Biomedical subjects

M Gabriel

Publications and source records attributed to M Gabriel.

At least 37 records · Page 2Linked to original sources

PubMed1996

The Current State of Solar Modeling

Data from the Global Oscillation Network Group (GONG) project and other helioseismic experiments provide a test for models of stellar interiors and for the thermodynamic and radiative properties, on which the models depend, of matter under the extreme conditions found in the sun. Current models are in agreement with the helioseismic inferences, which suggests, for example, that the disagreement between the predicted and observed fluxes of neutrinos from the sun is not caused by errors in the models. However, the GONG data reveal subtle errors in the models, such as an excess in sound speed just beneath the convection zone. These discrepancies indicate effects that have so far not been correctly accounted for; for example, it is plausible that the sound-speed differences reflect weak mixing in stellar interiors, of potential importance to the overall evolution of stars and ultimately to estimates of the age of the galaxy based on stellar evolution calculations.

Journal Article↗

PubMed1996

Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior.

Neuronal discharges related to acoustic conditional stimuli and locomotive behavioral responses of 152 anterior and medial dorsal (MD) thalamic and cingulate cortical single-units sorted from multi-unit activity were recorded as rabbits performed in a discriminative avoidance task. The goals were: (1) to document the single-unit constituents of multi-site, multi-unit activity recorded previously in response to the conditional stimuli used for avoidance training; and (2) to document neuronal activity related to the onset of the behavioral avoidance response. Ninety-five units showed discriminative discharges: significantly different firing rates 90-700 ms after a foot shock-predictive conditional stimulus (CS+) than to a safety-predictive conditional stimulus (CS-). In accord with the multi-unit data, a majority of these units discharged at higher rates after the CS+ than after the CS-. The discharge rates of 87 units were greater during the 2-s period preceding the onset of avoidance responses than during comparable trial periods after CS-presentations followed by no response. Fifty-six of the 87 avoidance-related units exhibited a progressive ramp-like firing increase 2 s before the avoidance response, with the maximal discharge rate occurring 200 ms before the response. These dynamic pre-avoidance discharges occurred first in limbic thalamus then in cingulate cortex, suggesting that cortical pre-motor processing may confer temporal specificity upon a more generalized command volley relayed from thalamus. Unlike the multi-unit data, 24 neurons exhibited inverse discrimination, i.e., significantly greater discharges in response to the CS-than to the CS+. Also 27 neurons showed significantly more firing in the 2-s period before the end of CS-trials in which no behavioral response occurred, than in the 2-s pre-avoidance period on CS+ trials with responses. This "inverse' CS-related and pre-avoidance activity occurred at low incidence (< 15%) in all areas except the MD nucleus, wherein it was exhibited by 45% of the recorded units. The inverse activity may reflect the operation of local inhibitory neurons which suppress the discharges of other neurons in response to the CS-. The prevalence of inverse activity in the MD nucleus suggested an involvement of this area in behavioral inhibition.

Acoustic Stimulation↗

PubMed1996

Context-specific multi-site cingulate cortical, limbic thalamic, and hippocampal neuronal activity during concurrent discriminative approach and avoidance training in rabbits.

This study assessed the context specificity of learning-related neuronal activity: whether the same physical stimuli would elicit different neuronal responses depending on the learning situation. Neuronal activity was recorded simultaneously in six limbic areas as rabbits learned to approach a spout for water reinforcement after a tone (CS+) and to ignore the spout after a different tone (CS-). The rabbits then received avoidance training in which they learned to prevent a foot-shock by stepping in an activity wheel after one tone (CS+) and to ignore a different tone (CS-). Avoidance training sessions were alternated (1 session daily) with sessions in the well learned approach task. The tone assigned as the CS+ for approach training was the CS- for avoidance training and vice versa. The neuronal records of the anterior ventral and medial dorsal thalamic nuclei and the anterior and posterior cingulate cortices showed neuronal discrimination appropriate to the approach task during pretraining in the avoidance training apparatus with unpaired presentations of the tones and foot-shock. This finding demonstrated that the discriminative neuronal activity for approach learning was unaffected by a change in context in the pretraining session. However, context-appropriate discrimination occurred in both tasks thereafter, with the exception that medial dorsal thalamic neurons no longer showed discrimination during overtraining in the approach task. Hippocampal area CA1 neurons showed entirely context-appropriate discrimination in both tasks, with no carryover of the approach-relevant discrimination to the avoidance training apparatus. Avoidance training stage-specific peaks of training-induced excitation in different brain areas were not elicited by the same physical stimuli during concurrent approach training sessions. The results are consistent with an involvement of limbic-circuit neuronal activity in the use of context cues for mnemonic retrieval. Differential persistence of the approach-related neuronal discrimination in anterior and posterior cingulate cortex confirmed the previously hypothesized distinct mnemonic functions of these areas.

