QSAR's from similarity matrices. Technique validation and application in the comparison of different similarity evaluation methods.

It has recently been shown that good quantitative structure-activity relationships can be obtained through statistical analysis of molecular similarity matrices. Here we extend the technique to seven additional molecular series, previously studied using Comparative Molecular Field Analysis (CoMFA) methodology. The results are used to confirm technique applicability across a wider range of QSAR problems and to compare quantitatively the ability of various similarity indices to describe biological systems.

Long-Term Anaerobic Metabolism in Root Tissue (Metabolic Products of Pyruvate Metabolism).

The onset of anaerobiosis in barley root tissue (Hordeum vulgare L. cv Himalaya) results in the following metabolic responses. There are rapid increases in the levels of pyruvate, lactate, and ethanol.

Structure-activity relationships from molecular similarity matrices.

An alternative method for determining structure-activity correlations is presented. Ligand molecules are described using data matrices derived from the results of N by N (each molecule compared to every other) molecular similarity calculations. The matrices were analyzed using a neural network pattern recognition technique and partial least squares statistics, with the results obtained compared to those achieved using comparative molecular field analysis (CoMFA).

Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man.

Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglobulin antibody was also used to detect immunoglobulin deposits on pig tissues.

Similarity screening of molecular data sets.

Three-dimensional (3D)-database searches are now being widely applied to determine potential new active molecules. Many structural data sets obtained as a result of these searches are still large in size. In this paper we apply molecular similarity calculations as a rapid method to screen two such data sets.

The calculation of molecular similarity: alternative formulas, data manipulation and graphical display.

The use of electrostatic potential comparisons between molecules for the elucidation of structure activity relationships is now a well-established modeling technique. The Carbo and Hodgkin similarity indices are used extensively to make quantitative comparisons of this nature; yet their roots are found in the overlap of electron density distribution, with both formulas utilizing a product-based numerator. Two new similarity indices are suggested that calculate the electrostatic potential similarity using a difference-based numerator.

Purification and characterization of an anaerobically induced alanine aminotransferase from barley roots.

Alanine aminotransferase (AlaAT, EC 2.6.1.

Effects of an infusion of morphine into the accumbens nucleus upon acquisition of hypoalgesic and fear responses in rats exposed to a heart stressor.

Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned hypoalgesic (Experiment 1) and fear (Experiment 4) response. This impairment was dose-dependent (Experiment 2) and mediated by opioid receptors in the accumbens nucleus, because it was removed by a systemic (Experiment 3a) or by an accumbal (Experiment 3b) infusion of naloxone.

Identification and characterization of a hypoxically induced maize lactate dehydrogenase gene.

In cereal root tissue, hypoxia induces the enzyme lactate dehydrogenase (LDH); (S)-lactate:NADH oxidoreductase, EC 1.1.1.

Enzyme-linked immunosorbent assays for the measurement of blood group A and B glycosyltransferase activities.

ELISA assays have been developed for alpha(1-3)N-acetylgalactosaminyltransferase (blood group A transferase) and alpha(1-3)galactosyltransferase (blood group B transferase) activities. In these assays, microtitre plates coated with the bovine serum albumin conjugate of a synthetic Fuc alpha 1-2Gal beta-R acceptor substrate are incubated with the appropriate nucleotide donor (UDP-GalNAc or UDP-Gal) and human serum as the enzyme source. The resulting trisaccharide products Fuc alpha 1-2(GalNAc alpha 1-3)Gal beta-R-BSA or Fuc alpha 1-2(Gal alpha 1-3)Gal beta-R-BSA are detected and quantified with monoclonal antibodies selected not to cross-react with the substrate structure.

Serological and chemical specificities of twelve monoclonal anti-Lea and anti-Leb antibodies.

The serological specificities of twelve hybridomas were compared as to their chemical reactivity as determined using direct binding to synthetic carbohydrate structures. All anti-Lea cross-react with type-1-precursor structures and three different variants of anti-Lea could be defined by their binding to type-3-precursor chains, sialylated compounds and the monosaccharide D-galactose. Three major reactivity patterns were also identified among anti-Leb reagents.

Forestomach neoplasms in Fischer F344/N rats and B6C3F1 mice exposed to diglycidyl resorcinol ether--an epoxy resin.

Repeated dose (14 days), subchronic (13 wk) and chronic (2 yr) studies were carried out in succession to evaluate the toxic and carcinogenic effects of diglycidyl resorcinol ether (DGRE), a liquid spray epoxy resin, in F344/N rats and B6C3F1 mice. DGRE in corn oil was administered by gavage for 14 consecutive days in the repeated dose study and 5 days/wk in the subchronic and chronic studies. The mortality rate was increased in rats and mice in the repeated dose and subchronic studies.

An enzyme-linked immunosorbent assay for the measurement of Lewis blood-group alpha-(1----4)-fucosyltransferase activity.

