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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Triazolam blocks the initial rotational effects of quinpirole but permits the later developing reduction of dopamine D2-mediated rotational behavior and dopamine D2 receptors.

Continuous infusion of the dopamine D2 receptor agonist quinpirole into mice with unilateral striatal 6-hydroxydopamine lesions initially produces a supersensitive rotational behavior. This is followed by reductions of dopamine D2-mediated behavior and dopamine D2 receptors. In this study we attempted to determine if it is possible to inhibit the acute increase in D2-mediated behavior while still allowing the reduction of D2-mediated behavioral responses and dopamine D2 receptors to occur. Mice were implanted with Alzet minipumps containing either quinpirole alone or quinpirole combined with the GABA receptor modulator triazolam or the dopamine D2 receptor antagonist sulpiride, and rotational behavior was monitored for the 6 days of infusion. The pumps were then removed, and D2 receptors in striatal membranes were determined. Triazolam completely blocked the initial rotational behavior normally induced by implanting quinpirole. However, the quinpirole-induced reduction of D2-mediated behavioral responses and D2 receptors still occurred. Continuous infusion of sulpiride also inhibited the rotational behavior produced by quinpirole, but it prevented the reduction of dopamine D2 receptors. We conclude that up-regulated dopamine receptors and dopaminergic behaviors can be reversed by the continuous administration of a dopamine receptor agonist and that this reversal can occur without producing an initial exacerbation of dopaminergic responses. These results suggest that this type of treatment regimen might be useful for treating clinical conditions associated with dopaminergic supersensitivity.

Analysis of Variance↗
PubMed1992

Cyclic AMP selectively up-regulates calmodulin genes I and II in PC12 cells.

Calmodulin is encoded by three genes in rat tissues, which collectively transcribe five different mRNAs. We showed previously that the pheochromocytoma cell line, PC12, expresses all five of these mRNAs and that treating PC12 cells with nerve growth factor differentially induces the calmodulin mRNAs; the greatest increase was seen by 24 h in the 1.4 kb transcript from calmodulin gene II. In the present study we found that treating PC12 cells with dibutyryl cyclic AMP also differentially increased the levels of the calmodulin mRNAs. However, dibutyryl cyclic AMP produced increases as early as 3 to 6 h, with the greatest increase (about 3-fold) being seen in the level of the 1.7 kb mRNA transcribed from calmodulin gene I. The transcripts of 4.1 kb (calmodulin gene I) and 1.4 kb (calmodulin gene II) were also increased, but the 2.3 kb transcript from calmodulin gene III remained stable. Another cyclic AMP analogue, chlorophenylthio cyclic AMP, produced effects similar to those of dibutyryl cyclic AMP, but dibutyryl cyclic GMP did not. Pretreatment with cycloheximide blocked the increase in the 4.1 kb calmodulin mRNA induced by dibutyryl cyclic AMP, but only partially blocked the increase in the 1.4 kb and 1.7 kb transcripts. Phorbol 12-myristate 13-acetate, which can induce some cyclic AMP responsive genes, failed to significantly change the levels of any of the calmodulin mRNAs. These studies show that, like nerve growth factor, cyclic AMP can selectively up-regulate the transcripts from calmodulin genes in PC12 cells, but the time-course and type of transcripts induced by cyclic AMP are distinct. These results suggest that the mechanisms by which these two agents alter the calmodulin transcripts are different.

Animals↗
PubMed1992

Comparative lethality of methanol, ethanol and mixtures in female rats.

The lethalities of pure methanol and pure ethanol were compared to two mixtures of ethanol/methanol with the following percentages (95/5% and 65/35% v/v). This study was conducted to simulate situations of human exposure to denaturated alcohol (by 5% methanol) or adulterated alcohol (by 35% methanol). Four groups of female adult virgin albino rats were treated with the four mixtures. A fifth group was used as a vehicle control. Graded oral doses were given to eight animals per dose. Lethality over 24 h was used as an end-point. The LD50 was calculated for each of the four treatments on a molar basis. A dose-response function for each mixture was plotted of percentage lethality vs. mmol kg-1 equivalent to the given ml kg-1 dose. Results showed a significantly different LD50 estimates (P less than 0.03) for the four mixtures. The order of lethal toxicity was as follows: 95/5% methanol/ethanol, pure methanol, pure ethanol then 65/35% methanol/ethanol. Slope comparisons indicated two pairs: 65/35% ethanol/methanol and pure ethanol yielding a steep slope, and 95/5% ethanol/methanol and pure methanol yielding a shallow slope. These data indicated that the acute lethality of ethanol/methanol mixtures is a complex unpredictable function. This toxicity presumably depends in a complicated way on the differences in the effective molecular weights of the two alcohols in each of the mixtures.