Animals↗

PubMed1996

Limbic thalamic, cingulate cortical and hippocampal neuronal correlates of discriminative approach learning in rabbits.

Previous research employing lesions and recording of neuronal activity has implicated cingulothalamic and hippocampal circuitry in the mediation of discriminative instrumental avoidance learning in rabbits. This study was directed at the question of whether the cingulothalamic circuitry is specialized for avoidance learning, or whether it is also involved in appetitively motivated learning. Multi-unit neuronal recordings in the aforementioned areas were obtained as adult New-Zealand white rabbits learned to approach and orally contact a drinking spout for water reward after a tone conditional stimulus (CS+), and to ignore the spout after a different, non-predictive tone conditional stimulus (CS-). As during avoidance learning, excitatory and discriminative training-induced neuronal activity (TIA) developed during the course of approach learning. Discriminative TIA refers to development of greater neuronal firing response to the CS+ than to the CS-. Excitatory TIA refers to increased neuronal discharge magnitude during training compared to the activity elicited before training, when CS presentations were unpaired with foot-shock presentations. As during avoidance learning, TIA in anterior cingulate cortical and interconnected mediodorsal (MD) thalamic neuronal records preceded TIA in posterior cingulate cortical and interconnected anterior ventral thalamic records. Delayed changes also occurred in area CA1 of the hippocampus in parallel with changes in the posterior cingulate cortex and the anterior thalamic nuclei. In contrast to the avoidance-related activity, the changes in the thalamic areas preceded or occurred concurrently with changes in the related cingulate cortical areas. This difference is hypothesized to be due to a reduced or absent contribution of amygdaloid efferents to the approach learning-related TIA. The overall magnitude of the elicited training-induced neuronal responses was reduced, relative to the discharges during avoidance conditioning. The discharge magnitude differences suggested a greater recruitment of limbic circuit functions during avoidance learning, possibly due to the aversiveness and high arousal associated with the avoidance task. In general, the results indicate that the circuitry formed by interconnected cingulate cortical, limbic thalamic and hippocampal neurons has fundamentally similar functions in both approach and avoidance learning.

Animals↗

PubMed1996

Neural substrates of discriminative avoidance learning and classical eyeblink conditioning in rabbits: a double dissociation.

In a previous study, lesions of the deep cerebellar nuclei blocked classical eyeblink conditioning, but did not impair discriminative avoidance learning in rabbits. Here, was also found previously, lesions of the anterior and medial dorsal thalamic nuclei severely impaired discriminative avoidance learning. However, these lesions had no impact on discriminative eyeblink conditioning or reversal learning. These results complete the demonstration of a double dissociation, indicating distinct neural substrates for the acquisition of these learned behaviors. It is proposed that the two learning circuits identified by these studies mediate, respectively, acquisition of specific adaptive reflexes and whole-body, voluntary goal-directed movements.

Animals↗

PubMed1995

Studies of the limbic comparator: limbic circuit training-induced unit activity and avoidance behavior in rabbits with anterior dorsal thalamic lesions.

