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Biomedical subjects

W R Klemm

Publications and source records attributed to W R Klemm.

At least 19 recordsLinked to original sources
PubMed2001

Behavioral arrest: in search of the neural control system.

Scientists have spent hundreds of years trying to understand how the brain controls movement. Why has there been so little interest in knowing how the brain STOPS movement? This review calls attention to behavioral phenomena in which an animal or human undergoes temporary total-body arrest of movement, that is, behavioral arrest (BA). These states can be actively induced by visual stimuli, by body and limb manipulations, and by drugs. Historically, these states have been considered as unrelated, and their literature does not cross-connect. What is known about the causal mechanisms is scant, limited mostly to implication of the brainstem in manipulation-induced BA and dopaminergic blockade in the striatum in the case of drug-induced BA. The possibility has not been experimentally tested that all of these states share with each other not only an active global immobility in which awkward postures are maintained, but also underlying neural mechanisms. This review identifies key brainstem, diencephalic, and basal forebrain areas that seem to be involved in causing BA. We review the evidence that suggest a possible role in BA for the following brain structures: entopeduncular nucleus, medullary and pontine reticular zones, parabrachial region, pedunculopontine nucleus and nearby areas, substantia nigra, subthalamic nucleus, ventromedial thalamic nucleus, and zona incerta. Such areas may operate as a BA control system. Confirmation of which brain areas operate collectively in BA would require testing of several kinds of BA in the same animals with the same kinds of experimental tests. Areas and mechanisms might be elucidated through a strategic combination of the following research approaches: imaging (fMRI, c-fos), lesions (of areas, of afferent and efferent pathways), chemical microstimulation, and electrical recording (of multiple units and field potentials, with an emphasis on testing coherence among areas). We suggest the working hypothesis that BA is created and sustained by coherent, perhaps oscillatory, activity among a group of basal forebrain and brainstem areas that collectively disrupt the normal spinal and supraspinal sequencing controls of reciprocal actions on the extensors and flexors that otherwise produce movement.

Animals↗
PubMed2000

Coherent EEG indicators of cognitive binding during ambiguous figure tasks.

We tested the hypothesis that perception of an alternative image in ambiguous figures would be manifest as high-frequency (gamma) components that become synchronized over multiple scalp sites as a "cognitive binding" process occurs. For 171 combinations of data from 19 electrodes, obtained from 17 subjects and 10 replicate stimuli, we calculated the difference in correlation between the response to first seeing an ambiguous figure and when the alternative percept for that figure became consciously realized (cognitively bound). Numerous statistically significant correlation differences occurred in all frequency bands tested with ambiguous-figure stimulation, but not in two kinds of control data (a reaction-time test to sound stimuli and a no-task, mind-wandering test). Statistically significant correlation changes were widespread, involving frontal, parietal, central, and occipital regions of both hemispheres. Correlation changes were evident at each of five frequency bands, ranging up to 62.5 Hz. Most of the statistically significant correlation changes were not between adjacent sites but between sites relatively distant, both ipsilateral and contralateral. Typically, these correlation changes occurred in more than one frequency band. These results suggest that cognitive binding is a distinct mental state that is reliably induced by ambiguous-figure perception tasks. Coherent oscillations at multiple frequencies may reflect the mechanism by which such binding occurs. Moreover, different coherent frequencies may mediate different components of the total cognitive-binding process.

Adult↗
PubMed1998

Biological water and its role in the effects of alcohol.

