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Biomedical subjects

B Polla

Publications and source records attributed to B Polla.

At least 19 recordsLinked to original sources

Respiratory muscle fibres: specialisation and plasticity.

Skeletal muscles are composed of fibres of different types, each type being identified by the isoform of myosin heavy chain which is expressed as slow 1, fast 2A, fast 2X, and fast 2B. Slow fibres are resistant to fatigue due to their highly oxidative metabolism whereas 2X and 2B fibres are easily fatiguable and fast 2A fibres exhibit intermediate fatigue resistance. Slow fibres and fast fibres are present in equal proportions in the adult human diaphragm while intercostal muscles contain a higher proportion of fast fibres. A small fibre size, abundance of capillaries, and a high aerobic oxidative enzyme activity are typical features of diaphragm fibres and give them the resistance to fatigue required by their continuous activity. Because of their fibre composition, intercostal muscles are less resistant to fatigue. The structural and functional characteristics of respiratory muscle fibres are not fixed, however, and can be modified in response to several physiological and pathological conditions such as training (adaptation to changes in respiratory load), adaptation to hypoxia, age related changes, and changes associated with respiratory diseases. The properties of respiratory muscle fibres can also be modified by pharmacological agents such as beta2 agonists and corticosteroids used for the treatment of respiratory diseases.

Adrenergic beta-Agonists↗

Effects of the beta(2)-agonist clenbuterol on respiratory and limb muscles of weaning rats.

The aim of this study was to analyze the effects of chronic administration of the beta(2)-agonist clenbuterol (1.5 mg x kg(-1) x day(-1) for 4 wk in the drinking water) on respiratory (diaphragm and parasternal intercostal) and hindlimb (tibialis and soleus) muscles in young rats during postnatal development (21 to 49 postnatal days). The treatment resulted in very little stimulation of muscle growth. Significant slow-to-fast transitions in the expression of myosin heavy chain isoforms and significant increases in the myofibrillar ATPase activity were found in the diaphragm and soleus, whereas tibialis anterior and intercostal muscles did not show any significant fiber-type alteration. Decrease of oxidative enzyme activities and increase of glycolytic enzyme activities were also observed. It is concluded that whereas the growth stimulation is age dependent and only detectable in adult rats, the fiber-type transformation is also present in weaning rats and particularly evident in the soleus and diaphragm. The fiber-type transformation caused by clenbuterol might lead to an enhancement of contractile performance and also to a reduced resistance to fatigue.

Adenosine Triphosphatases↗

Induction of ferritin and heat shock proteins by prostaglandin A1 in human monocytes. Evidence for transcriptional and post-transcriptional regulation.

Prostaglandins of the A type (PGA) exert a cytoprotective activity during hyperthermia and virus infection. This effect is associated with induction of heat shock proteins (HSP) in mammalian cells. We now report that, in human monocytes, PGA1 is able to induce the synthesis of the iron-binding, redox-regulated protein ferritin. L-chain ferritin induction is consequent to a substantial increase in the accumulation of L-chain ferritin transcripts in PGA1-treated cells, whereas H-chain ferritin is regulated post-transcriptionally, consequently to reduction of iron-regulatory protein binding to iron-responsive elements in ferritin mRNA. Ferritin induction is specific for cyclopentenone prostaglandins (PGA1, PGA2, PGJ2, Delta12-PGJ2), whereas other arachidonic acid (AA) metabolites have no effect. In human monocytes, PGA1 also induces heat shock gene transcription via heat shock factor activation, as well as the synthesis of the oxidative-stress protein heme oxygenase (HOS). Differently from HSP, the induction of ferritin by PGA1 is specific for monocytes. Monocytes/macrophages play a pivotal role in inflammation, controlling iron metabolism and releasing a variety of mediators, including proinflammatory reactive oxygen species (ROS), cytokines and AA metabolites. As ferritin, together with hsp70 and HO, plays a key role in protection from oxidant damage, these results suggest that PGA1 may have cytoprotective activity also during oxidative injury.

Arachidonic Acid↗

[Occupational activities and allergic respiratory manifestations].