Multiunit activity of cingulate cortex and the anterior ventral (AV) thalamic nucleus was recorded as rabbits learned to avoid a shock by locomoting in response to a tone (CS+) and to ignore a nonpredictive tone (CS-). Rabbits with anterior dorsal (AD) thalamic lesions avoided shock more often than controls during the first training session and the first session of extinction training given after the completion of acquisition. Training-induced neuronal changes in cingulate cortex and in components of the AV nucleus were lost in the rabbits with lesions. These effects were comparable to previously observed effects of subicular lesions. It is proposed that interactions of AD thalamic, subicular, and cingulate cortical neurons yield a stable mnemonic representation of the associative significance of the CS. The representation is used in a comparator circuit, which inhibits behavior when unexpected events occur.

Acoustic Stimulation↗

PubMed1995

Disruption of the actin cytoskeleton in budding yeast results in formation of an aberrant cell wall.

A temperature-sensitive, conditionally lethal actin mutant of Saccharomyces cerevisiae, DBY 1693, was used to study, using light and electron microscopy, dysfunction of the actin cytoskeleton in the morphogenesis of the cell wall. Cells of this mutant strain survived at least 24 h at the restrictive temperature (37 degrees C). These cells showed isodiametric growth. Mutant cells accumulated vesicles, probably as a consequence of chaotic secretory transport caused by loss of polarity. A conspicuous morphological response to the dysfunction of actin was the formation of an aberrant wall over the whole surface of the isodiametrically-growing cell. This wall was of loose texture with protruding glucan microfibrils incompletely masked with amorphous matrix. It resembled the regenerating cell wall on the surfaces of yeast protoplasts. The localization of wall synthesis over the whole surface of temperature sensitive actin mutant cells was in accordance with an even distribution of submembranous actin in the form of patches (similarly to regenerating protoplasts). Delocalization of finger-like invaginations of the plasma membrane from the bud region to the whole surface of the growing cell was also found in mutant cells.

Actins↗

PubMed1995

Mamillothalamic tract transection blocks anterior thalamic training-induced neuronal plasticity and impairs discriminative offidance behavior in rabbits.

Rabbits with bilateral transecting lesions of the mamillothalamic tract, control (tract-sparing and sham) lesions, or no lesions, and chronic, fixed-position anterior ventral (AV) and medial dorsal (MD) thalamic and posterodorsal subicular complex unit recording electrodes were trained to step in an activity wheel in response to a 0.5 sec tone (CS+) in order to avoid a brief foot shock. The rabbits also learned to ignore a different tone (CS-) not predictive of shock. Behavioral acquisition was significantly retarded in rabbits with mamillothalamic tract transection compared to controls. When trained, transected rabbits failed to avoid the shock more often than controls. Mamillothalamic tract transection abolished and control lesions attenuated AV thalamic discriminative training-induced activity (i.e., development with training of greater discharges in response to the CS+ than to the CS-). Transection and control lesions attenuated AV thalamic excitatory training-induced activity (greater elicited activity during training than during unpaired tone-shock presentations before training) as well as AV thalamic "spontaneous" baseline unit activity. CS-elicited discharge magnitude was reduced by control lesions and it was further reduced by tract transecting lesions. Significant lesion-related changes were not found in the subicular or MD thalamic neuronal receptor. Mamillothalamic tract afferent information flow is thus essential for AV thalamic discriminative training-induced activity, excitatory training-induced activity, tone-elicited discharges and maintenance of conditioned avoidance responses. The effects of the control lesions suggested that afferents which course in parallel with and near the mamillothalamic tract may contribute to AV thalamic spontaneous activity and excitatory training-induced activity.

Animals↗

PubMed1994

Afferent connections of the anterior thalamus in rabbits.

This study was designed to determine whether axons of cholinergic dorsal tegmental neurons terminate on cells in the anterior thalamus in rabbits as in other species, and to localize projecting tegmental cells for future studies of their contributions to anterior thalamic learning-relevant neuronal activity. The distribution of retrogradely labeled neurons was examined following injections of wheat germ agglutinin horseradish peroxidase (WGA-HRP) centered in the anterior ventral (AV) thalamic nucleus. The results confirm past findings in rabbits indicating projections to anterior thalamus from the mammillary nuclei, the posterior cingulate cortex, presubiculum and postsubiculum. Demonstrated for the first time in rabbits were projections from the lateral dorsal and the pedunculopontine tegmental nuclei, locus coeruleus, dorsal raphe nucleus, Gudden's dorsal tegmental nucleus, pretectum and reticular thalamic nucleus.