Alcohol and water compete with each other on target membrane molecules, specifically, lipids and proteins near the membrane surface. The basis for this competition is the hydrogen bonding capability of both compounds. But alcohol's amphiphilic properties give it the capability to be attracted simultaneously to both hydrophobic and hydrophilic targets. Thus, alcohol could bind certain targets preferentially and displace water, leading to conformational consequences. This article reviews the clustering and organized character of biological water, which modulates the conformation of membrane surface molecules, particularly receptor protein. Any alcohol-induced displacement of biological water on or inside of membrane proteins creates the opportunity for allosteric change in membrane receptors. This interaction may also prevail in organelles, such as the Golgi apparatus, which have relatively low concentrations of bulk water. Target molecules of particular interest in neuronal membrane are zwitteronic phospholipids, gangliosides, and membrane proteins, including glycoproteins. FTIR and NMR spectroscopic evidence from model membrane systems shows that alcohol has a nonstereospecific binding capability for membrane surface molecules and that such binding occurs at sites that are otherwise occupied by hydrogen-bonded water. The significance of these effects seems to lie in the need to learn more about biological water as an active participant in biochemical actions. Proposed herein is a new working hypothesis that the molecular targets of ethanol action most deserving of study are those where water is trapped and there is little bulk water. Proteins (enzymes and receptors) certainly differ in this regard, as do organelles.

Animals↗
PubMed1997

Variations of equine urinary volatile compounds during the oestrous cycle.

Equine urine was analysed by capillary gas chromatography. The volatile profiles from oestrous and dioestrous samples were compared to establish any qualitative or quantitative difference that may have potential value in olfactory communication. Forty-five different volatile compounds were detected. Of these, 17 major compounds were common to all chromatograms. The chemical profile of oestrous urine was distinguished by the presence of a unique peak that was not present in dioestrous samples. Numerous constituents exhibited endocrine dependence: while the concentrations of seix peaks increased at oestrus, the concentrations of another five peaks decreased at the same time. Since oestrous urine, but not dioestrous urine, has been shown to elicit sexual behaviour in the stallion, the unique peak, together with the peaks that were present in increased concentration at oestrus, may represent important chemical signals that stallions use to detect urinary 'oestrous odours'. Statistical analyses also indicated that the relative ratios (normalized peak areas) of many peaks changed significantly across the oestrous cycle: the rations increased in nine peaks, decreased in six peaks, and remained constant in two peaks at oestrus.

Analysis of Variance↗
PubMed1997

Volatile compounds of bovine milk as related to the stage of the estrous cycle.

Previous reports on behavioral assays with trained dogs suggested that milk samples from cows at diestrus, proestrus, and estrus had different odors. To identify the odor differences, volatile compounds in milk were isolated and analyzed by gas chromatography and mass spectrometry. About 80 peaks were detected in each chromatogram, of which 59 were present in all samples, and 23 were tentatively identified. The major identified compounds included the following six structurally distinct classes: ester, aldehyde, ketone, alcohol, fatty acid, and lactone. Although no unique peaks were found to be specific to samples taken at diestrus, proestrus, or estrus, 36 compounds exhibited significant differences in concentration among the three reproductive stages. These quantitative differences may account for the variation of milk odors during the estrous cycle. In order to investigate the quantitative differences systematically, multivariate discriminant techniques were used to relate the gas chromatographic profiles with the three stages of the estrous cycle. Stepwise discriminant analysis indicated that 15 of the 59 peaks in each chromatogram could best be used to reveal the differences among milk samples taken at diestrus, proestrus, and estrus stages. The discriminant function based on the 15 key peaks could classify all of the samples into their original categories at a total accuracy of 97.9%. Canonical analysis indicated that milk samples from different stages were clearly separated from each other in a two-dimensional space.

Alcohols↗
PubMed1993

A possible feline model for human blepharospasm.