The authors review aspects of occupational asthma that are important for the practitioner. Insurance problems are dealt with in the light of local regulations. Detailed chapters are devoted to baker's asthma (various aeroallergens), to plastic workers and painters (isocyanates) and to respiratory diseases among farmers. Finally, a list of other occupations in which asthma typically occurs is given. The responsibility of practitioners in charge of young patients about to choose their future profession is underlined.

Agricultural Workers' Diseases↗

Direct depressant effect of phosphodiesterase inhibitors on ATPase activity of rat cardiac myofibrils.

The aim of this study was to determine (i) whether phosphodiesterase inhibitors influenced ATPase activity of maximally calcium activated cardiac myofibrils and (ii) whether this effect varied in relation to isomyosin composition. Myofibrils were prepared from ventricular myocardium of 2- to 3-month-old rats. ATPase activity was determined at low ionic strength at high (> 7.5) and low (4.4) pCa. Five compounds (amrinone, milrinone, enoximone, piroximone, and rolipram) were examined at concentrations between 10 microM and 1 mM. The results obtained showed that only milrinone and amrinone inhibited ATPase activity; inhibition was dose dependent, and milrinone was more potent than amrinone. To assess whether isomyosin composition might influence the responsiveness of myofibrils to phosphodiesterase inhibitors, the effect of 1 mM milrinone was also determined in myofibrils from hypothyroid rats. According to previous observations hypothyroidism caused an isomyosin shift from V1 to V3 in rat ventricular myocardium. The inhibitory effect of milrinone was lower in myofibrils prepared from hypothyroid rats than in myofibrils from euthyroid rats.

Adenosine Triphosphatases↗

Early hydrogen peroxide-induced pulmonary endothelial cell dysfunction: detection and prevention.

OBJECTIVES: To determine a) whether hydrogen peroxide-induced, early lung endothelial cell dysfunction can be detected in an isolated, perfused, rat lung model; and b) whether the organic phosphothioate N-(2-mercaptoethyl)-1,3-propanediamine, which protects cells in culture against hydrogen peroxide-mediated damage, can exert the same protection in this model. DESIGN: Intervention study; before-after trial. SETTING: Research laboratory. MODEL: Isolated, perfused, rat lung model. INTERVENTION: Continuous hydrogen peroxide infusion at increasing concentrations and infusion times, preceded or not by a N-(2-mercaptoethyl)-1,3-propanediamine infusion. MEASUREMENTS AND MAIN RESULTS: Early pulmonary endothelial cell alterations, assessed by the lung extraction (% extraction) of 123I-metaiodobenzylguanidine. Permeability edema by % extraction of 125I-human serum albumin and the lung dry-to-wet weight ratio. Control experiments: % extraction-123I-metaiodobenzylguanidine: 21.7 +/- 3.8% (n = 7). With increasing concentrations of hydrogen peroxide (0.025, 0.125, 0.5, and 2 mmol), % extraction-123I-metaiodobenzylguanidine was progressively depressed (n = 28, ANOVA, p < .05), significantly decreased from controls at 2 mmol (10.2 +/- 5.0%, n = 7, p < .05). When the 2-mmol hydrogen peroxide infusion was preceded by the N-(2-mercaptoethyl)-1,3-propanediamine (2 mmol) infusion, % extraction-123I-metaiodobenzylguanidine (19.9 +/- 2.9%, n = 5) was not significantly different from controls (n = 7) and was significantly greater than after the 2-mmol hydrogen peroxide infusion alone (8.7 +/- 7.4%, p < .05, n = 8). In all experiments, % extraction of human serum albumin ratio and dry-to-wet weight ratio were not significantly different from that of controls. CONCLUSIONS: a) Hydrogen peroxide-induced lung endothelial cell dysfunction was detected at an early stage, before any permeability defect appeared; b) N-(2-mercaptoethyl)-1,3-propanediamine protected against such damage.

Amifostine↗

Cortisone-induced changes in myosin heavy chain distribution in respiratory and hindlimb muscles.

