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Biomedical subjects

K Mueller

Publications and source records attributed to K Mueller.

At least 55 records · Page 3Linked to original sources
PubMed1994

Stimulation of trabecular bone formation by insulin-like growth factor I in adult ovariectomized rats.

Although in vitro experiments indicate that insulin-like growth factor I (IGF-I) is an anabolic hormone in bone cell metabolism, the effects of IGF-I in vivo on bone formation are unclear. We thus investigated whether IGF-I is able to stimulate bone formation in adult rats with established osteopenia induced by ovariectomy (OVX). IGF-I was administered at daily doses of 0.05, 0.2, and 0.8 mg/kg for 3 wk. OVX induced a marked osteopenia in femur and tibia. Administration of IGF-I increased trabecular bone mass with a maximal effect at 0.2 mg/kg. The same dose stimulated bone formation, as revealed by an increase in osteoid surface, osteoblast surface, triple tetracycline-labeled surface, and bone formation rate. The mineral apposition rate was equally stimulated at all doses. At the highest dose, IGF-I increased osteoclast surface and osteoclast number. These data indicate that, in the adult OVX rat, IGF-I stimulates bone formation and increases trabecular bone volume at medium doses and enhances the histological indexes of bone resorption at high doses.

Alkaline Phosphatase↗
PubMed1994

Delivering services to the rural elderly: a study of policy implementation.

This article presents an analysis of two demonstration projects designed to improve delivery of services to elderly residents of rural Nebraska. One project employs a statewide system of care management focused on individual clients. In the other, local agencies in four communities coordinate services by using the local senior center as a focal point. This article uses established theory of policy implementation to illustrate problems encountered in starting new social programs that require state-local cooperation. Four guidelines are suggested for policymakers: (a) if local agencies are responsible for implementation, local managers must be involved in all the planning activities for new programs; (b) clear guidelines are needed to be sure that there is consensus concerning the details of implementation; (c) all health care providers should be involved in implementation when health care services are being coordinated; and (d) community coordinating councils can be effective.

Aged↗
PubMed1994

Effect of diallyl trisulfide on induction of UDS by mutagenic drugs in primary rat hepatocytes.

Most of anticancer drugs are mutagenic. A possible exception is diallyl trisulfide (DAT), a component of garlic. It is an antimutagenic anticancer chemical although it is mainly used as antibiotic. Its modifying effect on induction of UDS by mutagenic mitomycin C (MMC), cyclophosphamide (CP) and cis-diamine dichloroplatin (DDP) was investigated with the UDS assay in the primary cultures of Wistar rat hepatocytes (hpc) using the autoradiographic technique. Results showed that 1.0-4.0 nmol/ml of DAT did not induce UDS and that MMC, CP and DDP resulted in a significant induction of dose-dependent UDS. DAT enhanced induction of UDS by these drugs. A dose-effect relationship was observed between dose of DAT and enhancement of induction of UDS. However, the mechanism of the enhancement is not clear.

Allyl Compounds↗
PubMed1993

Mechanisms of upstream activation of the rrnD promoter P1 of Escherichia coli.

The rrn promoter regions of Escherichia coli contain a stretch of DNA, rich in An and Tn homopolymer sequences, which is located upstream of the tandem promoters P1 and P2. We have studied the effects of the upstream sequence of the rrnD operon on promoter function, using deletion variants for in vitro transcription. The presence of the upstream activating sequence (UAS) was found to increase P1 promoter strength without influencing P2. Two modes of P1 activation could be distinguished: a stimulation of P1 depending on the interaction of the factor of inversion stimulation (FIS) with the UAS (within the deletion boundaries of -50 and -112) and second, a factor-independent activation requiring the proximal part of the UAS (within the boundaries of -50 and -89). Both modes of activation were previously observed in the case of the rrnB operon and were ascribed to increased constants of RNA polymerase binding to P1 (Leirmo, S., and Gourse, R. L. (1991) J. Mol. Biol. 220, 555-568; Zacharias, M., Theissen, G., Bradaczek, C., and Wagner, R. (1991) Biochimie 73, 699-712). Our results show, however, that the mechanisms of upstream activation may vary with the reaction conditions. In a complex transcription system, originally designed for the use of cell extracts, FIS enhances first-order reactions that convert binary (open) complexes to transcribing complexes. Initiated complexes are stabilized by FIS. The factor-independent mode of P1 activation involves influences of the UAS on complex isomerizations as well as on binary complex formation. The results show that low molecular weight components of the complex transcription system change the function of the RNA polymerase at the rrn promoters (not at the reference promoter Ptac), so that the conversion of open to transcribing P1-complexes becomes dependent on the UAS and FIS.