Animals↗
PubMed1992

Persistent effects of manganese on effortful responding and their relationship to manganese accumulation in the primate globus pallidus.

Manganese produces signs and symptoms that suggest involvement of the basal ganglia, especially the globus pallidus and substantia nigra. Overt neurological signs have been reported in primates exposed to high levels of manganese (over 100 mg/kg) but little is known about the effects of lower doses. To examine these issues, three cebus monkeys were trained to operate a response device with their arms and legs by executing a rowing-like movement against a 3.9- to 4.1-kg spring through an arc length of 10 cm under a multiple fixed-ratio fixed-interval schedule of reinforcement. Over the course of 450 days, these monkeys were administered acute doses of 5 or 10 mg/kg iv of manganese chloride using a multiple baseline experimental design. Doses as low as 5 mg/kg provoked a large increase in the number of incomplete responses. The onset of manganese's effect appeared within days of exposure and developed over the course of several weeks. Its magnitude declined over the course of months, but after a cumulative dose of 10 to 40 mg/kg it did not return to baseline. Action tremor appeared at cumulative doses greater than 40 mg/kg and dystonia was never observed at the cumulative doses examined. Behavioral microanalysis revealed that manganese's effects initially appeared as increased variability of interresponse times and response duration. Later, the response pattern during the fixed ratio component shifted to one of progressively increasing durations through the course of the ratio. Magnetic resonance imaging revealed that the behavioral effects of manganese corresponded to an apparent increase in the manganese content of the globus pallidus and substantia nigra.

Animals↗
PubMed1992

Developmental and age-related changes in the D2 dopamine receptor mRNA subtypes in rat brain.

The influence of ontogeny and aging on the D2 dopamine receptor mRNA in rat brain were examined using in situ hybridization histochemistry and Northern analysis utilizing oligonucleotide probes complementary to the different D2 mRNA subtypes. At birth, there was a high level of D2 dopamine receptor mRNA in corpus striatum relative to that found in the cerebral cortex and other brain areas. The hybridization signal of striatum (using a probe that hybridizes to both the D2A and D2B mRNA) increased during the first two postnatal weeks, reached a peak at day 16, then declined slightly. The D2A mRNA showed a similar distribution and developmental pattern. Intracisternal injection of 6-hydroxydopamine into neonates did not significantly alter the increase of the D2 dopamine receptor mRNAs, suggesting that neuronal input does not influence the ontogenetic development of this mRNA. In striatum, olfactory tubercule and inferior colliculus, the D2A mRNA declined between 3 and 24 months of age. By contrast, there was an age-related increase in the D2A mRNA in the anterior and intermediate lobes of the pituitary. The mRNA for the D2B dopamine receptor showed very low but nevertheless detectable levels in striatum, olfactory tubercule and pituitary. Like with the D2A mRNA, in 24-month-old rats the D2B mRNA declined in striatum and olfactory tubercule and increased in pituitary. These results show that there are differential tissue-related changes in the mRNAs for the D2 dopamine receptor during both development and aging.

Aging↗
PubMed1992

The lab versus the clinic. Effects of child and adolescent psychotherapy.

Four recent meta-analyses, involving more than 200 controlled outcome studies, have shown consistent evidence of beneficial therapy effects with children and adolescents. However, most of the studies involved experimental procedures, nonreferred subjects, specially trained therapists with small caseloads, and other features that may not represent conventional clinic therapy. Research focused on more representative treatment of referred clients in clinics has shown more modest effects; in fact, most clinic studies have not shown significant effects. Interpretation studies have not shown significant effects. Interpretation of these findings requires caution; such studies are few and most could profit from improved methodology. The clinic studies do raise questions as to whether the positive lab findings can be generalized to the clinics where most therapy occurs; however, the lab interventions that have worked so well may point the way to enhanced therapy effects in clinics.

Adolescent↗
PubMed1992

Relations among self-reported depressive symptoms in clinic-referred children versus adolescents.