In this study the effects of administration of cortisone acetate (100 mg kg-1 body weight subcutaneously for 11 days) on distribution and cross-sectional area of different fibre types of rat skeletal muscles were investigated. Diaphragm, parasternal intercostal (PI), extensor digitorum longus (EDL) and soleus muscles were examined in cortisone treated animals (CA) in comparison with ad libitum controls (CTRL) and pair-fed (PF) controls. Four fibre types (I or slow and IIA, IIX, IIB or fast) were identified on the basis of their myosin heavy chain composition using a set of monoclonal antibodies. In CA rats the reduction of cross-sectional area was above 30% in IIX fibres of diaphragm, IIB fibres of PI and in all fast fibres of EDL. In all muscles slow fibres were spared from atrophy. Significant variations in fibre type distribution were found in the muscles of CA rats when compared to CTRL. The percentage of IIB fibres decreased in EDL, PI and diaphragm. This decrease was accompanied by an increase in the percentage of IIA fibres in the same muscles. No changes in the percentage of slow fibres and of fast IIX fibres were observed in EDL, PI and diaphragm of CA rats in comparison with CTRL. In soleus of CA rats the proportion of IIA fibres was lower than in CTRL. In EDL of PF rats atrophy of IIA fibres and changes in fibre type distribution were similar to those observed in CA rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bird droppings contain endotoxin and (1-->3)-beta-D-glucan.

Samples of bird droppings were collected and the amount of endotoxin and (1-->3)-beta-D-glucan in these was determined using a specific Limulus assay. All samples contained these agents and calculations on airborne levels demonstrated that doses at risk for inflammation and allergic alveolitis were present. Endotoxin and (1-->3)-beta-D-glucan should be considered in investigations on lung disease induced by bird droppings.

Alveolitis, Extrinsic Allergic↗

T cells from atopic individuals produce IgE-inducing activity incompletely blocked by anti-interleukin-4 antibody.

We investigated peripheral blood B and T lymphocyte functions in atopic individuals. B cells were co-cultured with mutant EL4 thymoma cells in the presence of a standard T cell supernatant (T-SN) with or without exogenous interleukin (IL)-4. IgE secretion in this assay was found to be IL-4 dependent, but not significantly different for atopic patients (n = 25) vs. normal controls (n = 25). Phytohemagglutinin plus phorbol 12-myristate 13-acetate (PHA+PMA)- induced T-SN from patients or controls was tested on normal B cells in the same assay system (in the absence of exogenous IL-4). Compared to the controls, the IgE-inducing activity was significantly increased for patients with asthma or allergic rhinitis (n = 12; p less than 0.005) but not for patients with atopic dermatitis (n = 13). The difference between the asthma or allergic rhinitis vs. the atopic dermatitis groups was significant (p greater than 0.05). Since the assay was not inhibited by interferon (IFN)-gamma, this difference can not be attributed to IFN-gamma concentrations. Other T cell activities may be different between the patient groups or atopic T cells from the respiratory mucosa may recirculate more than those from the skin. In any case, the T cells rather than the B cells were found to be abnormal in atopic individuals. If atopic T cells were stimulated with PHA+PMA not as immediately but after a resting period of 48 h in culture medium alone, the IgE-inducing activity, but not the total Ig-inducing activity or the IL-2 secretion, disappeared. In addition, a mean of 37% of the IgE-inducing activity (range of 13% to 79% for five very active T-SN) was not inhibited by an anti-IL-4 antibody which neutralized exogenous IL-4, indicating a participation of factors capable of bypassing the requirement for IL-4 for the IgE response.

Antibodies, Monoclonal↗

Stress-induced modulation of antigen-presenting cell function.

The effect of two means of inducing a stress response, heat and oxygen radicals, on the ability of an HLA-DR1 B-cell line to stimulate DR1-restricted and anti-DR1 auto- and alloreactive T-cell clones has been examined. Both forms of stress enhanced the ability of B cells to stimulate auto- and alloreactive T-cell clones and to present peptide to an influenza-virus specific T-cell clone. Furthermore, the ability of the B-cell line to present whole influenza virus was augmented by heat stress. The stress-induced enhancement of T-cell responses coincided with a modest increase in the cell-surface expression of major histocompatibility class II products. This was, however, insufficient to account for the observed functional effects. In contrast to these effects, presentation of whole antigen was inhibited by the oxygen radical intermediate, hydrogen peroxide (peroxide), in a dose-dependent manner. When analysed by SDS-PAGE, it was found that whilst overall protein synthesis decreased following both types of stress, increased synthesis of heat-shock proteins (HSP), and in particular the 70,000 MW HSP, was only evident following heat stress. The absence of an increase in the synthesis of HSP 70, in the antigen-presenting cells (APC) following the uptake of UV-treated influenza virus, however, implied that HSP 70 induction was not necessary for the presentation of whole antigen. The effects of peroxide stress appeared to be qualitatively different in several respects. First, peroxide treatment did not cause the induction of any stress proteins; second, peroxide abolished the presentation of whole antigen. In addition, heat stress of APC was unable to protect from the adverse effects of peroxide treatment, in that cells treated sequentially with heat, followed by peroxide, were unable to present whole influenza virus. In order to determine the stage of antigen presentation at which peroxide was causing inhibition, APC were treated at varying time-points after pulsing with antigen. The kinetics of the peroxide effect paralleled those of aldehyde fixation. Taking these results together it would appear that peroxide interferes with some aspects of the antigen-processing pathway.