Base Sequence↗
PubMed1993

Locomotor stereotypy is produced by methylphenidate and amfonelic acid and reduced by haloperidol but not clozapine or thioridazine.

In addition to its well-known behavioral effects in rats, amphetamine also produces patterned locomotion (referred to below as locomotor stereotypy) in an open field. Locomotor stereotypy may be mediated by different mechanisms than those mediating the better-known behavioral effects of amphetamine. To determine whether the ability to produce locomotor stereotypy is an exclusive property of amphetamine or is a property of many amphetamine-like stimulants, several doses of methylphenidate and amfonelic acid were tested. The ability of both atypical and typical neuroleptics to block amphetamine-induced locomotor stereotypy was also tested. Both amfonelic acid and methylphenidate produced some degree of locomotor stereotypy. In addition, amphetamine-induced locomotor stereotypy was reduced by haloperidol but not by clozapine or thioridazine. These data suggest that locomotor stereotypy is more closely related to focused stereotypy than to hyperlocomotion.

Animals↗
PubMed1992

Correlates of health insurance coverage: evidence from the Midwest.

The Midwest is often overlooked in national studies of health insurance status. We analyzed the economic and social characteristics of uninsured and underinsured individuals and households in a Midwestern state using both bivariate and multivariate techniques. As in much of the country, economic factors, particularly income and employment, were most significant in accounting for insurance coverage. Unexpectedly, rural and urban residents were equally likely to lack insurance. Results indicate that in rural areas, underinsurance may be a greater problem than uninsurance, and that income-based health insurance is more effective than employer-provided plans in reaching all Americans.

Adolescent↗
PubMed1991

Functional characteristics of the rrnD promoters of Escherichia coli.

The function of the tandem rrnD promoters (P1, P2) of Escherichia coli, which are highly efficient in directing rRNA synthesis, was studied in vitro using the strong hybrid promoter PtacI as a reference. One of the characteristics of the rrnD promoters is a pronounced instability of binary and initiating complexes formed with RNA polymerase. The rate of productive complex formation and of chain initiation at these promoters was found to be limited by a step in binary complex transitions with an apparent first-order rate constant equal to 3.9 x 10(-2) s-1. A comparison of this rate with that determined previously by filter binding assays (Gourse, R. (1988) Nucleic Acids Res. 16, 9789-9809) suggests that the rate-limiting step is a conversion of an intermediate species of open complex to one that is efficient in productive initiation. The slow rate of this reaction and the instability of open complexes account for the relatively low competitive strengths of the rrnD promoters. However, this limitation of rrn promoter function changes with promoter occupancy because the rate of chain initiation increased after completion of the first round of initiation. Despite their poor competitive strength, the rrnD promoters are more productive than PtacI at nonlimiting RNA polymerase concentrations. This can be ascribed to the different rates with which RNA polymerases leave PtacI and the rrnD promoters. These functional differences of the promoters are consistent with a "stressed intermediate" model of chain initiation (Straney, D.C., and Crothers, D.M. (1987) J. Mol. Biol. 193, 267-278) which predicts that rapid clearance of the rrn promoters is mechanistically related to the instability of the binary complexes.

Chromosome Deletion↗
PubMed1991

Effect of acupuncture-point stimulation on diastolic blood pressure in hypertensive subjects: a preliminary study.

Electrical stimulation of four specific acupuncture points (Liver 3, Stomach 36, Large Intestine 11, and the Groove for Lowering Blood Pressure) was examined in order to determine the effect of this stimulation on diastolic blood pressure in 10 subjects with diastolic hypertension. Subjects were randomly divided into two groups: (1) an Acu-ES group, which received electrical stimulation applied to the four antihypertensive acupuncture points, and (2) a Sham-ES group, which received electrical stimulation applied to non-acupuncture-point areas. A repeated-measures analysis of variance revealed a significant, immediate poststimulation reduction of diastolic blood pressure for the Acu-Es group versus the Sham-ES group. Further studies are needed to determine whether there are other acupuncture points, stimulation characteristics, or modalities that can enhance this treatment effect and whether the treatment effect can last for a clinically significant period of time.

