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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 235 records · Page 13Linked to original sources

Endonuclease IV of Escherichia coli is induced by paraquat.

The addition of paraquat (methyl viologen) to a growing culture of Escherichia coli K-12 led within 1 hr to a 10- to 20-fold increase in the level of endonuclease IV, a DNase for apurinic/apyrimidinic sites. The induction was blocked by chloramphenicol. Increases of 3-fold or more were also seen with plumbagin, menadione, and phenazine methosulfate. H2O2 produced no more than a 2-fold increase in endonuclease IV activity. The following agents had no significant effect: streptonigrin, nitrofurantoin, tert-butyl hydroperoxide, gamma rays, 260-nm UV radiation, methyl methanesulfonate, mitomycin C, and ascorbate. Paraquat, plumbagin, menadione, and phenazine methosulfate are known to generate superoxide radical anions via redox cycling in vivo. A mutant lacking superoxide dismutase was unusually sensitive to induction by paraquat. In addition, endonuclease IV could be induced by merely growing the mutant in pure O2. The levels of endonuclease IV in uninduced or paraquat-treated cells were unaffected by mutations of oxyR, a H2O2-inducible gene that governs an oxidative-stress regulon. The results indicate that endonuclease IV is an inducible DNA-repair enzyme and that its induction can be mediated via the production of superoxide radicals.

Anaerobiosis↗

Impact of chickenpox on households of healthy children.

There is little information available regarding the impact of varicella among healthy children. A group of 137 households, identified by the County of Los Angeles Department of Health Services, were interviewed by telephone and yielded 247 cases of varicella. There were no hospitalizations for complications. Rates for physician visits and telephone calls to health care providers were 0.5 and 1.0 per case, respectively. School days lost by cases and work days lost by well adults in the households were 8.7 and 0.5 per case, respectively. Varicella had a measurable impact of economic significance on our survey population. Our observations need to be extended and included in cost-benefit analyses of varicella vaccine.

Absenteeism↗

Environmental contaminants and behavior disorders.

The discipline of behavioral toxicology is an acknowledgement that behavioral assessments should play a role in judging the safety of chemicals. Such a role is emphasized by the toxicological history of many different classes of substances. These include metals, insecticides, volatile organic solvents, and even food additives. For all of these, incipient toxicity often takes the form of subjective complaints that are later followed by overt impairments. The fetus and young child seem to be at special risk for substances such as methylmercury and synthetic food colors, a susceptibility not fully recognized.

Animals↗

Differential inhibition of calmodulin-sensitive phosphodiesterase and Ca++-adenosine triphosphatase by chlorpromazine-linked calmodulin.

Upon irradiation with UV light, chlorpromazine binds irreversibly to calmodulin and inactivates it. To determine whether this chlorpromazine-calmodulin (CPZ-CaM) complex can inhibit the actions of native calmodulin, we examined its effects on the activity of calmodulin-sensitive cyclic nucleotide phosphodiesterase from rat brain and on the Ca++-adenosine triphosphatase (ATPase) of human erythrocyte membranes. The CPZ-CaM complex was prepared by irradiating purified bovine brain calmodulin in the presence of chlorpromazine and Ca++. The sample was then dialyzed extensively to remove reversibly bound chlorpromazine and then assayed for its ability to activate calmodulin-sensitive phosphodiesterase and Ca++-ATPase, and for its ability to block the stimulatory effects of native calmodulin on these enzymes. The CPZ-CaM complex had no effect on the basal activity of either enzyme; it neither activated nor inhibited the enzymes when assayed in the absence of calmodulin. However, it affected differentially the activation of the two enzymes by native calmodulin. The CPZ-CaM complex totally inhibited calmodulin-stimulated phosphodiesterase but had no effect on the activation of the ATPase by calmodulin. Other studies showed that CPZ-CaM increased the activation constant (Ka) for the interaction of calmodulin with phosphodiesterase but did not affect the maximal activation (Vmax) of the enzyme by calmodulin. Neither calmodulin nor CPZ-CaM altered the Km for the interaction between phosphodiesterase and cyclic AMP. These results suggest that CPZ-CaM inhibits the calmodulin-induced activation of phosphodiesterase by competing with calmodulin for regulatory sites on the enzyme and not by interacting with calmodulin itself or by blocking the interaction of cyclic AMP with the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy.

After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

Animals↗

Effect of several amino acid phosphonates and related compounds on rat brain aminopeptidases.