Antigen-Presenting Cells↗

Altered contractile properties of rat cardiac muscle during experimental thiamine deficiency and food deprivation.

Alterations of cardiac contractility caused by thiamine deficiency were studied on three groups of 2 month old male Wistar rats: B1, fed a thiamine deficient diet, PF pair fed, which received an amount of thiamine free diet determined on the daily consumption of B1 animals, supplemented with appropriate thiamine supply, C ad libitum fed controls. The animals were studied after 35 days of dietary treatment. Force-velocity curves were determined in right ventricle papillary muscles. Shortening velocity was significantly lower in B1 and PF than in C muscles and in B1 than in PF muscles. The ability to develop tension was not altered. Myosin ATPase activity was assayed in preparations of myofibrils and in preparations of purified myosin. Both Ca-Mg activated myofibrillar ATPase activity and Ca-activated myosin ATPase activity were significantly reduced in B1 and PF compared to C myocardium. Furthermore Ca-activated ATPase activity was lower in B1 than in PF myocardium. Myosin isoenzyme distribution was determined by pyrophosphate gel electrophoresis of purified myosin preparations. When compared to C animals both B1 and PF animals showed a myosin electrophoretic pattern shifted towards the slow isoform V3; such a shift was more pronounced in B1 animals. Information concerning excitation-contraction coupling was obtained by determining the steady state and transient force-interval relation and by recording transmembrane action potential. B1 and PF myocardium exhibited, when compared to C, a less sensitivity to a reduction of the interval of stimulation, a faster mechanical restitution, a prolonged action potential duration. Such alterations were generally more pronounced in B1 than in PF myocardium. The results support the view that in the rat cardiac contractility is deeply affected by thiamine deficiency. The alterations of cardiac contractility seem to be caused by adaptive mechanisms rather than by cardiac failure and seem to be attributable for a big part to the reduction of food supply.

Action Potentials↗

The dual effect of thyroid hormones on contractile properties of rat myocardium.

This study was designed to investigate the changes in cardiac contractile properties induced by triiodothyronine (T3) administration in adult rats. Myofibrils and myosin were isolated from ventricular muscles from euthyroid and hyperthyroid animals and enzymatically and electrophoretically characterized. The time course of the isometric response, the force velocity curve, the force interval relation were studied in papillary muscles isolated from the right ventricles of euthyroid and hyperthyroid rats. T3 administration induced significant increases in Mg2+ activated myofibrillar ATPase activity (+11.4%) and in Ca2+ activated myosin ATPase activity (+20.1%). Significant increases in shortening velocity at low and zero loads (+20.4%) were found in papillary muscles from treated animals when compared with the control muscles. These variations in enzymatic activity and shortening velocity could be related to the increase in the amount of the fast isomyosin V1, as shown by pyrophosphate gel electrophoresis. The negative force-frequency relation at steady state, typical of rat cardiac preparations, was observed in treated and control animals; its slope was, however, halved in hyperthyroid papillary muscles when compared with control ones. In accordance with this finding, the potentiating effect of a prolonged diastolic interval was significantly reduced in hyperthyroid papillary muscles. In the frame of an interpretation of the force interval relation on the basis of the excitation contraction coupling processes, these latter observations might indicate an enhanced activity of the sarcoplasmic reticulum. We conclude that thyroid hormone administration has a dual effect on cardiac contractility, on one hand regulating the synthesis of the different isomyosin and, on the other hand, stimulating the activity of the sarcoplasmic reticulum.