Although there is consensus regarding the existence of childhood depression, disagreement remains as to whether symptoms are developmentally isomorphic. Previous studies focused on developmental differences in symptom levels; analyses of relations among symptoms may be more appropriate, however. Here both approaches were used to compare the Children's Depression Inventory responses from 1,030 clinic-referred children and adolescents. Four of nine symptom categories showed significant developmental differences in their correlations with total score. Externalizing behavior and guilt were more strongly related to depression in children than adolescents; affective symptoms and concerns about the future showed the reverse pattern. Results illustrate the importance of considering relations among symptoms as well as differences in symptom levels when evaluating theoretical claims about developmental differences in the nature of clinical syndromes.

Adolescent↗
PubMed1992

Some consequences of early harsh discipline: child aggression and a maladaptive social information processing style.

Although a number of studies have reported a relation between abusive parental behavior and later aggressive behavior in the victim, many of these investigations have had methodological limitations that make precise interpretation of their results problematic. In the present study, we attempted to determine whether harsh parental discipline occurring early in life was associated with later aggression and internalizing behavior in children, using a prospective design with randomly selected samples to avoid some of these methodological difficulties. Structural equation modeling indicated a consistent relation between harsh discipline and aggression in 2 separate cohorts of children. This relation did not appear to be due to possible confounding factors such as child temperament, SES, and marital violence, although there was some indication in our data that the latter variables were related to child aggression. In addition, our analyses suggested that the effect of harsh discipline on child aggression may be mediated at least in part by maladaptive social information processing patterns that develop in response to the harsh discipline.

Adaptation, Psychological↗
PubMed1992

Two-stage induction of the soxRS (superoxide response) regulon of Escherichia coli.

soxR and soxS are adjacent genes that govern a superoxide response regulon. Previous studies revealed that induction of the regulon is accompanied by increased transcription of soxS, which can activate the target genes. Therefore, induction may occur in two stages: the soxR-dependent activation of soxS, followed by the soxS-dependent induction of other genes. However, the requirement for soxR was unproven because the only existing soxR mutations either were of the regulon-constitutive type or also involved soxS. Therefore, we produced an insertion mutation that was shown by complementation to inactivate only soxR. In confirmation of the two-stage model, soxR was required for the induction by paraquat of the target genes studied (nfo, zwf, and sodA), for paraquat resistance, and for the 47- to 76-fold induction of soxS-lacZ gene fusions. Paraquat did not affect the expression of soxR-lacZ gene fusions. In a soxRS deletion mutant, the regulon was constitutively activated by a runaway soxS+ plasmid. However, a lower-copy-number plasmid failed to activate nfo, zwf, or sodA but did increase the paraquat resistance of a soxRS mutant. Therefore, there is a differential response of the regulon genes to soxS overproduction. A soxR regulon-constitutive mutation was suppressed by a soxR+ plasmid, suggesting a competition between native and activated forms of SoxR. It is proposed that to enhance the sensitivity of the response, the cell minimizes such potential competition by manufacturing only a small amount of this sensor protein, thereby necessitating signal amplification via induction of soxS.

Bacterial Proteins↗
PubMed1992

Multiple mutant of Escherichia coli synthesizing virtually thymineless DNA during limited growth.

The dut gene of Escherichia coli encodes deoxyuridine triphosphatase, an enzyme that prevents the incorporation of dUTP into DNA and that is needed in the de novo biosynthesis of thymidylate. We produced a conditionally lethal dut(Ts) mutation and isolated a phenotypic revertant that had a mutation in an unknown gene tentatively designated dus (for dut suppressor). The dus mutation restored the ability of the dut mutant to grow at 42 degrees C without restoring its enzymatic activity or thymidylate independence. A strain was constructed bearing, in addition to these mutations, ones affecting the following genes and their corresponding products: ung, which produces uracil-DNA N-glycosylase, a repair enzyme that removes uracil from DNA; deoA, which produces thymidine (deoxyuridine) phosphorylase, which would degrade exogenous deoxyuridine; and thyA, which produces thymidylate synthase. When grown at 42 degrees C in minimal medium containing deoxyuridine, the multiple mutant displayed a 93 to 96% substitution of uracil for thymine in new DNA. Growth stopped after the cellular DNA had increased 1.6- to 1.9-fold and the cell mass had increased 1.7- to 2.7-fold, suggesting a general failure of macromolecular biosynthesis. DNA hybridization confirmed that the uracil-containing DNA was chromosomal and that new rounds of initiation must have occurred during its synthesis.

