Biomedical subjects

M Gabriel

Publications and source records attributed to M Gabriel.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1991

Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits.

Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS-) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS- (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and declined during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning.

Amygdala↗

PubMed1991

Effects of cingulate cortical lesions on avoidance learning and training-induced unit activity in rabbits.

This study extends an ongoing analysis of the neural mediation of discriminative avoidance learning in rabbits. Electrolytic lesions encompassing anterior and posterior cingulate cortex (area 24 and 29) or ibotenic acid lesions in area 24 only were made prior to avoidance conditioning wherein rabbits learned to step in response to a tone conditional stimulus (CS+) in order to avoid a brief, response-terminated 1.5 mA. foot-shock unconditional stimulus (US). The US was presented 5 s after CS+ onset, in the absence of a prior stepping response. The rabbits also learned to ignore a different tone (CS-) not followed by the US. Multi-unit activity of the caudate and medial dorsal (MD) thalamic nuclei, projection targets of the cingulate cortex, was recorded during learning in all rabbits. Activity was also recorded in area 29 in the rabbits with area 24 lesions. Learning in rabbits with combined lesions was severely impaired and it was moderately retarded after lesions in area 24. MD thalamic and caudate training-induced neuronal discharge increments elicited by the CS+ were enhanced in rabbits with lesions, suggesting a suppressive influence of cingulate cortical projections on this activity. Early-, but not late-developing training-induced unit activity in area 29c/d was absent in rabbits with area 24 lesions, indicating that area 24 is a source of early-developing area 29 plasticity. These results are consistent with hypotheses of a theoretical working model, stating that: a) learning depends on the integrity of two functional systems, a mnemonic recency system comprised by circuitry involving area 24 and the MD nucleus and a mnemonic primacy system comprised by circuitry involving area 29 and the anterior thalamic nuclei; b) corticothalamic information flow in these systems suppresses thalamic CS elicited activity in trained rabbits; c) corticostriatal information flow is involved in avoidance response initiation. An absence of rhythmic theta-like neuronal bursts in area 29b in rabbits with area 24 lesions is attributable to passing fiber damage.

Animals↗

PubMed1991

Cell surface structures in osmotically fragile mutants of Saccharomyces cerevisiae.

Mutants of Saccharomyces cerevisiae characterized by osmotic fragility showed a marked fibrillar structure on the inner wall surface when studied by two electron microscopic techniques, i.e. freeze-etching of whole native cells and metal shadowing of isolated cell walls. The walls of the mutant cells were more permeable to macromolecules than were those of the wild-type parental strain. The synthesis and assembly of (1----3)-beta-D-glucan wall microfibrils studied in protoplasts of mutant cells were not impaired. It is suggested that the osmotic fragility of the mutant cells is related to the deficiency of the wall structure as a consequence of the srb1 mutation affecting biogenesis of the amorphous (glucan) component.

Cell Membrane↗

PubMed1991

Muscarinic receptor binding increases in anterior thalamus and cingulate cortex during discriminative avoidance learning.

Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OXO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OXO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OXO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OXO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OXO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OXO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OXO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Scopolamine but not haloperidol disrupts training-induced neuronal activity in cingulate cortex and limbic thalamus during learning in rabbits.

Rabbits previously trained to asymptotic performance of discriminative active avoidance behavior (n = 8) received systemic injections of scopolamine hydrobromide (SH: 1.0, 2.0, or 4.0 mg/kg) and scopolamine methylbromide (SM: 4.0 mg/kg). Each rabbit received all of the doses in a counterbalanced order. Single injections were administered 30 min before daily training sessions in which the multi-unit activity in the cingulate cortex and anterior thalamus was recorded. A single session in which saline was administered prior to testing preceded each of the drug sessions, and two days without training followed each drug session to allow dissipation of the drug effects. Additional groups received injections of haloperidol (HA: 0.025, 0.10, or 0.40 mg/kg; n = 7), or both SH/SM and HA (n = 5). The rabbits had been trained to step in an activity wheel in response to a tone CS + to avoid a footshock unconditional stimulus (US), and to ignore a different tone not followed by the US. SH and HA, but not SM, reduced significantly the frequency of conditioned avoidance responses (CRs). All doses of SH significantly attenuated cingulate cortical and AV thalamic training-induced neuronal discharges. HA injections also impaired CR performance but had no effect on the neuronal activity. These results suggest that the loss of the neuronal responses is contributory to the SH-induced CR loss. Absence of an effect of HA on neuronal activity indicates that the HA-induced CR impairment is due to disruption of other neural systems.