N-Terminal sodium phosphonate derivatives Na3O3PCH2CONHR (R-Leu, Phe, or Tyr) and Na3O3PCH2CONHR-R (R-R = Leu-Phe, Phe-Leu, Phe-Phe, and Phe-Tyr) were synthesized. All showed no activity toward a soluble rat brain aminopeptidase. We could not prepare the corresponding N-2-phosphono-2,2-diphenylacetyl compounds (Na3O3PC(C6H5)2CONHR) by the same Arbusov reaction. Little or no inhibition was obtained with the N-(2-hydroxy-2,2-diphenylacetyl derivatives HOC(C6H5)2CONHR (R = Leu, Phe, Trp, or Tyr). The best inhibitory responses were given by the N-(2-halogeno-2,2-diphenylacetyl mono- and dipeptides (Br/Cl)C(C6H5)2CONH Phe and (Br/Cl)C(C6H5)2CONHR-R (R-R = Leu,Leu, Leu-Phe, Phe-Gly, Phe-Leu, or Phe-Phe), respectively.

Amino Acids↗

Neonatal behavioral toxicity in rats following prenatal exposure to methanol.

Although methanol (MEOH) may assume a significant role as a fuel, which implies wide availability, little is known of its toxicity apart from acute poisoning episodes in human adults. Even less is known about its toxicity in developing organisms. This experiment studied the early behavioral development of rats whose mothers had consumed MEOH during gestation by measuring the responses of suckling (postnatal day 1) and nest-seeking (postnatal day 10). Primigravida Long-Evans rats were divided into three groups (N = 10). Two of the groups consumed drinking solutions of 2% MEOH instead of distilled water either on gestational days 15-17 (MEOH 1) or 17-19 (MEOH 2). No maternal toxicity was apparent as measured by weight gain, gestational duration, and daily fluid intake. Daily MEOH consumption averaged 2.5 gm/kg over the 3-day period in both MEOH groups. Litter size, birth weight, and infant mortality did not differ among the three groups. Postnatal growth and date of eye opening were unaffected. MEOH pups required longer than controls to begin suckling on postnatal day 1. On postnatal day 10, they required more time to locate nesting material from their home cages. These data suggest that prenatal MEOH exposure induces behavioral abnormalities early in life that are unaccompanied by overt toxicity.

Animals↗

Operant behavior in transition reflects neonatal exposure to cadmium.

Male Long-Evans rats were injected with 0, 1, 3, or 6 mg/kg of cadmium chloride on the first day of life. Animals free of morphological stigmata at weaning were selected for study. Tissue concentrations of cadmium and operant behavior under various fixed-ratio (FR) schedules of reinforcement were evaluated when these rats were adults. Dose-related increases in cadmium were present in the brains, livers, and kidneys. Dose-related differences in behavior were most evident during the transition from fixed ratio 25 (FR 25 or 25 responses/reinforcer) to FR 75. An inverted U describes the relationship between response output during the transition to FR 75 and cadmium chloride dose response output increased at 3 mg/kg and decreased at 6 mg/kg. The rate decreases were not correlated with weight loss that appeared after some of the animals exposed to 6 mg/kg reached 60 days of age. Challenge doses of d-amphetamine revealed no interaction between neonatal exposure to cadmium and d-amphetamine. The occurrence of alterations in operant behavior in animals that appeared normal on a number of preweaning evaluations suggests that operant behavior in transition was sensitive to subtle effects not observed with other commonly used tests. The data provide evidence for delayed effects in the adult that are due to neonatal exposure to cadmium.

Animals↗

Peers' granting of control to women with different sex role identities: implications for depression.

This investigation is one of a series of studies seeking to determine the degree of control given to women with different sex role identities. This study focused on the extent to which peers were willing to grant control to women with different sex role identities if working individually with each woman on various two-person tasks. The results indicated that women with different sex role identities were granted different amounts of control by their peers as a function of the type of two-person task under consideration. Women rated high on masculinity were granted greater control on enjoyable and creative tasks, whereas women rated low in masculinity were given more control on methodical and less enjoyable tasks. Women judged high in femininity were given control on tasks requiring interpersonal skills. These findings were discussed within the context of learned helplessness theory as a possible aid in understanding why more women than men become depressed.

Adult↗

Endonuclease IV (nfo) mutant of Escherichia coli.

