Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been a noticeable increase in the incidence of pertussis in West Germany over the last decade. Since the availability of adequate bacteriological diagnosis a much broader clinical spectrum can be attributed to infections with B. pertussis. Three patients with an unusual clinical presentation of pertussis are presented. A three month old infant presented with severe apneic spells without cough as the sole clinical symptoms of the infection. B. pertussis was isolated in the nasopharyngeal swab. A nine month old premature infant with bronchopulmonary dysplasia after long time intubation and artificial ventilation presented with apneic spells, pulmonary and cardiac decompensation and required ventilatory support. The diagnosis was suggested by a massive leucocytosis with lymphocytosis. The diagnosis on the patient was established by serologic methods. Adult contacts of this patient developed longstanding cough and clinical signs of pertussis. The diagnosis of pertussis in these persons was established by nasopharyngeal culture. The third patient with trisomy 21 and a corrected AV canal suffered from nonspecific cough and gradually developed signs of congestive heart failure with pneumonia. B. pertussis was isolated from the nasopharynx. This patient showed neither the typical paroxysmal coughing spells nor disclosed the typical lymphocytosis in his white blood count. Microbiological investigations of patients with symptoms of respiratory tract infections should include the isolation of B. pertussis. Thus, additional cases of pertussis not suspected on the basis of their initial clinical presentation will be detected.
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PMID:[Pertussis--an illness with typical clinical symptoms?]. 143 95

The functional integrity of the beta- and alpha-adrenergic stimulatory pathways in a rapid ventricular pacing model of congestive heart failure in dogs was investigated; normal dogs served as controls. Total beta-adrenergic receptor density was 35% lower (p less than 0.01) in the pacing-overdrive dogs, and the beta-adrenergic receptor-mediated stimulation of adenylate cyclase (Vmax) was found to be 68% and 72% lower (p less than 0.01) in the left and right ventricles of the paced dogs. In addition, the basal adenylate cyclase activity was found to be 56% and 68% lower (p less than 0.01) in the left and right ventricles of the failing heart. Similarly, the Vmax of 5'-guanylylimidodiphosphate (GppNHp) and forskolin stimulation of adenylate cyclase activity was significantly lower, 70% and 55%, respectively (p less than 0.01), in both ventricles of the paced dogs. However, although the concentration yielding half-maximal velocity for beta-agonist and GppNHp stimulation of adenylate cyclase was similar in both groups, that for forskolin stimulation of the enzyme was significantly increased (p less than 0.01). Pertussis toxin-mediated ADP-ribosylation of membranes from control and failing hearts revealed a significant decrease in the inhibitory guanine nucleotide binding protein content (48 +/- 9%, p less than 0.01) in the hearts of the paced dogs. Moreover, although the pertussis toxin treatment increased the basal and the forskolin-stimulated adenylate cyclase activity in both normal and failing heart membranes, the adenylate cyclase activity remained significantly depressed in the failing heart after pertussis toxin treatment (p less than 0.01). Consistent with the depressed adenylate cyclase activity, mechanical studies on isolated papillary muscles and trabeculae revealed a decrease in baseline total tension (from 7.0 +/- 0.7 to 3.8 +/- 0.4 g/mm2, p less than 0.01) and dT/dt (from 26 +/- 8 to 13 +/- 1 g/mm2/sec, p less than 0.01) in the pacing-overdrive model. Tension generation and dT/dt observed in the paced dogs in response to increasing concentrations of forskolin demonstrated a rightward shift in the dose-response curve and a decrease in maximal forskolin stimulation (p less than 0.01). Similarly, maximal tension and dT/dt in the presence of isoproterenol was significantly lower than in the normal dogs (p less than 0.01). The decrease in beta-adrenergic responsiveness was accompanied by a decrease and rightward shift in alpha 1-adrenergic responsiveness (increase in tension was 1.1 +/- 0.1 g/mm2 in paced dogs versus 2.1 +/- 0.1 g/mm2 in controls, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dysfunction of the beta- and alpha-adrenergic systems in a model of congestive heart failure. The pacing-overdrive dog. 165 Feb 96