Afferent Pathways↗

PubMed1994

Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the inhibition of 5-alpha reductase in healthy male volunteers.

A total of 32 healthy male volunteers (age range 20-30 years) were enrolled in a 1-week open, randomized, placebo-controlled study comparing finasteride (Proscar), a 5 alpha-reductase inhibitor, with Permixon, the plant extract of Serenoa repens. The objective of the study was to evaluate the effect of single and multiple doses of the drugs on the inhibition of 5 alpha-reductase as assessed by serum dihydrotestosterone level determination. Following baseline measurements on day 1, the subjects were randomized to finasteride 5 mg once a day (n = 10), Permixon 80 mg x 2 twice a day (n = 11), or to placebo once a day (n = 11) for 7 days. Serum testosterone and dihydrotestosterone levels, were determined on day 1 (baseline and 12 h) and on days 2 (24 h), 3 (48 h), 4 (72 h), 6 (120 h), and 8 (168 h). After 12 h, a single dose of finasteride 5 mg reduced the serum dihydrotestosterone level by 65% (p < or = 0.01). The decreases ranged from -52 to -60% with multiple doses of finasteride 5 mg once a day (p < or = 0.01). As in the placebo group, there was no effect of Permixon on the serum dihydrotestosterone level. No significant difference was detected between finasteride and Permixon or between finasteride and placebo with respect to serum testosterone, except on days 3 and 6, respectively (p < or = 0.05). However, the corresponding serum testosterone levels remained within the normal ranges. These data confirm the efficacy of finasteride as inhibitor of 5 alpha-reductase.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗

PubMed1993

Comparison of finasteride (Proscar), a 5 alpha reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5 alpha reductase inhibition.

Human prostate was used as a source of 5 alpha reductase. Compounds were incubated with an enzyme preparation and [3H]testosterone. [3H]-dihydrotestosterone production was measured to calculate 5 alpha reductase activity. IC50 values (ng/ml) were finasteride = 1; Permixon = 5,600; Talso = 7,000; Strogen Forte = 31,000; Prostagutt = 40,000; and Tadenan = 63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5 alpha reductase, while Permixon and Bazoton have neither anti-androgen nor 5 alpha reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5 alpha reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 micrograms/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5 alpha reductase.

5-alpha Reductase Inhibitors↗

PubMed1993

Adherence of Serratia marcescens, Serratia liquefaciens, Pseudomonas aeruginosa and Staphylococcus epidermidis to blood transfusion bags (CPD-SAGMAN sets).

The adherence of 4 isolates of Serratia marcescens, 1 isolate of Serratia liquefaciens, 1 of Pseudomonas aeruginosa, and 2 of Staphylococcus epidermidis to blood transfusion sets (CPD-SAGMAN) consisting of bags and connecting tubing was tested. All strains adhered well to the connecting tubes (polyvinyl chloride) from the transfusion sets from 3 manufacturers. Three isolates from a Swedish outbreak of septicaemia associated with contaminated blood bags showed greater adherence than an isolate from a urinary tract infection. There was no significant adherence of S. marcescens to the blood bags. In general, there were no significant differences in the adherence of a given isolate to the plastics from different manufacturers. Appropriate hygienic procedures for the production of transfusion sets appear to be of greater importance than differences in the plastic material as regards the incidence of transfusion-related bacteremia.

Bacteremia↗

PubMed1992

Local norepinephrine depletion and learning-related neuronal activity in cingulate cortex and anterior thalamus of rabbits.

