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Biomedical subjects

M Gabriel

Publications and source records attributed to M Gabriel.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

[Surgical therapy of primary hyperparathyroidism in newborn infants].

This is a report on a neonatal primary hyperparathyroidism (NPHPT) treated by total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm musculature. Histologically, the glands were composed of a "chief cell hyperplasia" of the parathyroid tissue. Clinical manifestation in neonates and differential diagnosis of HPT are discussed. Indication for operation and surgical procedure are described.

Humans↗

Class-specific antibody response to pneumococcal capsular polysaccharides in men infected with human immunodeficiency virus type 1.

We characterized the effect of infection with human immunodeficiency virus type 1 (HIV) on levels of total immunoglobulins and pneumococcal vaccine-specific immunoglobulins in 28 heterosexual and 25 homosexual men seronegative for HIV; 27 asymptomatic, seropositive homosexual men; and 21 patients with AIDS. Total serum IgG levels were increased in both HIV-seropositive groups compared with the HIV-seronegative men (P less than .001). Total IgM levels, however, were elevated only in the asymptomatic, HIV-seropositive men (P less than .08); total IgA levels were elevated only in the patients with AIDS (P less than .05). Vaccine-specific serum IgG, IgM, and IgA significantly increased over baseline three and six weeks after immunization in all groups (P less than .05). Responses to vaccine among the HIV-seronegative groups were similar but were greater for all antibody classes than were responses among the HIV-seropositive groups (P less than .05).

Acquired Immunodeficiency Syndrome↗

Long-term follow-up of patients treated with VVI pacing and sequential pacing with special reference to VA retrograde conduction.

The aim of this prospective study is comparing long-term prognosis in patients implanted with a VVI pacemaker (group A) with those implanted with a sequential pacing device, AAI or DDD, (group B). Both groups of 45 patients each, were comparable as regards to age, sex, pacing indications, underlying heart disease, and technical conditions of implantation and were followed-up over 55 months. Atrial arrhythmias (A.A.) incidence was higher in group A: 24.4% than group B: 8.8% (P less than 0.05). Arterial embolisms (A.E.) occurred in group A patients only. Worsening or occurrence of exercise limitation was more frequent in group A: 35.6% as compared to group B: 13.3% (P less than 0.05) and deaths related to these complications, occurred in seven cases in group A versus four cases in group B. In group A, all patients who experienced a worsening or occurrence of an A.A. or an A.E., had a ventriculoatrial conduction (VAC). No statistical difference was observed in worsening or occurrence of exercise limitation between patients with VAC and those without VAC: nine (42.8%) and seven (29.2%) but they respectively experienced at least one complication in 16 cases (76.2%) and seven cases (29.2%) (P less than 0.01). In conclusion, long-term prognosis in patients implanted with VVI pacing as compared to patients implanted with sequential pacing is poorer. The presence of VAC in patients treated with permanent VVI pacing is a major factor for complications and deaths related to A.E. and cardiac failure. Thus VVI pacing should be avoided in patients with VAC.

Arrhythmias, Cardiac↗

[Van der Woude syndrome in combination with ring chromosome 18].

7-month-old girl with a combination of van der Woude syndrome and ring chromosome 18 showed the following malformations: medial palate cleft, fistulas of the lower lips, hypertelorism, epicanthus, antimongoloid position of the eyelids, a small hymenal appendix, plantar placing of the third toe, atrial septum defect, stenosis of the auditory canal. The combination of fistulas of the lower lip and cleft lip or palate already established the diagnosis of Van der Woude Syndrome. Because of the additional malformations observed a chromosome analysis was performed which demonstrated a ring chromosome 18. The phenotypic features of ring-chromosome 18, a 18p-/18q- syndrome, vary according to the extend of deletion of the short or long arm. However, all patients show craniofacial dysmorphism, intellectual and developmental retardation, defective hearing, speech disorder, and more than 50% have stenosis or atresia of the auditory canal.

Abnormalities, Multiple↗

Posterior cingulate cortical lesions eliminate learning-related unit activity in the anterior cingulate cortex.

The frequency of multi-unit neuronal firing in response to tonal conditional stimuli increases, and the neuronal responses become discriminative in character, in the anterior and posterior subfields of the cingulate cortex (Brodmann's Area 24 and 29, respectively) during the course of discriminative avoidance conditioning in rabbits. Bilateral electrolytic lesions of the dorsal subicular complex eliminated the training-induced excitatory response in both cortical subfields, suggesting that subiculocortical projection fibers are essential for this effect. Yet, available data indicate that the subicular projection reaches only Area 29, not Area 24. Here we test the hypothesis that the subicular influence attains Area 24 via a synaptic relay in Area 29. The results showed in keeping with the hypothesis, that bilateral aspirative or electrolytic lesions in Area 29 eliminated the training-induced neuronal responses in Area 24. As in the case of subicular lesions, the Area 29 lesions increased the amplitude of the macropotentials in Area 24. These results are discussed in relation to a model of the interactions of the cingulate cortex, hippocampus and the limbic thalamic nuclei during learning.