Acupuncture Points↗
PubMed1990

Enkephalin prevents CCK-induced enhancement of amphetamine-induced locomotor stereotypy.

Enkephalin (ENK) and/or cholecystokinin octapeptide (CCK-8) were infused into nucleus accumbens of rats prior to injection with saline or 1.0 mg/kg amphetamine. Behavior was observed in an open-field paradigm which allowed assessment of locomotor stereotypy (repetitive routes or patterns of locomotion) as well as assessment of lines crossed and rears. Neither CCK nor ENK nor the combination of the two affected the behavior of saline-injected rats in the open field. CCK enhanced the locomotor stereotypy produced by amphetamine without affecting any of the other behaviors recorded. ENK had no effect on the behavior of amphetamine-treated rats when given alone, but ENK prevented the effect of CCK. Thus, enkephalin and CCK interact to modulate amphetamine-induced locomotor stereotypy.

Amphetamines↗
PubMed1990

The effects of haloperidol and amphetamine on ascorbic acid and uric acid in caudate and nucleus accumbens of rats as measured by voltammetry in vivo.

The ability of haloperidol (0.1 mg/kg) to reduce the amphetamine-induced (2 and 5 mg/kg) increase in ascorbic and uric acid in anterior caudate and in nucleus accumbens was tested using voltammetry in vivo. In both areas, haloperidol reduced the amphetamine-induced increase in uric acid. In both areas, haloperidol only marginally affected the amphetamine-induced increase in ascorbic acid. Amphetamine-induced increases in uric acid were more nearly dose-related than changes in ascorbic acid. Of the two compounds, uric acid seems more likely to be associated with dopamine.

Amphetamine↗
PubMed1990

Scopolamine produces locomotor stereotypy in an open field but apomorphine does not.

Both dopaminergic and nondopaminergic drugs produce hyperlocomotion in rats. Dopaminergic drugs also produce focused stereotypy (absence of locomotion and intense sniffing or licking/biting of a restricted area of the environment). Some drugs produce repetitive routes of locomotion; this phenomenon might represent a combination of hyperlocomotion and stereotypy. Scopolamine (an acetylcholine antagonist) and apomorphine (a dopamine agonist) both produce hyperlocomotion in rats; apomorphine also produces focused stereotypy but scopolamine does not. This research determines whether these drugs also produce locomotor stereotypy as measured by gamma. Scopolamine (0.5 and 2.0 mg/kg) produced locomotor stereotypy at both doses. Apomorphine (1.0, 2.0, and 3.0 mg/kg) failed to reliably produce locomotor stereotypy. Thus, there is not necessarily a relationship between the ability of a drug to produce focused stereotypy and the ability of the drug to produce locomotor stereotypy.

Animals↗
PubMed1990

The effects of amphetamine and pilocarpine on the release of ascorbic and uric acid in several rat brain areas.

Linear sweep voltammetry was used to investigate the effects of amphetamine (which enhances the release of dopamine) and/or pilocarpine (a cholinergic agonist) on the release of ascorbic acid and uric acid in brain areas differing in dopamine and acetylcholine concentrations. In caudate, nucleus accumbens, and hippocampus, the magnitude of the amphetamine-induced increase in ascorbic acid was roughly correlated with dopamine content of the brain area tested. Cingulate cortex was a notable exception; the increase in ascorbic acid was greater than that in nucleus accumbens. Pilocarpine produced the greatest increase in ascorbic acid in cingulate cortex, even though cingulate cortex has the lowest acetylcholine concentration of the brain areas tested. Except for cingulate cortex, the ascorbic acid data were consistent with the hypothesis that amphetamine and pilocarpine release different pools of ascorbic acid. The uric acid data were consistent with the hypothesis that amphetamine and pilocarpine release the same pool of uric acid. The unexpected findings in cingulate cortex may point to an important role of ascorbic acid in this brain area.

Amphetamine↗
PubMed1990

Hypolipidemic activity of rifamycin derivatives.