A cloned gene, designated nfo, caused overproduction of an EDTA-resistant endonuclease specific for apurinic-apyrimidinic sites in DNA. The sedimentation coefficient of the enzyme was similar to that of endonuclease IV. An insertion mutation was constructed in vitro and transferred from a plasmid to the Escherichia coli chromosome. nfo mutants had an increased sensitivity to the alkylating agents methyl methanesulfonate and mitomycin C and to the oxidants tert-butyl hydroperoxide and bleomycin. The nfo mutation enhanced the killing of xth (exonuclease III) mutants by methyl methanesulfonate, H2O2, tert-butyl hydroperoxide, and gamma rays, and it enhanced their mutability by methyl methanesulfonate. It also increased the temperature sensitivity of an xth dut (dUTPase) mutant that is defective in the repair of uracil-containing DNA. These results are consistent with earlier findings that endonuclease IV and exonuclease III both cleave DNA 5' to an apurinic-apyrimidinic site and that exonuclease III is more active. However, nfo mutants were more sensitive to tert-butyl hydroperoxide and to bleomycin than were xth mutants, suggesting that endonuclease IV might recognize some lesions that exonuclease III does not. The mutants displayed no marked increase in sensitivity to 254-nm UV radiation, and the addition of an nth (endonuclease III) mutation to nfo or nfo xth mutants did not significantly increase their sensitivity to any of the agents tested.

Alkylating Agents↗

Determinants of behavioral response with ozone exposure.

Three separate experiments were performed to evaluate how the topography of a behavioral response and its consequences influence the behavioral effects produced by ozone (O3) exposure. The first experiment measured the responding of food-deprived rats working to obtain intermittent delivery of small pellets of food by completing an active response, wheel running. Low O3 concentrations (0.12 ppm) reduced the frequency of running responses maintained by this fixed-interval 10-min schedule of food delivery. The second experiment examined the effects of O2 on food-deprived rats performing a response (nose poking) that required minimal physical effort to produce deliveries of food pellets. Rats in this situation began to show reductions in responding at 0.5 ppm O3. A third experiment showed that responses requiring minimal physical effort, such as lever pressing, can be a sensitive index of O3 exposure if the response provides access to wheel running. We concluded that increased physical activity during exposure appeared to be an important variable in determining sensitivity to O3 exposure.

Animals↗

Reversal of supersensitive apomorphine-induced rotational behavior in mice by continuous exposure to apomorphine.

Mice with unilateral lesions of the nigrostriatal dopaminergic neurons, induced by an intrastriatal injection of 6-hydroxydopamine, respond to an acute injection of apomorphine by rotating in a direction contralateral to the lesion. The dose of apomorphine that produced a half-maximal turning response was 0.4 mumol/kg s.c.; maximal turning responses were seen at 2 mumol/kg s.c. This behavioral supersensitivity may be due to an increased density of dopaminergic receptors. To determine whether continuous stimulation of these receptors with a dopaminergic agonist would reverse the dopaminergic behavioral supersensitivity, mice were exposed to continuous infusion of apomorphine via a s.c. implanted osmotic minipump containing 150 mumol of apomorphine in 0.2 ml and then challenged with an acute injection of apomorphine (2 mumol/kg s.c.) at varying times after the implant. Initially, the mice displayed spontaneous rotational behavior beginning by 1 hr after implantation, but this spontaneous behavior diminished over time and was absent by 4 days after implantation. The turning response of mice challenged with an acute injection of apomorphine was significantly reduced at 1 day after the chronic implantation and was totally absent at 2 and 4 days after implantation. This effect of continuous exposure to apomorphine was found to be concentration- and time-dependent; mice implanted with pumps containing 75 mumol of apomorphine required 8 days of exposure for tolerance to develop. Upon removal of the apomorphine-containing implants, the supersensitive rotational behavior returned over a 7-day period, with 50% recovery occurring at 2 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Toxic chemical disasters and the implications of Bhopal for technology transfer.

The dramatic disaster in 1984 at Bhopal, India, may be overshadowed in total impact by less immediate health effects characterized by long latency, cumulative damage, and subtle impairments. Transfer of chemical technology must be accompanied by transfer of the corresponding infratechnology, toxicology, only then can the process of technology transfer be managed with fewer risks, fewer costs, and fewer tragic surprises.

Accidents, Occupational↗

Effect of several amino acid phosphonates and other compounds on rat brain and kidney peptidases.

A series of N-terminal phosphonate derivatives, H2O3PCHPhNHR (R = Leu, Phe, Trp, and/or Tyr), were synthesized with the aim of mimicking phosphoramidon, a potent inhibitor of enkephalinase, while avoiding the lability of the scissile P-N bond. All of the N-phosphonobenzyl derivatives of the amino acids, including the substituted succinylhydrazobenzophenone compounds, were inactive toward rat brain aminopeptidase and rat kidney carboxypeptidase. The N-monobenzylphosphonobenzyl derivatives, PhCH2OPO(OH)CHPhNHR, of individual amino acids and several of the N-phosphonobenzyl dipeptides showed inhibition in the micromolar range toward the soluble exopeptidase but were inactive with both the brain and kidney endopeptidase.

Aminopeptidases↗