Adenosine Triphosphatases↗

Influence of thyroid state on mechanical restitution of rat myocardium.

The purpose of this study was to determine whether thyroid state affects the beat-to-beat regulation of contractile strength in cardiac muscle. Transmembrane action potential and isometric force were simultaneously recorded in right ventricular papillary muscles from euthyroid, hypothyroid, and hyperthyroid rats. Large thyroid state-dependent alterations in the contractile response of the muscles were not accompanied by any significant difference in the action potential. During steady-state stimulation, single test stimuli were interpolated at varying intervals. Action potential duration and peak force of the test responses were plotted against the test stimulus interval to produce electrical and mechanical restitution curves. In all muscles studied, electrical and mechanical restitution followed different time courses; over a wide range of test intervals, action potential duration and peak force of the test responses changed in opposite directions. Thyroid state profoundly affected the recovery of contractile strength, while only minor differences were found among the electrical restitution curves of the three groups of preparations. Mechanical recovery was much faster in hyperthyroid and slower in hypothyroid than in euthyroid muscles. We conclude that electrical and mechanical restitutions occur through separate processes and that the thyroid state affects only the mechanisms responsible for the contractile recovery of rat myocardium. The modifications induced by thyroid dysfunction on contractile recovery might be accounted for by an effect of thyroid state on a time-dependent recycling of calcium by the sarcoplasmic reticulum.

Action Potentials↗

Effects of LTB4 and Ca++ ionophore A23187 on the release by human alveolar macrophages of factors controlling fibroblast functions.

Cultured human alveolar macrophages from smokers with lung cancer produced spontaneously variable amounts of factors stimulating fibroblast proliferation and production of prostaglandin E2 and collagenase by fibroblasts. These biological activities belong to molecules similar or identical to interleukin 1. Exogenous leukotriene B4 added to alveolar macrophage cultures increased the production of these factors. The Ca++ ionophore A23187 was found to have similar effects. By the control of monokine production, leukotriene B4 locally released by inflammatory cells may modulate lung fibroblast functions.

Calcimycin↗

Cobalt-57 bleomycin scanning for lung cancer detection: a prospective study in thoracic surgery.

Patients displaying an abnormal chest X-ray, in some cases, cause a difficult diagnostic problem. A differential diagnosis between benign and malignant lesions is important to determine the choice of treatment i.e. whether or not to perform a thoracotomy. In a prospective study, we have examined the role of 57Co-bleomycin scanning for prethoracotomy assessment of 60 patients with a high clinical probability of lung cancer. For these patients, a sensitivity of 89%, a specificity of 84% and an accuracy of 88% were found. However, as a consequence of the six false-negative scans (two in-situ carcinomas and four stage I carcinomas), bleomycin scanning cannot be regarded as adequate for obviating thoracotomy in patients with a high clinical probability of lung cancer but a negative scan. Nevertheless, the technique is useful for the assessment of tumour size and for the detection of hilar, mediastinal and extra-thoracic metastases, with consequences for TNM staging. It has been found that the tumour dimension correlates well with the actual anatomo-pathologic size determined after surgical examination (r2 = 0.65 and p less than 0.01). Therefore, with an accuracy around 90% for the diagnosis of lung cancer, 57Co-bleomycin scanning offers a major tool for use in clinical investigation.

Adenocarcinoma↗

Single photon emission computed tomography study of human cancer: utilization of 57Co-labelled bleomycin.

The sensitivity and specificity of single photon emission tomography with 57Co-labelled bleomycin (57Co-BLM) for the detection of cancer was determined from a prospective study involving a large group of patients selected to investigate roentgenographic abnormalities. Eighty-four of the 104 patients studied had malignant disease, of whom 76 had a positive scintigram. Eighteen of the 20 patients with benign disorders had a negative scintigram. The sensitivity and specificity was therefore 90.5 and 90% respectively. For the subset of patients who underwent investigation below the diaphragm, the sensitivity was 85.7%, while for investigation above the diaphragm, it reached 95.2% (this excluded reconstructions on the bladder level, because it produced large artifacts). This study leads to the conclusion that SPECT can be used specifically to investigate unidentified X-ray abnormality and diagnose malignancy using 57Co-BLM. In addition, we propose further investigation to evaluate the usefulness of this method in staging cancer.

Aged↗