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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 217 records · Page 12Linked to original sources
PubMed1988

Selective protection from the inhibition by EEDQ of D1 and D2 dopamine agonist-induced rotational behavior in mice.

Mice with unilateral lesions of dopamine nigrostriatal neurons produced by injecting 6-hydroxydopamine into the striatum exhibited contralateral rotational behavior to the non-selective dopamine agonist apomorphine, the D1 dopamine agonist SKF 38393, and the D2 agonist quinpirole. The non-specific dopamine antagonist EEDQ blocked the circling responses to the three agonists. Pretreatment with specific, reversible dopamine antagonists before the EEDQ injection selectively prevented this blockade. Thus, if mice were pretreated with the D1 receptor antagonist SCH 23390 before EEDQ and the animals challenged with the D1 and D2 agonists 24 hours later, the rotational response to quinpirole was still inhibited, but the response to SKF 38393 was now evident. Similarly, in mice pretreated with the D2 receptor antagonist sulpiride before EEDQ and again challenged with the D1 and D2 agonists 24 hours later, the rotational response to SKF 38393 was still inhibited but the response to quinpirole was no longer inhibited. These results indicate that in vivo blockade of either D1 or D2 subpopulations of dopamine receptors may be achieved by selective protection with a reversible dopamine antagonist given prior to the administration of an irreversibly acting dopamine antagonist such as EEDQ.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Tartrazine.

Explore the source record for details and available documents.

Attention Deficit Disorder with Hyperactivity↗
PubMed1988

Quantitative perspectives on behavioral toxicology.

Behavioral endpoints offer special challenges to toxicology. One arises from the sometimes conflicting ways in which adverse effects may be expressed. For example, both increases and decreases in response rates of schedule-controlled performance may be produced by a specific agent, depending on the specific schedule. Interpretations of such an outcome depend upon a close analysis of the experimental circumstances and the behavioral findings. Another arises from the many disparate variables that can influence a particular outcome. Accurate measures of sensory thresholds, for instance, depend upon precise means for delivering stimuli and upon appropriate psychophysical procedures. Such examples emphasize that quantification in behavioral toxicology is more than a matter of attaching numbers to some arbitrarily selected measure. Instead, meaningful quantification first requires that the investigator understand in principle the sources of the measures to which the numbers are being attached. This is especially critical when the measures are being used not for the relatively straightforward purpose of hazard identification, but for the more subtle aim of risk assessment and dose-response (effect) extrapolation. For these aims, behavioral microanalyses, based on the coordination of multiple measures in individual subjects, usually provide the most robust guides.

Animals↗
PubMed1988

beta-Alanine auxotrophy associated with dfp, a locus affecting DNA synthesis in Escherichia coli.

Strains containing the conditional-lethal dfp-707 mutation, which have a defect in DNA synthesis at 42 degrees C, were found to require either pantothenate or its precursor, beta-alanine, for growth at 30 degrees C. The auxotrophy and conditional lethality were corevertible. Through localized mutagenesis of the dfp-pyrE region of Escherichia coli, another mutation, dfp-1, was obtained. It conferred the auxotrophy but not the conditional lethality of dfp-707. Complementation analysis, performed with a set of plasmid-borne deletion and insertion mutations, revealed a correspondence between the complementation of each mutant phenotype and the production of the dfp gene product, previously identified as a 45-kilodalton flavoprotein. The dfp mutants had a normal level of aspartate-1-decarboxylase, which is the only enzyme known to produce beta-alanine in E. coli and which is specified by the distant panD gene. A prototrophic pseudorevertant of a dfp-1 strain was found to have retained the dfp mutation, to be genetically unstable, and to have an elevated level of aspartate-1-decarboxylase, suggesting that it had acquired a duplication of panD. It is not known what steps in pantothenate or DNA metabolism are affected by the mutant dfp product or how its flavin moiety may be involved.

Alanine↗
PubMed1988

Lethality of a dut (deoxyuridine triphosphatase) mutation in Escherichia coli.