Animals↗

Hippocampal control of cingulate cortical and anterior thalamic information processing during learning in rabbits.

Past studies of the neural determinants of discriminative avoidance conditioning in rabbits have fostered a theoretical model that describes the interactive functioning of the cingulate cortex (Brodmann's Areas 24 and 29), the anterior ventral and medial dorsal thalamic nuclei (AVN and MDN) and the hippocampus. Here we test hypotheses of the model concerning the influence of the hippocampus on cortical and thalamic information processing. The rabbits learned to perform locomotory conditioned responses (CRs) in an activity wheel in response to an acoustic (pure tone) positive conditional stimulus (CS+). A shock unconditional stimulus (US) was given 5 s after CS+ onset, but locomotion during the CS+ - US interval prevented the US. The rabbits also learned to ignore a second tone (a negative conditional stimulus, CS-) of different auditory frequency than the CS+, that did not predict the US. Multi-unit activity and intracranial macropotentials were recorded in the cingulate cortex and the AVN during acquisition, overtraining, extinction, reacquisition and reversal training. Data were obtained in intact rabbits and in rabbits with bilateral lesions of the subicular complex, the origin of projections of the hippocampal formation to the cingulate cortex and AVN. In addition, the activity in the AVN was recorded in a separate group of rabbits with posterior cingulate cortical (Area 29) lesions. Subicular and Area 29 lesions were associated with an enhancement of the training-induced CS+ elicited neuronal response in the AVN. The frequency of CRs was enhanced in animals with subicular lesions. CS elicited unit responses in the cingulate cortices were attenuated in rabbits with subicular lesions. Both of the lesions were associated with significantly increased amplitudes of the CS elicited average cortical and thalamic macropotentials. These results suggested the following conclusions: subiculocortical afferents provide an enabling influence that is essential for CS elicited excitation in the cingulate cortex; the cingulate cortical excitatory response in intact animals exerts a limiting influence on the activity in the AVN; the enhanced AVN neuronal response in rabbits with lesions is due to the absence of the limiting influence and it contributes to the increased CR frequency in those animals. It is hypothesized that the hippocampus via subiculocortical projections, governs the flow of CR-inducing thalamocortical excitatory volleys. This governance determines the timing of CR output. The results of hippocampal processing of contextual information acting through the subiculocortical projection determines the moment most appropriate for the CR.

Acoustic Stimulation↗

Melioidosis: a serological survey in a tuberculosis sanatorium in Hong Kong.

A serological survey of 275 Chinese patients with underlying pulmonary diseases in a tuberculosis sanatorium in Hong Kong showed that 39 (14%) had haemagglutinating antibody (HA) against Pseudomonas pseudomallei in a titre of 1: 80 or above. Only 9 of these 39 patients had travelled to endemic areas, suggesting that at least 30 patients (11%) had been exposed to Ps. pseudomallei locally. Females are affected as often as males, and the seropositive rate is the same whether patients are immunosuppressed or not. Because subclinical melioidosis is prevalent and HA may persist for a long time, even at a high titre, after infection, determination of HA alone cannot differentiate between active melioidosis and its masquerade--active tuberculosis.

Adolescent↗

Unexpected findings amongst the skin test responses to mycobacteria of BCG vaccinated Kuwaiti school children.

A multiple skin test survey was carried out in Kuwait on 1200 school children aged 8-11 years, and on 1228 children aged 12-16 years. With only 15 exceptions, all these children had received vaccination with Japanese BCG just before they started school, 5 years and 9 years earlier respectively. Tuberculin positivity was almost 90% in both groups, with a mean response size of 8.7 mm. This was associated with remarkably high responsiveness to many of the other mycobacterial species investigated. Since this high reactivity was also to Mycobacterium ulcerans, a species most unlikely to be present in Kuwait, it is proposed that this might be due to responsiveness to group ii antigen which is present in all slow growing species. Only M. flavescens and M. rhodesiae amongst the fast growing species, were absent as sensitising organisms. After correction for the supposed reactivity to group ii antigen, M. avium B, M. gordonae, M. ulcerans and M. xenopi amongst the slow growing species, also appeared to be absent from the Kuwait environment. The species most commonly encountered were M. leprae, M. chitae, M. neoaurum, M. diernhoferi, and M. vaccae in this order. This was a remarkable finding for a country assumed to be poor in contact with environmental species, and known to have a very low prevalence of leprosy. As previously reported from Iran, but not confirmed in other places, there was a 95% correlation between responsiveness to Leprosin A and Vaccin. Amongst the slow growing species M. avium A, M. intracellulare, and M. kansasii appear to be frequent sensitising agents, in common with many other places.

Adolescent↗