Catecholamines (CAs) had been used for the treatment of congestive heart failure (CHF). However, since continuous administration of CAs develops tolerance in hemodynamics presumably due to desensitization of beta-adrenergic receptor (beta AR)-adenylate cyclase (AC) system, beta antagonist, instead of beta agonist, has recently been employed to treat CHF, in that it may recover beta AR-AC system. In this study, the precise mechanisms of alterations in cardiac beta AM-AC system after chronic administration of beta agonist or antagonist, were investigated. The rats were treated continuously for 14 days with saline, isoproterenol (ISO), atenolol (ATENO), or denopamine (DENO), a new positive inotropic agent with beta 1 selective AR agonistic properties, which is reported to hardly cause the tolerance in clinical studies. beta AR density (Bmax) was markedly reduced by ISO and slightly increased by ATENO. Forskolin stimulated cyclase activity was reduced markedly by ISO. Total amount of the pertussis toxin substrates (inhibitory G-protein; Gi) and cholera toxin substrates (stimulatory G-protein; Gs) were not different among 4 groups. However, Gs activity measured by human platelet reconstitutive assay was reduced by ISO and DENO. These results indicate that ISO-induced desensitization in caused by the reduction in Gs and AC-catalytic activity as well as by the down-regulation of beta AR. Furthermore, it is suggested that DENO may cause slight desensitization of beta AR-AC system due to reduced Gs activity.
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PMID:[Isoproterenol, denopamine, and atenolol-induced alterations in beta-adrenergic receptor-adenylate cyclase system of rat myocardium]. 168 39

This study was designed to assess G protein function in mononuclear leukocytes (MNL) of patients with congestive heart failure (CHF). MNL membranes were ADP-ribosylated in vitro in the presence of pertussis or cholera toxin. The amount of pertussis toxin substrates did not differ significantly between CHF patients (6,100 +/- 224 fmol/mg, n = 23) and age-matched healthy control subjects (5,812 +/- 972 fmol/mg protein, n = 19). Among the CHF patients, no differences were observed between those with idiopathic and ischemic CHF. The amount of cholera toxin substrates also did not differ significantly between CHF patients (7,522 +/- 1,405 fmol/mg protein, n = 11) and control subjects (5,654 +/- 707 fmol/mg protein, n = 14). Moreover, basal and isoproterenol- and prostaglandin E1-stimulated cyclic AMP (cAMP) accumulation in MNL was similar in control subjects and patients. To detect more subtle alterations of the cAMP-generating system, we incubated anticoagulated blood with 250-400 ng/ml pertussis toxin for 4 hours at 37 degrees C. This treatment completely ADP-ribosylated the MNL pertussis toxin substrates. Incubation with pertussis toxin did not change basal or prostaglandin E1-stimulated cAMP generation in MNL of control subjects, but it significantly enhanced stimulated generation (443 +/- 44 vs. 643 +/- 93 pmol/10(7) cells, p less than 0.025) in MNL of CHF patients. This enhancement was most pronounced in the most severely ill patients (New York Heart Association class IV) and correlated with plasma norepinephrine levels, another marker of CHF severity (r = 0.798, n = 11, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin treatment of whole blood. A novel approach to assess G protein function in congestive heart failure. 215 37

1. Patients with congestive heart failure (CHF) have an elevated activity of the sympatho-adrenal system. We have investigated several aspects of beta-adrenoceptor desensitization in such patients. 2. The positive inotropic response to isoprenaline was attenuated in CHF patients, and the pD2-values for isoprenaline's positive inotropic effect gradually decreased in more severe forms of the disease. Stimulation of adenylate cyclase by isoprenaline was also mitigated in cardiac membranes from patients with CHF. 3. We then studied the density of cardiac beta 1- and beta 2-adrenoceptors in order to understand the mechanism of beta-adrenoceptor desensitization in these patients. Our data show that cardiac beta 1-adrenoceptors are down-regulated in all forms of severe CHF, but that cardiac beta 2-adrenoceptor density decreases only in some forms of CHF including ischaemic cardiomyopathy and mitral valve disease. 4. In circulating mononuclear leucocytes (MNL) obtained from CHF patients at rest, isoprenaline- and prostaglandin E1-stimulated cAMP generation as well as cholera toxin and pertussis toxin catalyzed ADP ribosylation were similar to those in MNL from control patients. However, pretreatment of intact MNL with pertussis toxin enhanced cAMP generation in CHF patients but not in healthy control subjects, suggesting a tonic inhibitory effect of Gi in such patients. 5. We conclude that alterations of adrenoceptors and of their signal transduction might contribute to the desensitization of beta-adrenergic responses in CHF.
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PMID:Mitigation of beta 1- and/or beta 2-adrenoceptor function in human heart failure. 217 27