DNA Glycosylases↗
PubMed1992

dcd (dCTP deaminase) gene of Escherichia coli: mapping, cloning, sequencing, and identification as a locus of suppressors of lethal dut (dUTPase) mutations.

In Escherichia coli, most of the dUMP that is used as a substrate for thymidylate synthetase is generated from dCTP through the sequential action of dCTP deaminase and dUTPase. Some mutations of the dut (dUTPase) gene are lethal even when the cells are grown in the presence of thymidine, but their lethality can be suppressed by extragenic mutations that can be produced by transposon insertion. Six suppressor mutations were tested, and all were found to belong to the same complementation group. The affected gene was cloned, it was mapped by hybridization with a library of recombinant DNA, and its nucleotide sequence was determined. The gene is at 2,149 kb on the physical map. Its product, a 21.2-kDa polypeptide, was overproduced 1,000-fold via an expression vector and identified as dCTP deaminase, the enzyme affected in previously described dcd mutants. Null mutations in dcd probably suppress the lethality of dut mutations by reducing the accumulation of dUTP, which would otherwise lead to the excessive incorporation of uracil into DNA.

Amino Acid Sequence↗
PubMed1992

Interactions between ethanol and pantothenic acid on tremor and behavior in squirrel monkeys.

Ethanol consumption alters the levels and distribution of pantothenic acid and its metabolic products, an effect that can be counteracted by preloading with pantothenic acid. Ethanol also produces significant disturbances in motor function and has a potent tremorolytic activity when administered acutely. To investigate the interaction of pantothenic acid and ethanol, the two substances were administered alone and in combination to three squirrel monkeys trained to perform a response-initiated positioning task that enabled the detection of tremor. Tremor was evaluated using spectral analytical techniques. Ethanol at 1.0 gm/kg produced a tenfold reduction in tremor over control sessions while pantothenic acid alone had no effect on tremor. Pantothenic acid (200 mg/kg, IP or IV) administered before ethanol intubation completely counteracted the tremor-reducing action of ethanol in two monkeys and partially counteracted it in a third. The interaction between pantothenic acid and ethanol was limited to these motor effects; the rate-reducing effect of ethanol was unaffected by pantothenic acid.

Animals↗
PubMed1992

[Logistics of antidotes in Switzerland].

Antidotal compounds are principally classified into three groups. The most important compounds are available in all hospitals and pharmacies. They guarantee the basic supply of antidotes in all part of Switzerland. More specific antidotes are constantly available in 24 regional centres, some of which being further specialized in certain areas (e.g. Cantonal Pharmacy of Zurich: anti-venoms and radionucleotide-antidotes). Ongoing routine collaboration between the Swiss Toxicological Information Centre (STIC) and the Swiss Association of Hospital Pharmacists (GSASA) is important for continuous and competent information about the availability of newly developed antidotal drugs in Switzerland.

Antidotes↗
PubMed1991

Ontogenetic expression of D2 dopamine receptor mRNA in rat corpus striatum.

The ontogenetic expression of the D2 dopamine receptor (D2R) mRNA has been characterized in rat corpus striatum by in situ hybridization histochemistry and Northern and slot blot analyses using oligonucleotide probes directed toward either the D2R-A subtype of the D2R mRNA or to both the D2R-A and D2R-B subtypes of the D2R mRNA. The results showed that both D2R mRNAs were detected in rat striatum at birth, gradually increased until day 16 postnatally (P16), then declined slightly. At early stages of development, the hybridization signal, when viewed under low magnification, was fairly evenly distributed throughout the striatum. However, later in development (P16) a cluster pattern became manifest. Autoradiographic studies using the mu-opiate receptor as an indication of striatal 'patches' in serial, adjacent sections of striatum indicated that the cluster pattern of the D2R mRNA was not associated solely with the patch or matrix compartments of the striatum. A cellular analysis showed that at early developmental stages the quantity of D2R mRNA per cell was very low in striatum. During the first two postnatal weeks, certain subpopulations of striatal neurons evidenced a marked increase in the expression of D2R mRNA per cell. Administration of 6-hydroxydopamine into neonatal rats failed to significantly change the developmental profile of D2R mRNA in the rat striatum of 16- and 32-day-old animals, although the same treatment caused a marked increase in proenkephalin mRNA. These results suggest that the postnatal development of the D2R mRNA in rat striatum correlates well with the ontogeny of the D2 dopamine receptor, that the developmental expression of the D2R mRNA is highly associated with the maturation and differentiation of striatal neurons, and that the development of the D2R mRNA in rat striatum, unlike that of proenkephalin mRNA, can proceed even with reduced dopaminergic afferent input from the substantia nigra.

