity varied over five orders of magnitude. The model, log IGC50(-1) = 0.72(log KOW) - 1.64 (n = 20, r2 = 0.92) (1), was found to be a good predictor of toxicity in the Tetrahymena system. Similarly, the model, log LC50(-1) = 0.80(log KOW) - 1.80 (n = 23, r2 = 0.96) (2), was found to be a good predictor of toxicity in the Pimephales system. A comparison of Eqns (1) and (2) showed the models to be very similar. Therefore, as seen by the model, log LC50(-1) = 1.11(log IGC50(-1] - 0.01 (n = 20, r2 = 0.93) (3), a regression of the log toxicities gave a slope of one, an intercept of zero and a high correlation.

Amines↗
PubMed1991

Fine structural aspects of postnatal development of feline lung.

Lung development was studied in late prenatal, 1-, 7-, 14-, and 21-days postnatal and adult cats. Cats were born with a few alveoli, and the lungs appeared to have patches of primitive air spaces (saccules). The saccules of prenatal kittens were thick walled, very cellular, and lined by type II pneumocytes. Eosinophils were observed in the septum, intraepithelially, and in the alveolar space of growing cats. Secondary septa were flanked by a double capillary network and divided saccules into multiple shallow alveoli. Septation was irregular and time dependent and not completed by day 231 of postnatal life. Elastic fibers accumulated at the tip of the septa, seemingly playing an important role in alveolar formation. Type II pneumocytes were located at the base of the secondary septa in growing cats, thus strengthening secondary septa to withstand the stresses of respiration. Pores of Kohn were not observed in growing cats.

Animals↗
PubMed1990

Structure-activity relationships for osteolathyrism. III. Substituted thiosemicarbazides.

Eight substituted thiosemicarbazides were assayed for their toxicity and teratogenicity using early embryos of Xenopus laevis. Results of the 96-h static tests on seven 4-position alkyl substituents were used for quantitative structure-activity relationship (QSAR) analyses, with thiosemicarbazide as the parent compound. The compounds induced malformations via the connective tissue defect osteolathyrism. Teratogenicity (log EC50) was negatively correlated with molar refractivity, suggesting that steric inhibitions were important in explaining the variations in biological activity due to changes in the 4-position substituent. It appeared that there were two separate modes of lethal action, one associated with the ring-containing substituents and the other with straight-chain substituents. However, QSARs were not developed for embryolethality (log LC50) or for the mortality/malformation index (LC50/EC50) due to the limited number of chemicals eliciting each lethal mode of action.

Animals↗
PubMed1990

Relationships of quantitative structure-activity for normal aliphatic alcohols.

The relative toxicity of 14 normal aliphatic alcohols has been determined as 48-hr 50% population growth inhibition (log BR, biological response) of Tetrahymena pyriformis. A linear relationship was observed between log BR and the 1-octanol/water partition coefficient (log Kow). Comparison of log BR with 96-hr 50% mortality data for Pimephales promelas revealed excellent agreement between the two test systems. A relatively constant steady-state biophase toxicant concentration is calculated for each alcohol. Calculated chemical activity increased with an increase in hydrocarbon chain length. In addition, there was good agreement between chemical activity and the activity coefficient for narcosis.

Alcohols↗
PubMed1988

Structure-activity relationships for osteolathyrism: II. Effects of alkyl-substituted acid hydrazides.

A series of 8 alkyl-substituted acid hydrazides were assayed for their toxicity and teratogenicity using early embryos of the frog Xenopus laevis. Each acid hydrazide was able to induce the connective tissue defect osteolathyrism. The 96-h toxicity (log LC50) and 96-h teratogenicity (log EC50) endpoints are correlated with hydrophobicity measured by the fragment substitution constant (Fr). These relationships suggest the rate limiting step is the ability of the chemical to reach the site of action. However, the teratogenic index (LC50/EC50) is negatively correlated with molar refractivity (MR), a substituent corrected molar volume term. This latter relationship suggests steric hindrance.