'Benign essential blepharospasm' is a human eyelid disorder of unknown aetiology characterized by involuntary, bilateral, and disabling spasmodic contracture of the orbicularis oculi muscle. Treatments are frequently disappointing. Here we report what might be a first step toward developing an animal model for exploring mechanisms of the disorder and potential treatments. We surgically implanted stimulating electrodes into brain areas known to supply input to the lateral division of the facial nerve nucleus to induce blinking by electrical stimulation. Single-pulse stimuli at or near the facial, parabrachial, red, and interstitial nuclei produced consistent stimulus-induced eyelid contractions. Responses were ipsilateral to stimulation, except for the interstitial nucleus where contralateral responses occurred. Little or no other movements of the face, head, or body occurred at eye-blink threshold voltages. When these sites were stimulated with pulse trains, eyelid closures followed stimulus frequency and tended to fuse into constant closure. Thresholds at each stimulus site remained constant during three days of testing. Drug treatments produced no consistent effect on eye-blink threshold from any stimulation site, even when general behaviour was affected. We conclude that these input pathways to the facial nucleus may contribute to blepharospasm and that future neurochemical and electrophysiological study of these pathways may produce a suitable animal model for understanding this disorder.

Animals↗
PubMed1992

Innervation of the feline eyelids.

The innervation of the eyelids is incompletely understood. This is a particular problem for those who wish to develop animal models of eyelid dysfunction in humans. Blepharospasm, for example, is a disease of uncontrolled eyelid spasm that is difficult to manage clinically because the aetiology is not understood. The anatomical literature on eyelid innervation is sparse and even conflicting. We attempted to study eyelid innervation, both sensory and motor, with injection of horseradish peroxidase (HRP) into the superior eyelid, inferior eyelid, and bulbar conjunctiva. We used 13 anesthetized weanling cats. Shape and structure of the facial nucleus varied along its rostrocaudal extent, but there was a clear demarcation of lateral and medial division. HRP-filled facial nucleus cells were ipsilateral to the injection site, and label appeared throughout the rostrocaudal length. All injection sites, including bulbar conjunctiva, labelled facial nucleus neurons located with overlapping distribution, predominantly in the dorsal part of the lateral division. Likewise, heavy labelling occurred throughout the entire ipsilateral cranial cervical ganglion and the trigeminal ganglion in all kittens. Injection of upper or lower eyelids caused some labelling in the second through the fourth cervical spinal ganglia.

Animals↗
PubMed1992

FTIR evidence for alcohol binding and dehydration in phospholipid and ganglioside micelles.

We theorize that intoxicants and modern anesthetics bind at the membrane-water interface and displace (dehydrate) bound water molecules by breaking the hydrogen bonds. We tested this hypothesis by examining the effect of butanol on the binding of water to the polar regions of lipids in reversed micelles. Understanding the mechanisms of intoxication requires studies in physiologically relevant systems such as systems containing sialoglycoconjugates, especially gangliosides, which concentrate in the synapses of neural tissue. Therefore, we compared butanol effects on phospholipid with effects on ganglioside. Hydrogen-bond breaking activity of 1-butanol was studied in reversed micelles made of dipalmitoylphosphotidylcholine (DPPC), ganglioside (GM1 and GT1b) or the lipid mixture in a D2O-CCl4 medium. Fourier transform infrared spectroscopy (FTIR) data indicated that 1-butanol binds to DPPC and to gangliosides. Adding GM1 to the DPPC micelles introduces a new binding site for the alcohol. GT1b binds more butanol than GM1, because of more binding sites provided by extra sialic acid moieties. Spectral red shifts indicate that both water and butanol bind to the C = O group of sialic acid. Butanol partially releases the surface-bound water by disrupting hydrogen bonds, as indicated by an appearance of a sharp new free OD stretching band of the released D2O molecules. However, control studies with lipid-free systems in CCl4 revealed that a free OD peak could occur from a deuterium exchange reaction between D2O and 1-butanol(ol-h).(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Are there EEG correlates of mental states in animals?