Animals↗

PubMed1990

An investigation of patients with pulmonary tuberculosis in Kuwait in preparation for studies of immunotherapy with Mycobacterium vaccae.

Sixty-five patients, many of them immigrant to Kuwait, with bacteriologically proven, adult type, pulmonary tuberculosis were studied by many parameters over the 4 months following diagnosis. Twelve were infected with tubercle bacilli resistant to at least one anti-tuberculosis drug. Preliminary evidence suggested that this was frequently primary resistance in patients infected in their countries of origin. The Kuwaiti environment results in very high skin test and lymphocyte proliferative responses (LTT) to shared and species specific antigens of mycobacteria in healthy persons. In comparison, patients with tuberculosis lacked cellular responses to group i and group ii antigens, but had increased IgG and IgA binding to mycobacterial antigens in general. LTT responses to added interleukin 2, and production of alpha interferon, were normal in our patients, but induction of gamma interferon in response to phytohaemagglutinin was reduced initially, rising towards normal during treatment. Biochemical and haematological abnormalities present at the time of diagnosis rapidly corrected. The disease differed from that reported in most previous studies in that fever was uncommon, the disease was never fatal, and most tuberculin tests were not necrotising. This implied that a detrimental immunopathological component is less pronounced in those exposed to the Kuwaiti environment, and a hypothesis is put forward to explain this.

Adolescent↗

PubMed1990

Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis.

47 patients with adult-type pulmonary tuberculosis attending the Chest Diseases Hospital in Kuwait were given a single injection of 10(9) irradiation-killed M. vaccae after 1 month of a 9-month course of chemotherapy. The patients were followed-up for 3 more months in double blind comparison with 65 patients given an injection of saline (placebo). The immunotherapeutic injection produced a small local lesion in 44/47 patients, 18 of which ulcerated and produced small scars. Immunotherapy made no measurable difference to the bacteriological, biochemical, haematological, or radiological parameters measured. However it was associated with significantly improved weight gain, reduced size of skin test response to Tuberculin, increased lymphocyte proliferation to common mycobacterial antigens, and increased antibody levels to mycobacterial antigens. The changes in skin test and LTT responses were related and occurred in 29% of patients whose recognition of common mycobacterial antigens returned to normal. The remaining patients did not differ in these respects from those receiving placebo. The proportion of patients whose responses were improved was very similar to that achieved using the same immunotherapeutic agent in a group of treated multibacillary leprosy patients.

Adolescent↗

PubMed1990

Improved immunotherapy for pulmonary tuberculosis with Mycobacterium vaccae.

We previously demonstrated that a single intradermal injection of 10(9) irradiation-killed M. vaccae, given 1 month after starting chemotherapy, caused significant changes in responses to mycobacterial antigens. Amongst 38 patients with pulmonary tuberculosis, 29% had lymphocytes responding to common myocobacterial antigens after the injection, compared with only 11% of 49 similar patients after an injection of saline (p less than 0.03). To increase the proportion of responders to these antigens, six modifications of the potentially immunotherapeutic injection, randomized with injections of saline, have been assessed by biochemical, clinical, haematological, immunological and radiological criteria. Subsequent lymphocyte proliferation to mycobacterial antigens enabled the modifications to be ranked in order of efficacy. Tuberculin plus murabutide plus 10(9) irradiated M. vaccae (36% of 25), an autoclaved preparation of 10(9) M. vaccae (45% of 22), and 2 x 10(9) irradiated M. vaccae (75% of 12) were the most effective. Antibody responses in several IgG subclasses to mycobacteria, but not streptococci, were also significantly increased by the most effective modifications over the 8 weeks following injection. Detailed radiological study showed that use of the autoclaved bacilli was followed by a delay in clearing of consolidation, but by better closing of cavities than was found in the control group, suggesting enhanced, or altered, immunological activity around the lesions.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1990

Factors of prognostic significance in Chinese children with tuberculous meningitis.