Animals↗
PubMed1988

Structure-toxicity relationships for selected benzyl alcohols and the polar narcosis mechanism of toxicity.

The relative toxicity of 20 ortho-, meta-, and para-position monoalkylated or monohalogenated benzyl alcohols has been determined as 50% population growth inhibition (log BR; biological response) to Tetrahymena pyriformis. Linear relationships are observed between log BR and the 1-octanol/water partition coefficient (log Kow) for both the alkylated and the halogenated series. Regression analysis of the combined data results in poor correlation with the model, log BR = 0.7085(log Kow) - 1.3018; n = 20, r2 = 0.644, s = 0.323. However, the predictability of this quantitative structure-activity relationship (QSAR) is sharply enhanced by the addition of the Hammett sigma constant (sigma) as a second molecular descriptor, log BR = 0.8395(log Kow) + 1.4322 (sigma) - 1.6823; n = 20, r2 = 0.923, s = 0.154. This latter QSAR uses the para-position sigma as an estimator of ortho-position effects and compares well with previous work with alkyl- or halogen-substituted phenols. It is thought to model the polar narcosis mode of toxic action.

Animals↗
PubMed1988

Pulmonary lesions induced by Pasteurella haemolytica in neutrophil sufficient and neutrophil deficient calves.

The role of neutrophils in the development of peracute lung lesions of bovine pneumonic pasteurellosis was investigated. Eight calves were divided into two groups of four calves each. Group I was treated with intravenous phosphate-buffered saline and served as the neutrophil sufficient calves. Group II was treated with intravenous hydroxyurea which produced a state of neutropenia. When peripheral blood neutrophil numbers dropped below 300 cells/microL in group II, all calves were challenged with an intrabronchial bolus of Pasteurella haemolytica in the log phase of growth. An acute inflammatory process occurred in both groups of calves indicated by a rise in body temperature. While pulmonary lesions occurred in both groups by six hours postinoculation, they varied in pathological characteristics. Pulmonary lesions in the neutrophil sufficient calves consisted of fibrinopurulent alveolitis-bronchiolitis with associated alveolar septal necrosis, interlobular edema, and intravascular thrombi. The neutrophil deficient calves had extensive intra-alveolar edema, interlobular edema, intraalveolar hemorrhage, atelectasis, and focal areas of alveolar septal necrosis. These results show that P. haemolytica can induce severe pulmonary tissue damage through both neutrophil dependent and neutrophil independent mechanisms.

Agranulocytosis↗
PubMed1987

Structure-activity relationships of selected pyridines. III. Log Kow analysis.

Twenty 2- and 3-position derivatives of pyridine (C5H5N) were tested following a short-term static protocol. Biological activity was monitored as population growth of Tetrahymena pyriformis. These data were combined with previously reported data for twenty 4-position derivatives. Structure-activity relationships were examined using Kow as the physicochemical descriptor. These data form three linear models: one for the non-H-polar derivatives and two for the H-polar derivatives. The latter two models are parallel but have no obvious basis for a priori selectivity. HPLC analysis for toxicant persistence shows that only the smaller non-H-polar derivatives have any significant abiotic loss over the duration of the biological testing.

Animals↗
PubMed1987

The use of the ionization constant (pKa) in selecting models of toxicity in phenols.

Phenols elicit a toxic response by one of two mechanisms: polar narcosis or uncoupling of oxidative phosphorylation, and pKa values appear to be useful in predicting the mechanism of toxic action of a given phenol. The relative biological response (log BR) of 21 selected phenols in the static Tetrahymena pyriformis population growth test was determined. Seven derivatives, including dinitro- and polyhalogen-substituted phenols, were selected for testing because they were potential uncoupling agents. The other 14 derivatives were all suspected polar narcotics. 1-octanol/water partition coefficient (log Kow)-dependent regression analysis of the two subsets of derivatives results in two linear equations. The polar narcosis model is log BR = 0.6128 (log Kow) - 1.1297; r2 = 0.958, s = 0.187. The uncoupling of oxidative phosphorylation model is log BR = 0.4485 (log Kow) + 0.3007; r2 = 0.985, s = 0.209. Polar narcotic chemicals have pKa values greater than 8.00, while uncoupling agents have pKa values less than 6.50. Combining descriptors and modeling across mechanisms of toxicity in the model log BR = 0.5671 (log Kow) - 0.1885 pKa + 0.8190; r2 = 0.958, s = 0.225.