The thesis of this paper emerges from the fact that mental states are generated by neural processes that also produce an associated electroencephalogram (EEG). Thus, it is logical to expect correlations between mental state and EEG. The corollary is that the EEG can serve as an index of mental state, which can be particularly useful for studies in animals, where mental states are much less accessible for objective study than in humans. Herein, I briefly review the traditional approaches that have informed our attitudes about animal mental states. Virtually all of our conclusions about mental states in animals are drawn by inference from behavioral observation, a process that is highly and unavoidably subject to anthropomorphism. Traditionally, the electroencephalogram (EEG) has been used in a crude way as an objective indication of physical and behavioral state in animals. This, however, has led to substantial controversy, because there are several situations in which EEG patterns and behavior seem to be dissociated. We not only fail to understand these dissociated states, but there are also important humane animal-welfare issues that remain unresolved because we do not fully understand the extent to which the EEG can reflect mental state. At issue is whether EEG-behavioral dissociations, to the extent that they exist, are proof that the EEG is dissociated from mental states. Powerful new EEG methods, such as topographical EEG mapping, wavelet analysis, and testing for nonlinear ('chaotic') dynamical properties and short-term serial dependencies, are now available for studying the extent to which the EEG can index thinking and feeling in humans and, by extrapolation, in animals. Critics who have become disenchanted with the utility of the EEG should at least concede that fresh approaches to old problems are now available and should therefore be thoughtfully considered. If such research does nothing more than improve the rigor of the debate over animal welfare and rights issues, it will be worth the effort.

Animals↗
PubMed1991

Ganglioside or sialic acid attenuates ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature.

1. This laboratory has previously reported that pretreatment with ganglioside, or even with its constituent, sialic acid (SA), can attenuate certain intoxicating effects of ethanol. It was important to see if these findings could be replicated, particularly by using other measures of ethanol effects. Herein we report that pretreatment with either gangliosides or SA attenuated ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature. 2. An ethanol dose of 4 gm/kg caused a temperature drop of about 3 degrees C, which was unaffected by any pretreatment. The onset to sleep, however, was delayed an average of 18 or 36 secs in mice pretreated with ganglioside or SA, respectively. Ethanol-only (4 gm/kg) depressed mean cumulative locomotor activity to 31% of normal, whereas the depression was 83% of normal with beef brain ganglioside pretreatment. At 2 gm/kg ethanol alone decreased nose poking in a hole-board test to 29% of normal, but the depression was only 55-63% of normal with SA or ganglioside pretreatment. In a staircase climbing anxiety test, this dose of ethanol had no effect by itself, but both ganglioside and SA pre-treatment increased climbing by 22%. Ethanol did depress rearing to only 11% of normal, whereas rearing was 51 and 99% of normal with SA and ganglioside pretreatment, respectively. In a dark-preference test, ethanol-only caused mice to spend 64% of the time in the light, compared to 31% for controls. Time in the light was only 39 and 46% with ganglioside and SA pretreatment, respectively. 3. Blood levels of ethanol were not significantly affected by pretreatment. 4. When given alone, gangliosides significantly stimulated locomotion and staircase climbing. SA significantly decreased rearing in the staircase test. Both gangliosides and SA tended to increase nose poking, number of crossings in the dark-preference test, and time in a lighted compartment. Thus, it is possible that some of the attenuation of intoxication is attributable to non-specific stimulant properties of gangliosides and SA.

Animals↗
PubMed1990

Effect of acute injections of ethanol on lipid and protein-bound sialic acid in mice of different ages.

Mice of different age groups (weanling, young adult and aged) were tested for changes in brain lipid- and protein-bound sialic acid (SA) 2 h after ethanol (2 g/kg, i.p.), either as a single dose or after binge dosing of five repeated doses of ethanol spaced 2 h apart. The results clarify our earlier demonstrations that acute ethanol can reduce whole brain SA. Ethanol generally decreased SA of both gangliosidic and glycoprotein origin, with the effect varying with number of doses and mouse age. Single-dose ethanol decreased both lipid-bound and protein-bound SA in young adults and decreased lipid-bound SA in aged mice. There was no effect on lipid-bound SA in weanlings, but weanlings did have a 72% decline in protein-bound SA. Repeated injections in young adults did not cause the SA decrease seen with acute injection. In both weanling and aged mice, however, repeated injections did cause large decreases in both lipid- and protein-bound SA. Small, but statistically significant, changes also occurred in free SA. Ethanol increased free SA in singly-dosed young adults and in multiply-dosed aged adults, while causing a distinct decrease in singly-dosed weanlings.