An enzyme-linked immunosorbent assay (ELISA) has been developed for the Lewis blood-group associated alpha-(1----4)-fucosyltransferase activity. Microtiter plates coated with the bovine serum albumin conjugate of a synthetic beta-D-Galp-(1----3)-beta-D-GlcpNAc disaccharide are incubated with a fucosyltransferase preparation in the presence of guanosine 5'-diphosphofucose. The resulting immobilized Lewis-a active trisaccharide beta-D-Galp-(1----3)-[alpha-L-Fucp-(1----4)]-beta-D-GlcpNAc is then detected and quantitated using a monoclonal anti-Lewis-a antibody.

Anaerobic induction of alanine aminotransferase in barley root tissue.

Alanine aminotransferase, otherwise called glutamate-pyruvate aminotransferase (GPT), activity increases up to fourfold during several days of anaerobic induction in barley (Hordeum vulgare L.) roots, reaching a maximum activity of 13 international units per gram fresh weight. This increase in activity paralleled the increase in alcohol dehydrogenase activity in the same root tissue.

Induction of alcohol dehydrogenase and lactate dehydrogenase in hypoxically induced barley.

In barley (Hordeum vulgare L.), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH) are induced by anaerobiosis in both aleurone layers and roots. Under aerobic conditions, developing seeds of cv Himalaya accumulate ADH activity, which survives seed drying and rehydration.

Thermal insulation of young calves exposed to cold.

Tissue, external and whole animal insulation values were determined for 12 newborn male Holstein calves continuously housed for two weeks in hutches within environmental chambers in which temperature was maintained at a constant 17 degrees C (three calves) or cycled on a daily basis either between -20 degrees and -8 degrees C (three calves) or between -30 degrees and -18 degrees C (six calves). Three of the six calves at the coldest temperature were outfitted with an insulated coat. The insulated coat provided calves a 52% increase in total insulation.

Health and metabolic responses of young calves housed at -30 degrees C to -8 degrees C.

Newborn, male, Holstein calves, were continuously housed for three weeks in calf hutches at 17 degrees C or in a thermal environment which varied rhythmically on a daily basis either between -20 degrees C and -8 degrees C (experiment A) or between -30 degrees C and -18 degrees C (experiment B). Compared to warm-housed calves, cold-housed calves in experiment A had metabolic rates which were significantly higher (p less than 0.001) in a standing position but which were not significantly different (p less than 0.

Rapid spread of transposable p elements in experimental populations of Drosophila melanogaster.

The invasion of P elements in natural populations of Drosophila melanogaster was modeled by establishing laboratory populations with 1%, 5% and 10% P genomes and monitoring the populations for 20 generations. In one experiment, the ability of flies to either induce or suppress gonadal sterility in different generations was correlated with the amount of P element DNA. In a second experiment, the percentage of genomes that contained P elements, and the distribution of P elements among individual flies was monitored.

Mothers' and fathers' recognition of their newborns' photographs during the postpartum period.

In the present study, we have compared the ability of mothers and fathers to recognize their newborns' photographs during the early postpartum period. We suspected that fathers would prove to be less proficient than mothers, as a result of differences in the quality of their contact with their newborns. Our hypothesis was not confirmed.

Identification of glucose and nucleoside transport proteins in neonatal pig erythrocytes using monoclonal antibodies against band 4.5 polypeptides of adult human and pig erythrocytes.

Cytochalasin B and nitrobenzylthioinosine (NBMPR), which inhibit membrane transport of glucose and nucleosides, respectively, have served as photoaffinity ligands that become covalently linked at inhibitor binding sites on transporter-associated proteins. Thus, when membranes from erythrocytes of neonatal pigs with site-bound [3H]cytochalasin B or [3H]NBMPR were irradiated with uv light, two labeled membrane polypeptides (peak Mr values: 55,000 and 64,000, respectively) were identified. Treatment of the photolabeled membranes with endoglycosidase F increased the mobility of [3H]cytochalasin B- and [3H]NBMPR-labeled material (peak Mr values: 44,000 and 57,000, respectively) and limited digestion with trypsin yielded different polypeptide fragments (Mr values: 18,000-23,000 and 43,000, respectively).

Hemodynamic responses to different levels of alpha-adrenergic interruption in congestive heart failure.

The effects of prazosin, clonidine, and indoramin on central and regional hemodynamic parameters and left ventricular performance were analyzed in a congestive heart failure population to compare the pharmacodynamic responses to different levels of alpha-adrenergic interruption in this condition. The sympathetic nervous system is blocked at the peripheral alpha1-receptor by prazosin, at central nervous system alpha-receptor sites (via alpha-adrenoceptor agonism) by clonidine, and at peripheral and central sites by indoramin. Prazosin and indoramin produced reductions in total systemic and pulmonary vascular resistances, mean systemic and pulmonary artery pressures, and pulmonary capillary wedge pressure with little change in heart rate.