Multi-unit neuronal activity was recorded in posterior cingulate cortex (area 29) and the anterior ventral (AV) thalamic nucleus during discriminative instrumental avoidance learning wherein a response (stepping in an activity wheel) to a 0.5-s tone (CS+) prevented a foot-shock 5 s after CS+ onset. Presentations of a different tone (CS-) on 50% of the conditioning trials in an irregular sequence with the CS+ did not predict shock and thus required no response. Two groups of rabbits received intracranial micro-injections of 6-hydroxydopamine (6-OHDA) to locally deplete the NE in area 29 or the AV nucleus. Vehicle was injected in the non-depleted area in each group and a third group received vehicle injections in both areas. Dopamine neurons in subjects that received 6-OHDA were protected by pre-treatment with GBR-12909. Neuronal data were collected during two pre-training sessions in response to the tones only and when the tones and shock were presented unpaired. Thalamically depleted rabbits made more, and cortically depleted rabbits made fewer, avoidance responses than controls during the early stages of behavioral acquisition, and cortically depleted rabbits made fewer responses than controls and thalamically depleted rabbits during extinction testing administered after the completion of acquisition. One effect of NE depletion on neuronal activity was entirely local: elimination of neuronal sensitization effects (enhanced discharges elicited by tones during the unpaired tone-shock pre-training treatment relative to pre-training with tones only). Other neuronal effects of NE depletion were system-wide, i.e., they occurred whether the depletion was cortical or thalamic.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1992

The influence of congo red on the cell wall and (1----3)-beta-D-glucan microfibril biogenesis in Saccharomyces cerevisiae.

Congo red was applied to growing yeast cells and regenerating protoplasts in order to study its effects on wall biogenesis and cell morphogenesis. In the presence of the dye, the whole yeast cells grew and divided to form chains of connected cells showing aberrant wall structures on both sides of the septum. The wall-less protoplasts in solid medium with the dye exhibited an abnormal increase in volume, regeneration of aberrant cell walls and inability to carry out cytokinesis or protoplast reversion to cells. In liquid medium, the protoplasts synthesized glucan nets composed mainly of thin fibrils orientated at random, whereas normally, in the absence of dye, the nets consist of rather thick fibrils, 10 to 20 nm in width, assembled into broad ribbons. These fibrils are known to consist of triple 6/1 helical strands of (1----3)-beta-D-glucan aggregated laterally in crystalline packing. The thin fibrils (c. 4 to 8 nm wide) can contain only a few triple helical strands (c. 1.6 nm wide) and are supposed to be prevented from further aggregation and crystallization by complexing with Congo red on their surfaces. Some loose triple 6/1 helical strands (native elementary fibrils) are also discernible. They represent the first native (1----3)-beta-D-glucan elementary fibrils depicted by electron microscopy. The effects of Congo red on growth and the wall structure in normal cells and regenerating protoplasts in solid medium can be explained by the presence of a complex which the dye forms with (helical) chain parts of the glucan network and which results in a loss of rigidity by a blocked lateral interaction between the helices.

Cell Division↗

PubMed1992

DNA repair modifies the site and strand specificity of ethyl methanesulfonate mutagenesis in yeast.

The influence of DNA repair on the specificity of ethyl methanesulfonate (EMS) mutagenesis in a plasmid-borne copy of the Saccharomyces cerevisiae SUP4-o gene was investigated. Isogenic yeast strains that are repair-proficient (RAD) or defective for nucleotide excision (rad1), postreplication (rad18) or recombinational repair (rad52) were treated with EMS. Compared to the RAD wild-type, the maximum SUP4-o mutation frequency was 2-fold greater in the rad1 background whereas it was approximately 50% less in the rad18 and rad52 strains. The majority (779/788) of SUP4-o mutations characterized by DNA sequencing were single base pair changes, primarily (> 91%) G.C-->A.T transitions in the RAD, rad1 and rad18 strains. In the rad52 background, only 57% of the substitutions were G.C-->A.T transitions with transversions at G.C pairs accounting for almost all of the remaining changes. Comparisons of the distributions of single base pair substitutions in SUP4-o revealed that there was no excision repair-dependent bias for G.C-->A.T events to occur at sites flanked by a 5' or 3' A.T pair as observed previously for EMS mutagenesis of the lacIgene in Escherichia coli (Burns et al., 1986). These transitions also did not occur more often at sites where the guanine was flanked by a 5' purine than by a 5' pyrimidine. However, they exhibited a small preference for sites having the guanine on the transcribed strand in the RAD and rad52, but not rad1 or rad18, strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition↗

PubMed1992

[New aspects in the diagnosis of herpes simplex virus encephalitis--case reports and virologic findings].