Age Factors↗
PubMed1989

Differences in susceptibility of rat liver and brain sialidases to ethanol and gangliosides.

Based on reports that ethanol can decrease the level of sialic acid (SA) (neuraminic acid) in several tissues, we tested the hypothesis that ethanol promotes SA cleavage by enhancing the activity of sialidases (neuraminidases). We also investigated whether brain and liver sialidases have the same response to ethanol and gangliosides, especially since our prior studies have demonstrated that gangliosides could antagonize ethanol-induced behavior. Experiments were conducted on homogenates of brain and liver and of liver slices of adult rats. In liver slices, cleavage of SA did not fall in proportion to the ethanol-induced inhibition of sialidase; in fact, at 0.1 M ethanol, free SA increased, even though sialidase was inhibited. Brain sialidase activity on endogenous sialoglycoconjugates was much more resistant to ethanol than liver sialidase and was fully active even in concentrations as high as 1 M. When gangliosides were incubated with liver slices in the absence of ethanol, sialidase was markedly stimulated. The ethanol-induced inhibition of sialdase in liver slices was mimicked by sorbitol, suggesting that the inhibition may be caused by a shift in redox state as a result of increased NADH. The ethanol metabolite, acetaldehyde, does not seem to be a factor, because sialidase inhibition still occurred when slices were incubated with ethanol containing pyrazole. The results indicate that ethanol promotes the accumulation of free SA in liver without stimulating sialdase; our other work suggests that the cause is an increase in accessibility to sialoglycoconjugates rather than decreased utilization of SA. Brain and liver sialidases clearly respond differently to both ethanol and gangliosides.

Animals↗
PubMed1989

Drug effects on active immobility responses: what they tell us about neurotransmitter systems and motor functions.

The literature reviewed indicates that active immobility can be promoted by systemic injections of various neurotransmitter systems, as follows: (1) Dopaminergic blockade of both D1 and D2 receptor subtypes. (2) Cholinergic agonism of both muscarinic and nicotinic receptors. (3) Noradrenergic agonism of both alpha-1 and alpha-2 receptors (but these agonists may interfere with haloperidol- and reserpine-induced catalepsy). (4) GABA agonism. (5) Histamine agonism, particularly at the H1 receptor. (6) Opiate agonism, including action of many endogenous opiate peptides, particularly those affecting mu and delta receptors. (7) Agonism by certain other peptides (neurotensin, cholecystokinin). Among the major interactions of neurotransmitter systems that regulate immobility, are the following: (1) Cholinergic-dopaminergic (cholinolytics disrupt catalepsy of dopaminergic blockade and dopaminergic agonists tend to disrupt cholinomimetic catalepsy). (2) Opiate-induced catalepsy is antagonized by the dopamine agonist, apomorphine, but is enhanced by amphetamine. It is also antagonized by certain alpha-2 adrenergic agonists, while it does not seem to be antagonized by anticholinergics. (3) Numerous other interactions have been reported, involving opiates and MSH, serotonin and dopamine mimetics, serotonin and ketamine, GABA and neuroleptics, neurotensin and anticholinergics and histamine. The significance of the multiple neurotransmitter systems is unknown. One possible explanation is that the various neurotransmitter systems participate in mediating the sensory inputs that are involved in triggering immobility and regulate the higher-order limbic and basal ganglia processing reactions that engage a final motor output pathway from the brainstem. The brain is assumed to contain two sets of systems, each with its own, or possibly overlapping, set of neurotransmitter systems, that promote either active immobility or locomotion. The systems reciprocally inhibit each other. Another view, not mutually exclusive, is that output from the locomotor-promoting system provides a negative feedback, via the active immobility pathways, to act as a "brake" on movement, while at the same time maintaining the muscular tonus that is characteristic of active immobility.