A study was undertaken to identify factors of prognostic importance for 199 Chinese children with tuberculous meningitis treated in Hong Kong between 1961 and 1984 inclusive. During the period under study rifampicin and then pyrazinamide were introduced into treatment regimens and intrathecal therapy was abandoned. An analysis of pretreatment characteristics and details of chemotherapy by multivariate logistic regression identified two independent variables that predicted prognosis, namely clinical stage at the time of diagnosis, and age. Changes in treatment policies and the introduction of new anti-tuberculosis drugs did not appear to influence prognosis.

Adolescent↗

PubMed1990

Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits.

Neuronal activity in cingulate cortex was recorded during discriminative active avoidance conditioning of rabbits. In one subpopulation of neurons, brief (200 and 500 ms) conditional stimuli (CSs) elicited greater average cingulate cortical training-induced neuronal discharges during conditioned response acquisition than did a long (5,000 ms) CS, and the amount of neuronal discrimination between CS+ and CS- was greater in response to the brief CSs than to the long CS. Neurons in a different subpopulation did not encode CS duration per se but were sensitive to the novelty of the CS duration. Medial dorsal and anteroventral thalamic neurons were suppressed by novel CS durations that activated novelty-sensitive neurons in related cingulate cortical areas. These results are discussed in relation to a theoretical model of the neural mediation of avoidance conditioning.

Animals↗

PubMed1990

Functions of anterior and posterior cingulate cortex during avoidance learning in rabbits.

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Acoustic Stimulation↗

PubMed1990

[Subclinical course of Epstein-Barr virus infection in infants with transient hepatitis].

Epstein-Barr-Virus-(EBV)-infections are well known to cause acute infectious mononucleosis in adolescents and young adults. However in early infancy and childhood these infections are usually mild and clinically inapparent. In the following we describe a case of a primary EBV-infection in infancy, which led to a transient hepatitis, identified by pathologically elevated liver enzymes.

Antibodies, Viral↗

PubMed1990

Model of redox regulation of hyper- or hypothyreoidism.

Since the triiodothyronine (T3) shifts the tissue metabolism to oxidative direction, one should await that in hyperthyreoidism caused by T3 an oxidosis will be formed, whilst in hypothyreoidism called forth by subtotal thyreoidectomy, redosis will be emerged. However, according to our experiments these interrelationships proved to be inverse. These "paradoxal" changes of redox-state are the consequences of the flowing redox compensations elicited by the tissue redox-buffer capacity (RBC). The pathomechanism can be modelled with differential equation (computer analysis). The redox-state changes are characteristics in each tissues. Between the RBC of the tissue and the shift of redox-state potential (E'0) there is a negative correlation. As an autoregulatory mechanims, the redosis formed in hyperthyreoidism will increase the hormone synthesis in the thyroid gland, while the oxidosis after hypothyreoidism will decrease the synthesis. In other words, these processes strengthen each other. Changes of the heart frequency show correlation with the E'0, and can be described by differential equation. Our theoretical model for the redox regulation might answer also the question of the reversibility-irreversibility range of the autoregulation in the pathomechanism.

Animals↗

PubMed1989

Anterior and medial thalamic lesions, discriminative avoidance learning, and cingulate cortical neuronal activity in rabbits.

Four groups of male albino rabbits were trained to perform a conditioned response (CR, stepping in an activity wheel) to an acoustic (pure tone) conditional stimulus (CS+). A 1.5-2.0 mA shock unconditional stimulus (US) delivered through the grid floor of the wheel was administered 5 s after CS+ onset, but stepping during the CS-US interval prevented the US. The rabbits were also trained to ignore a second tone (a negative conditional stimulus or CS-) of different auditory frequency than the CS+, that was presented in an irregular order on half of the conditioning trials but never followed by the US. One group had bilateral electrolytic lesions in the medial dorsal (MD) thalamic nucleus, a second group had combined bilateral lesions in the MD and the anterior thalamic nuclei, and a third group had no lesions. The fourth group was composed of rabbits with combined lesions that resulted in only partial damage in the anterior and MD nuclei. In all rabbits, multi-unit activity and field potentials were recorded from the cingulate cortical projection targets of the MD and anterior nuclei. The average rate of acquisition in rabbits with MD and partial lesions was not significantly different from that in controls, but the asymptotic performance in rabbits with lesions was significantly impaired, relative to that in controls. None of the rabbits that had the combined MD and anterior thalamic lesions reached the acquisition criterion. The average proportion of trials in which these rabbits performed avoidance responses during their final training sessions was 0.3, compared to 0.8 in controls. The unconditioned response was not significantly affected by the lesions, nor was there any indication that the lesions impaired the sensory processing of the CSs. These results and the massive training-induced neuronal discharges shown in past studies to occur in the limbic thalamic neurons indicate that these neurons are importantly involved in the circuitry that mediates discriminative avoidance conditioning in rabbits. The training-induced neuronal activity in cingulate cortex was dramatically attenuated in rabbits with lesions. Differences in the degree of this attenuation between lesion conditions and with respect to training stages were discussed in relation to a theoretical working model of limbic thalamic and cingulate cortical associative functions.