A chloramphenicol resistance gene was cloned into a plasmid-borne dut gene, producing an insertion mutation that was then transferred to the chromosome by allelic exchange. The mutation could not be acquired by haploid strains through substitutive recombination, even when two flanking markers were simultaneously transduced. The insertion was easily transferred, via generalized transduction, into the chromosomal dut region of strains harboring a lambda dut + transducing phage; however, the resulting dut mutant/lambda dut + merodiploid could not then be cured of the prophage. This apparent lethality of the mutation could not be explained by effects on adjacent genes; the dfp gene retained complementing activity, and a ttk insertion mutant was viable. The dut gene product, deoxyuridine triphosphatase, is known to reduce incorporation of uracil into DNA and to be required in the de novo synthesis of thymidylate. Therefore, an attempt was made to determine whether the dut insertion would be tolerated in strains carrying the following compensatory mutations: dcd (dCTP deaminase) and cdd (deoxycytidine deaminase), which should reduce dUTP formation; ung (uracil-DNA glycosylase), which should reduce fatally excessive excision repair; deoA (thymidine phosphorylase), which should enhance the utilization of exogenous thymidine; and sulA, which should reduce the lethal side effects of SOS regulon induction. These mutations, either alone or in various combinations, did not permit the survival of a haploid dut insertion mutant, suggesting that the dut gene product might have an essential function apart from its deoxyuridine triphosphatase activity.

DNA Mutational Analysis↗
PubMed1988

Behavior as an early indicator of pesticide toxicity.

Adverse behavioral effects are now a recognized outcome of exposure to many industrial and environmental chemicals. Pesticides occupy a special role, however, because so many of them, particularly insecticides, are designed specifically to act on neural tissue. The evaluation of behavioral toxicity is a new kind of challenge to pesticide toxicology because of the enormous structural and chemical heterogeneity of the nervous system and the even greater complexity of behavior. Determining that a particular agent is neurotoxic is not an overwhelming problem; even elementary screens are capable of detecting nervous system activity. The greater challenge is to evaluate toxicity in the context of risk assessment, which requires techniques and experimental protocols capable of detecting the subtle manifestations that tend to appear early in the course of a toxic process. A combination of advanced behavioral methods, coupled with an emphasis on tracing the responses of individual organisms, is often optimal for achieving such a goal.

Animals↗
PubMed1988

Aminothiols: synthesis and effect on chicken brain aminopeptidases.

An amino acid derivative, leucinethiol, was reported to be a strong inhibitor of aminopeptidase activity. In order to obtain selective inhibitors of various brain aminopeptidases, we tested the inhibition by amino acid analogs of brain aminopeptidase activity. In particular, we synthesized the trifluoroacetyl derivatives of phenylalaninol, tyrosinol, and leucinol; leucinethiol; and phenylalaninethiol and measured their effect on soluble puromycin-sensitive aminopeptidase S1 and SII purified in our laboratory. Two of the compounds, L-bis (1-thio-2-amino-4-methylpentane) dihydrochloride (TAMP) and L-bis (1-thio-2-amino-3-phenylpropane) dihydrochloride (TAPP), caused significant inhibition.

Amphetamines↗
PubMed1987

Shear creep of injectable collagen biomaterials.

Shear creep experiments in a parallel-plate apparatus were carried out on two injectable forms of collagen: semidilute nonfibrillar solutions (32 and 45 mg protein/mL) and aqueous fibrillar suspensions (at 35 and 65 mg/mL). Nonfibrillar solutions were more easily deformed than fibrillar suspensions, and both materials continued to deform slowly, even at long times (up to 6 X 10(4) sec). When the creep compliance, J(t), was plotted versus t1/3, regions of linear dependence were identified, which indicated that the materials were undergoing Andrade creep. At higher stress levels, J(t) diverged from t1/3, and true viscous flow occurred. A delayed viscosity could be calculated which agreed with viscosities derived from measurements under conditions of steady shear Couette flow. The time of onset of viscous flow was identified with a specific strain for each material, suggesting yield strain behavior. An analysis of recovery curves showed that at low stress levels or for short experimental times, the Boltzmann superposition was approximately obeyed, indicating linear behavior. At high stress levels and times greater than 10(3) sec, both nonfibrillar solutions and fibrillar suspensions showed marked curvature of stress-strain curves, which indicated that the materials are nonlinear in creep.

Animals↗
PubMed1987

Differential effects of fluphenazine-N-mustard, on calmodulin activity and on D1 and D2 dopaminergic responses.