Herpes simplex virus (HSV) is one of the most common causes of severe necrotizing encephalitis in men. Without adequate acyclovir treatment it has a mortality rate of 70%. An early, reliable virological diagnosis is therefore essential. In this study, two newly-introduced diagnostic methods were assessed and compared: Polymerase Chain Reaction (PCR) for detection of HSV-genome in cerebrospinal fluid and HSV-specific isoelectric focusing (IEF) for detection of intrathecal virus specific antibody synthesis in HSV encephalitis (HSVE). PCR proved more effective for the early diagnosis of HSVE and HSVE relapses, whereas HSV-specific IEF was superior for the diagnosis of HSVE in post-acute stages of the disease.

Adolescent↗

PubMed1991

Training-stage related neuronal plasticity in limbic thalamus and cingulate cortex during learning: a possible key to mnemonic retrieval.

This study is part of an ongoing project concerned with the analysis of the neural substrates of discriminative avoidance learning in rabbits. Multi-unit activity was recorded in 5 anterior and lateral thalamic nuclei and in 4 layers of 2 posterior cingulate cortical areas (29c/d and 29b) during learning. The rabbits learned to step in response to a warning tone to avoid a foot-shock, and to ignore a different tone not followed by shock. Excitatory training-induced unit activity (TIA, increased tone-elicited activity during training relative to a pretraining session with unpaired tone-shock presentations) and/or discriminative TIA (greater discharges to the warning than to the safe tone) developed during training in 11 of the 13 areas. Discriminative TIA in the thalamic nuclei increased monotonically as learning occurred. Anterodorsal (AD) thalamic excitatory TIA peaked in an early stage (the first session of training), laterodorsal thalamic and parvocellular anteroventral (AVp) excitatory TIA peaked in an intermediate stage (the session of the first behavioral discrimination), and magnocellular anteroventral (AVm) and anteromedial (AM) thalamic excitatory TIA peaked in a late stage (the session in which asymptotic behavioral discrimination first occurred). The excitatory TIA in these nuclei declined as training continued beyond the stage in which the peak occurred. Peaks of excitatory TIA developed in area 29c/d of posterior cingulate cortex in the early (layer IV), intermediate (layers I-III and V) and late (layer IV) training stages, as just defined. Only layer IV in area 29b of posterior cingulate cortex exhibited a peak of excitatory TIA, which occurred in the early and intermediate training stages. As in limbic thalamus, discriminative TIA increased monotonically over training stages in layers V and VI of areas 29c/d and in layer VI of area 29b. However, layers I-III and IV in area 29c exhibited peak discriminative TIA in the intermediate and late training stages, respectively. Lesion studies indicate that limbic thalamus and cingulate cortex are essential for learning. The peaks represent a unique topographic pattern of thalamic and cortical excitation elicited by the CS+. It is proposed that the peaks constitute a retrieval pattern, i.e. a unique topographic array of excitation. This pattern encodes the spatio-temporal context which defines the learning situation and is necessary for recall and output of the learned response.

Animals↗

PubMed1991

Cerebellar interpositus nucleus lesions disrupt classical nictitating membrane conditioning but not discriminative avoidance learning in rabbits.

Cerebellar interpositus nucleus lesions were given to 14 rabbits trained in two behavioral paradigms; discriminative avoidance conditioning of locomotor behavior and classical nictitating membrane conditioning. Bilateral lesions that prevented acquisition of the classically conditioned response on both the left and right side failed to affect the acquisition or performance of the conditioned discriminative avoidance response. The results are discussed in terms of differences in neural substrates that apparently subserve the two forms of learning.

Animals↗