Animals↗
PubMed1989

Ethanol-induced hydrolysis of brain sialoglycoconjugates in the rat: effect of sialic acid in antagonizing ethanol intoxication.

Several reports indicate that acute ethanol promotes the cleavage of brain sialoglycoconjugates (SGC). We attempted to confirm this effect by monitoring cleavage of sialic acid (SA) that had been radiolabeled by pretreatment with the specific precursor of SA, N-[3H]acetyl-D-mannosamine, injected intracerebroventricularly into rats 20 h prior to ethanol injection (2 or 3 g/kg, given four times in a simulated "binge drinking" protocol). Analysis of the residual labeled material revealed a significant reduction of radiolabel (p less than 0.01), as compared to saline controls. A dose of 3 g/kg diminished the total labeled SGC by half. Brain sialidase activity was not affected by the ethanol treatment. Since ethanol intoxication is associated with enhanced SA cleavage, one hypothesis needing testing is that loss of SA might help to cause intoxication. If so, pretreatment with SA might antagonize intoxication, presumably by offsetting loss due to cleavage of SA. Consistent with our earlier results, we found that when sialic acid was given i.p. (25 mg/kg), 1, 6, or 24 h prior to ethanol injection (4 g/kg, i.p.), the sleep time was reduced by 35-40% and the performance on rotorod was significantly enhanced (p less than 0.01). When ethanol was replaced by pentobarbital (40 mg/kg), the sleep time was increased (approximately 30%) at 6 h after injection with either 25 or 100 mg/kg sialic acid, whereas at the 24 h postinjection it was decreased (approximately 20%) at both doses. The results suggest that sialic acid is a key component in mediating ethanol effects and perhaps also, in a different way, anesthetic effects.

Alcoholic Intoxication↗
PubMed1988

Gangliosides, or sialic acid, antagonize ethanol intoxication.

Because ethanol elicits a dose-dependent hydrolysis of brain sialogangliosides, we tested the possibility that injected gangliosides might antagonize intoxicating doses of ethanol. Clear anti-intoxication effects were seen at 24 hr post-injection of mixed mouse-brain gangliosides at 125-130 mg/kg, but not at lower or higher doses. Sleep time was reduced on the order of 50%, and roto-rod agility was significantly enhanced. Sialic acid (SA) similarly antagonized ethanol; however, the precursor of SA, N-acetyl-D-mannosamine, as well as ceramide and asialoganglioside did not.

Alcohol Deterrents↗
PubMed1988

D-1 and D-2 receptor blockade have additive cataleptic effects in mice, but receptor effects may interact in opposite ways.

The dopaminergic role of D-1 and D-2 receptors in catalepsy was evaluated using drugs with preferential receptor affinities. The D-1 antagonist, SCH 23390, caused distinct catalepsy in mice at 1, 2, and 10 mg/kg, IP, but not at two lower doses. The selective D-1 blocker, molindone, also caused catalepsy at 5 and 10 mg/kg; and blockade of both receptor types produced additive cataleptogenic effects. Apomorphine (4 mg/kg), which is an agonist for both receptors, potentiated SCH 23390-induced catalepsy much more than it did the catalepsy induced by molindone; the potentiation was produced by higher, not lower, doses of apomorphine. To determine if the apomorphine potentiation was mediated by D-1 or D-2 receptors, we tested selective agonists in mice that were concurrently injected with selective blockers. SCH 23390-induced catalepsy was potentiated by a large dose of the D-2 agonist, bromocriptine. The catalepsy of D-2 blockade with molindone was not potentiated by the D-1 agonist, SKF 38393, which slightly disrupted the catalepsy of D-2 blockade. We conclude that catalepsy is not a simple D-2 blockade phenomenon and that preferential antagonism of either receptor type can cause catalepsy. Catalepsy is most profound when both receptor types are blocked. Dopamine agonists, in large concentrations, are known to promote movements, and thus it is not surprising that they tend to disrupt catalepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

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