Acoustic Stimulation↗

PubMed1989

Conditional stimulus probability and activity of hippocampal, cingulate cortical, and limbic thalamic neurons during avoidance conditioning in rabbits.

Past studies of the neuronal correlates of avoidance conditioning in rabbits have led to a model of information flow among structures of the limbic system. A hypothesis of the model is that unexpected stimuli activate certain hippocampal and cingulate cortical neurons. This activity in turn suppresses or "limits" the firing of limbic thalamic neurons. This hypothesis is tested in relation to stimuli classified as unexpected or expected on the basis of their incidence or "probability." Multi-unit and field potential responses in the anterior and posterior cingulate cortices (AC and PC), the dentate gyrus (DG), and the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei were recorded during the acquisition and performance of a locomotor conditioned response (CR). The CR, stepping in an activity wheel in response to a 0.5-s tone (CS+), prevented the occurrence of a shock US scheduled 5 s after CS+ onset. The rabbits also learned to ignore a different tone (CS-), not predictive of the US. Training was given daily (120 trials, 60 with each CS in an irregular sequence) until behavioral discrimination reached criterion. After criterion, asymmetric probability (AP) sessions were given, in which the CS+/CS- proportions were .2/.8 or .8/.2. The AP sessions were the same as conditioning sessions except for the probability manipulation. A significant discriminative response, i.e., a greater neuronal discharge to the CS+ than to the CS-, developed in all regions during behavioral acquisition. The unit response in the AP sessions was enhanced in all areas by rare presentation of the CS-, compared with the equal and frequent CS- conditions. Rare presentation of the CS+ enhanced the unit response in the cortical areas (AC, PC, and DG), but it suppressed the firing of limbic thalamic (AV and MD) neurons. These results were supportive of the model. Rare CS+ presentations did not alter AV and PC neuronal activity in rabbits with subicular lesions, a result suggesting that an intact hippocampus is essential for normal neuronal responses to stimulus probability in the cingulate cortex and limbic thalamus.

Animals↗

PubMed1989

HLA-DR and tuberculin tests in rheumatoid arthritis and tuberculosis.

Responses to four new tuberculins were found to be significantly reduced in 46 patients with rheumatoid arthritis in comparison with a control group of 79. Except for tuberculin itself, the same was found in 111 patients with tuberculosis. In common with patients with tuberculosis and leprosy, those with rheumatoid arthritis did not respond to common mycobacterial (group i) antigen. Three DR haplotypes were found to have significant effects on skin test responsiveness of the rheumatoid patients but had little or no effect on that of the patients with tuberculosis and none on that of the healthy control group. Rheumatoid patients with the HLA-DR4 haplotype had significantly greater responses to all four reagents than did non-DR4 patients, but their responses to leprosin A and scrofulin remained significantly lower than those of the control group. Possession of HLA-DR3 haplotype was associated with skin test positivity approaching normal, but the sizes of responses were reduced. Possession of DR7 was associated with an unexpected reduction in skin test positivity, especially in the case of tuberculin. These results support the hypothesis that mycobacteria, or autoantigens cross reactive with mycobacteria, may be involved in the aetiology of rheumatoid arthritis. The results also show that the regulation and specificity of responsiveness to mycobacterial antigens are different in patients with rheumatoid arthritis with different HLA-DR haplotypes.

Adolescent↗