Series of 3-piperidinyl- and 3-piperazinylrifamycins and to a certain extent 3-hydrazonorifamycins all bearing lipophilic side chains were found to exert potent hypolipidemic activity in lowering both serum cholesterol and LDL-cholesterol in rats. Starting from 3-[N'-(2,4,6-trimethylbenzyl)-N-piperazinyl]rifamycin SV (compound 25), a series of derivatives were synthesized with the aim of dissociating the hypolipidemic from the antibacterial activity, leading to the 8-O,N-dipivaloyl derivative of 25 (compound 48), which is devoid of any antibacterial activity but shows about 50-60% reduction of LDL-cholesterol and 20-30% reduction of serum cholesterol at a dose of 10 mg/kg. Compound 48 was selected for further pharmacological evaluation.

Animals↗
PubMed1989

Repeated administration of high doses of amphetamine increases release of ascorbic acid in caudate but not nucleus accumbens.

Linear sweep voltammetry with carbon paste electrodes was used to monitor extracellular ascorbic acid (AA) in the caudate nucleus and nucleus accumbens of behaving rats. Amphetamine (2 or 5 mg/kg) was administered 4, 6 and 8 days after surgery. In general the amphetamine-induced increase in AA was greater in the caudate than in the nucleus accumbens. Furthermore, in the nucleus accumbens the amphetamine-induced increase in AA was very similar on all test days, but in the caudate the increase in AA produced by 5 mg/kg amphetamine was progressively larger on each test day. Thus AA seems to be regulated differently in the caudate and nucleus accumbens.

Amphetamines↗
PubMed1989

Triazolam attenuates amphetamine but not morphine conditioned place preferences.

In a series of four experiments the benzodiazepine triazolam was tested for reinforcing effects and for effects on reinforcement induced by amphetamine and morphine. Reinforcement was assessed in a conditioned place preference paradigm. Triazolam did not produce reinforcing or aversive effects when administered in doses ranging from 0.0625 to 0.5 mg/kg. Triazolam did attenuate reinforcing effects produced by 0.75 and 1.25 mg/kg amphetamine. No effect of triazolam was observed on morphine-induced reinforcement. These results indicate that the administration of triazolam can affect the brain mechanisms that mediate the reinforcing effects of amphetamine but not morphine.

Amphetamine↗
PubMed1989

Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy.

Rat open field behavior is often used as a tool to study the behavioral effects of drugs. In this report, drug-induced patterns of locomotion in an open field were studied with the aid of a simple new statistic. Briefly, the animal's path through the open field is converted into a series of trips. Gamma (gamma) estimates the probability that the animal will repeat the trip that it has just exhibited; thus gamma quantifies "locomotor stereotypy". Trip lengths can also be compared across drug groups. Thus caffeine has no effect on gamma even though it produces a dose-related increase in locomotions. Caffeine does not produce amphetamine-like stereotypy. On the other hand, amphetamine produces a dose-related increase in gamma. Although gamma was designed to detect any pattern of locomotor behavior, rats treated with high doses of amphetamine almost always exhibited the same pattern of locomotor behavior - repetitive trips around the perimeter of the open field. Although further characterization of the statistic is necessary, these findings suggest that gamma has potential for quantifying "locomotor stereotypy" and for providing a more subtle description of locomotor behavior in general.

Amphetamine↗
PubMed1989

Infusions of cholecystokinin octapeptide into the ventral tegmental area potentiate amphetamine conditioned place preferences.

Cholecystokinin (CCK) and dopamine (DA) coexist in both cell body and terminal areas of a mesolimbic pathway that projects from the ventral tegmental area (VTA) to the nucleus accumbens (N ACC). Autoradiography reveals extensive CCK binding sites in the N ACC, but not in the VTA. However, iontophoresis of CCK into the VTA results in activation or deactivation of DA neuronal firing rates, and bursting activity (depending on the dose of CCK administered). CCK could have neuromodulatory effects on mesolimbic DA neurons. In two studies, behavioral effects of infusions of CCK into the VTA were examined in the conditioned place preference (CPP) paradigm. The CPP paradigm is a behavioral test used to assess reinforcement induced by drug administration. Drugs with reinforcing properties can condition preferences for novel environments. CCK infusions into VTA (0.0, 0.04, 0.4, and 4.0 ng/cannula) potentiated amphetamine CPPs in a dose-dependent linear manner. CCK infusions by themselves did not have significant effects in the CPP paradigm. Results indicate a neuromodulatory role for CCK on the neuronal mechanisms that mediate the reinforcing effects of amphetamine. Results also implicate sites of action for CCK in the VTA.

Amphetamine↗