Animals↗
PubMed1991

The increase of calmodulin in PC12 cells induced by NGF is caused by differential expression of multiple mRNAs for calmodulin.

A rat pheochromocytoma cell line (PC12 cells) was used as a model to investigate the role of calmodulin and its multiple mRNAs in NGF-induced neuronal differentiation. The effect of NGF on the degree of differentiation was assayed using a simple differentiation scoring system. Significant increases in the differentiation score were seen by one day, and the scores increased about 10-fold by 8 days of treatment. NGF also increased calmodulin in the PC12 cells; significant increases were seen by 2 days of treatment, and a maximum increase of 3-fold was seen by 4 days. Northern blot analysis using a calmodulin riboprobe revealed that all five calmodulin mRNAs found in rat tissue were present in PC12 cells. The relative abundance of the calmodulin mRNAs was 1.7 greater than 1.4 greater than 2.3 greater than 4.1 greater than 0.9 kb. NGF treatment caused a differential increase in these mRNAs. The 1.4 kb transcript (from Gene II) was increased earlier (at 1 day) and to a greater extent (3-fold) than any of the other mRNAs. Studies of the half-lives (t1/2) of these mRNAs suggested that the t1/2 varied with the mRNA; the smaller the mRNA, the shorter the t1/2. However, there were no significant effects of NGF on the t1/2 of any of the mRNAs. These studies indicate that NGF elevates calmodulin in PC12 cells by causing a differential increase in the multiple mRNAs for calmodulin and that the increase in calmodulin may play some part in NGF-induced neuronal differentiation in PC12 cells.

Animals↗
PubMed1991

Downregulation of stereotyped behavior and production of latent locomotor behaviors in mice treated continuously with quinpirole.

D1 and D2 dopamine receptors mediate different behavioral effects in animals. We have attempted to selectively modulate dopamine-mediated behaviors by continuously administering D2 agonists to mice. Acute administration of the D2 agonist quinpirole caused dose-related stereotyped effects; no locomotor or grooming behavior was apparent. Continuously infusing quinpirole with implanted Alzet minipumps initially produced stereotyped behavior, but this stereotypy decreased by 2 hours, and was completely absent from 3 hours to 6 days of infusion. Within 1 day after implanting quinpirole, there appeared a significant locomotor behavior that continued for the 6 days of infusion. Acute challenge doses of quinpirole given either 6 days after infusing quinpirole or 12 hours after removing the quinpirole implant failed to elicit any stereotyped behavior and did not alter the locomotor behavior. By contrast, acute challenge injections with the D1 agonist SKF 38393 administered 12 hours after removing the quinpirole implant produced a characteristic grooming response. In an attempt to learn the mechanism of the behavioral effects induced by the continuous administration of quinpirole, the actions of relatively selective D1 and D2 antagonists were examined. The D2 antagonist sulpiride inhibited the stereotypy but not the locomotion induced by quinpirole. By contrast, the D1 antagonist Sch 23390 blocked the locomotion but not the stereotypy induced by quinpirole. These results indicate that chronic administration of quinpirole causes two separate behavioral effects: (1) a downregulation of stereotypy, perhaps by downregulating D2 receptors; and (2) the development of locomotion, which appears to involve both the downregulation of D2 receptors and an activation of D1 dopaminergic mechanisms.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1979

Microwaves: effect on thermoregulatory behavior in rats.

Rats, with their fur clipped, pressed a lever to turn on an infrared lamp while in a cold chamber. When they were exposed to continuous-wave microwaves at 2450 megahertz for 15-minute periods, the rate at which they turned on the infrared lamp decreased as a function of the microwave power density, which ranged between 5 and 20 milliwatts per square centimeter. This result indicates that behaviorally significant levels of heating may occur at an exposure duration and intensities that do not produce measurable changes in many other behavioral measures or in colonic temperature. Further study of how microwaves affect thermoregulatory behavior may help us understand such phenomena as the reported "nonthermal" behavioral effects of microwaves.

Animals↗