Fluphenazine-N-mustard (FNM) has been shown to irreversibly block dopaminergic receptor sites and inhibit certain dopaminergically-mediated behaviors. In this study we measured whether FNM has any differential effects on D1 and D2 dopaminergic events. Accordingly, we examined the relative effects of FNM on rotational behavior induced by SKF 38393 (D1 agonist) and Ly 171555 (D2 agonist) in mice with unilateral, 6-hydroxydopamine-induced lesions of the striatum and the effects of FNM on the binding of [3H]Sch 23390 (D1 ligand) and [3H]spiroperidol (D2 ligand) to mouse striatal membranes. FNM inhibited rotational behavior induced by Ly 171555 at doses 10-fold lower than those required to block rotations induced by SKF 38393 (ID50 values: Ly 171555 = 1.8 mumole/kg, IP; SKF 38393 = 16 mumole/kg, IP). The inhibitory effect of high doses of FNM (20 mumole/kg) on rotational behavior was overcome by increasing the dose of SKF 38393 and apomorphine, a nonselective dopaminergic agonist. By contrast, the inhibitory effect of FNM was not overcome by Ly 171555, even when given in doses more than 100 times its ED50. Using striatal homogenates in vitro, FNM inhibited the specific binding of [3H]spiroperidol at concentrations about 10-fold lower than those required to inhibit the binding of [3H]Sch 23390 (IC50 values: [3H]spiroperidol = 90 nM; [3H]Sch 23390 = 840 nM). Considerably higher concentrations of FNM were needed to irreversibly inhibit calmodulin activity in striatal homogenates (IC50 = 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Comparison of the effects of fluphenazine-N-mustard on dopamine binding sites and on behavior induced by apomorphine in supersensitive mice.

The effects of fluphenazine-N-mustard (FNM) on the binding of [3H]spiroperidol both in vitro and in vivo and on behavior produced by apomorphine were examined in mice. In vitro, FNM inhibited the binding of [3H]spiroperidol to membranes from the striatum in the mouse, with an IC50 of approximately 100 nM. In vivo administration of FNM resulted in a dose-dependent inhibition of the subsequent binding of [3H]spiroperidol with an ED50 of approximately 20 mumol/kg, (i.p.). To examine whether or not this interaction was irreversible, FNM was preincubated with striatal homogenates in vitro or administered in vivo; the striata were subsequently homogenized, washed extensively to remove reversibly bound FNM and then assayed by measuring the binding of [3H]spiroperidol to these washed membranes. The results showed that FNM caused a 50-60% blockade of the binding sites, suggesting that FNM irreversibly inhibits binding sites for spiroperidol. Studies of the effects of FNM on the function of dopamine showed that prior administration of FNM blocked the apomorphine-induced rotational behavior in mice with unilateral lesions of the striatum produced by 6-hydroxydopamine; the ED50 was 0.8 mumol/kg, (i.p.), a dose which was about 100-fold less than that found to inhibit the binding of [3H]spiroperidol by 50%. Half-maximum recovery of behavior occurred 4 days after the injection of FNM (20 mumol/kg, i.p.). Under similar circumstances, full recovery of the binding of [3H]spiroperidol occurred within 1 day. These data suggest that FNM interacts irreversibly with binding sites for [3H]spiroperidol, but the magnitude of this interaction was not predictive of its behavioral efficacy.

Animals↗
PubMed1987

The clearance of manganese chloride in the primate.

Two macaque monkeys inhaled trace amounts of 54MnCl2 for 30 min. Subsequently the chest, head, and fecal radioactivity were monitored for over a year. The chest data curve required a sum of three exponential terms, with half-times ranging from 0.2 to 187 days, to attain a satisfactory fit. Head levels peaked 40 days after acute inhalation exposure and remained elevated for over a year. The excretion of manganese through the feces was best described by a sum of two exponentials. One had a half-time of less than 1 day and the second had a half-time of 50 to 60 days. A third macaque received a 6-week continuous exposure to 54Mn through a subcutaneous osmotic pump. With this route, manganese clearance from the head occurred at a faster rate than after acute inhalation exposure. Fecal elimination following continuous subcutaneous exposure resembled that following acute inhalation. Kinetic analyses suggested that the long half-times of manganese in the head following inhalation reflected both slow disappearance from the head and replenishment from other depots.

Animals↗