Patients with asthma who have incomplete control of their symptoms or require regular systemic steroidal therapy are said to have recalcitrant asthma. A systematic approach may significantly improve quality of life. Factors that should be evaluated include living with an antigen, occupational exposure, use of beta-adrenoreceptor blockers, use of nonsteroidal anti-inflammatory agents, sensitivity to dietary chemicals, endocrinopathies, gastroesophageal reflux, sinusitis, bronchopulmonary aspergillosis, and noncompliance. Other diseases may mimic asthma or exacerbate nonspecific bronchial hyperreactivity. These include congestive heart failure, chronic infectious bronchitis resulting from cystic fibrosis, ciliary dysfunction syndrome, and immunodeficiency syndromes, upper airway obstruction, pertussis syndrome, psychogenic coughs, bronchiolitis obliterans, chronic eosinophilic pneumonia, and vasculitides. A systematic approach to the evaluation of coexisting factors and potential exacerbating diseases is presented.
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PMID:Recalcitrant asthma: an allergist's approach. 229 75

Guanine nucleotide binding proteins were examined for their influence in developmental and adaptive models of adrenergic actions in the heart. In primary cultures of rat cardiac myocytes, the positive chronotropic response to the alpha-agonist, phenylephrine, changes to negative when these cells are grown with and innervated by sympathetic nerves from the paravertebral chain. Innervated cells have significantly more G protein, as determined by the ADP-ribosylation reaction catalyzed by pertussis toxin, which is linked functionally to the negative chronotropic response. Adult canine Purkinje fibers that respond to phenylephrine with a decrease in automaticity are also linked biochemically and functionally to a G protein that serves as a pertussis toxin substrate. Fibers that increase in automaticity after exposure to phenylephrine, either under control conditions (a minority of fibers) or after prior exposure to pertussis toxin (a majority of fibers), have markedly reduced levels of G. A G protein was also shown to be important in the blunted adrenergic responsiveness that characterizes congestive heart failure in human subjects. In this model, the receptor complex is beta-adrenergic and the involved G protein is a cholera toxin substrate. Gs is reduced in the lymphocytes of patients with congestive heart failure and increases toward normal after successful therapy. These observations highlight the important roles that G proteins have in adrenergic actions of the heart both with respect developmental and adaptive changes.
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PMID:G protein-adrenergic interactions in the heart. 284 13

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

In order to explain the attenuated sympathetic support during the development of heart failure, the status of beta-adrenergic mechanisms in the failing myocardium was assessed by employing cardiomyopathic hamsters (155-170 days old) at moderate degree of congestive heart failure. The norepinephrine turnover rate was increased but the norepinephrine content was decreased in cardiomyopathic hearts. The number and the affinity of beta receptors in the sarcolemmal preparations were not changed in these hearts at moderate stage of congestive heart failure. While the basal adenylyl cyclase activity was not altered in sarcolemma, the stimulation of enzyme activity by NaF, forskolin, Gpp(NH)p or epinephrine was depressed in hearts from these cardiomyopathic hamsters. Since G-proteins are involved in modifying the adenylyl cyclase activity, the functional and bioactivities as well as contents of both Gs and Gi proteins were determined in the cardiomyopathic heart sarcolemma. The functional stimulation of adenylyl cyclase by cholera toxin, which activates Gs proteins, was markedly depressed whereas that by Pertussis toxin, which inhibits Gi proteins, was markedly augmented in cardiomyopathic hearts. The cholera toxin and pertussis toxin catalyzed ADP-ribosylation was increased by 37 and 126%, respectively; this indicated increased bioactivities of both Gs and Gi proteins in experimental preparations. The immunoblot analysis suggested 74 and 124% increase in Gs and Gi contents in failing hearts, respectively. These results suggest that depressed adenylyl cyclase activation in cardiomyopathic hamsters may not only be due to increased content and bioactivity of Gi proteins but the functional uncoupling of Gs proteins from the adenylyl cyclase enzyme may also be involved at this stage of heart failure.
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PMID:Alterations in G-proteins in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters. 789 87

Experiments were designed to determine whether a heterogeneity of endothelium-dependent relaxations in arteries from different vascular beds exists in experimental congestive heart failure (CHF) and to determine the mediators of those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d. Rings of coronary, femoral, and renal arteries with and without endothelium from control and CHF dogs were suspended in organ chambers for measurement of isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium-dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9% vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal arteries. Relaxations to adenosine diphosphate and the calcium ionophore were unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that endothelium-dependent relaxations are affected heterogeneously in CHF. The enhanced response to alpha 2-adrenergic agonists in the coronary artery is mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis toxin. This selective increase in endothelium-dependent relaxations in the coronary artery may contribute to preserving coronary blood flow during CHF.
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PMID:Increased production of nitric oxide in coronary arteries during congestive heart failure. 828 83


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