Animals↗
PubMed1987

Structure-activity relationships for mono alkylated or halogenated phenols.

The quantitative structure-activity relationships between toxicity (log BR), monitored as cell population growth, and two molecular descriptors, the log 1-octanol/water partition coefficient (log Kow) and the Hammett sigma constant (sigma) or the ionization parameter (pKa) for a series of 17 ortho-, meta- and para-substituted alkylated or halogenated phenols have been examined. The equation: log BR = 0.7998 (log Kow) + 1.2447 (sigma) - 1.5538; r2 = 0.897 s = 0.170 has been found to be an excellent planar model for these chemicals. This model uses the para-position sigma constant as the estimator of ortho-position electronic effects. A similar equation: log BR = 0.7845 (log Kow) - 0.3702 (pKa) + 2.1144; r2 = 0.860 s = 0.199 has been developed using pKa in place of sigma.

Chlorophenols↗
PubMed1986

A relationship between diffusional transport in lipid membranes and a lipophilic-eutectic parameter.

A theoretical model has been developed to relate passive diffusional transport with a parameter termed the lipophilic-eutectic coefficient, Le. Based on this parameter it is proposed that the lipophilicity of a substance can be estimated. The method is based on the melting point lowering of a pure substance in the presence of an impurity of similar structure. Cholesterol was chosen as a model biological lipid because it is a neutral lipid that is found in relatively high concentrations in a variety of membranes. Transdermal absorption in humans and intestinal absorption in the rat both show a high degree of correlation with respect to Le. For our studies, Le appears to be as satisfactory as the partition coefficient for estimating lipophilicity and its determination is less demanding analytically.

Animals↗
PubMed1986

Relationships of quantitative structure-activity to comparative toxicity of selected phenols in the Pimephales promelas and Tetrahymena pyriformis test systems.

The relative toxic response of 27 selected phenols in the 96-hr acute flowthrough Pimephales promelas (fathead minnow) and the 48- to 60-hr chronic static Tetrahymena pyriformis (ciliate protozoan) test systems was evaluated. Log Kow-dependent linear regression analyses revealed that the data from each test system consisted of two linear equations. The less toxic chemicals form a relationship which models polar narcosis; these chemicals are slightly more active than the baseline toxicity of nonionic narcotic chemicals. The more toxic chemicals form a relationship which models uncoupling of oxidative phosphorylation. Regression analysis of fathead minnow toxicity (log LC50 (mol/liter] vs Tetrahymena toxicity (log BR (mmol/liter] showed good correlation between the two systems. An exception appears to be 4-nitrophenol, which is more active in the Tetrahymena system than in the fathead minnow and lies outside the 95% confidence interval. Reanalysis following deletion of 4-nitrophenol results in the equation log LC50 = -0.9192 (log BR) -3.5035; n = 26, r2 = 0.887.

Animals↗
PubMed1986

The changing economy and the family.

This study is concerned with the impact of changes in economic conditions on the family. "Three issues are considered in this paper. First, the reasons why the family is not fading away as an economic entity are discussed. The argument of this paper is that, despite the declines in various economic functions of the family and the increases in divorces and in other failures, the survival capacity of the family is both strong and robust." Second, the author contends that the economic approach should be extended to deal with the effects of the life-span revolution, shifts in prices and incomes, and the ability of the family to cope with these changes. Third, the hypothesis is put forward that intergenerational transfers are less important than increases over time in real per capita incomes and changes in income composition, its permanent and temporary components, and the sources of income. The geographical focus is worldwide.

Costs and Cost Analysis↗