[Recurrent oral aphthosis: treatment with pentoxifylline].
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Humans↗
Biomedical subjects
M Ferrer
Publications and source records attributed to M Ferrer.
Prenatal diagnosis of exencephaly.
This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post-partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly.
Adult↗
Phorbol dibutyrate induces contractions in bovine cerebral arteries by an extracellular calcium-independent mechanism.
The aim of the present study was to analyse the ability of phorbol 12,13-dibutyrate (PDB) to activate protein kinase C (PKC), measured by its capacity to translocate the enzyme from the cytosol to the membrane fraction, as well as to induce vasconstrictive responses in segments from branches of bovine cerebral arteries. PDB (0.1 microM) produced a marked translocation of PKC activity from the cytosolic to the membranous fraction. This drug induced concentration-dependent contractions which were slow in onset. The contraction elicited by PDB was reduced by the PKC inhibitor, staurosporine (1 and 10 nM), but unaltered by both Ca(2+)-free medium containing 3 mM EGTA and the Ca(2+)-channel antagonist, nifedipine (1 microM). Preincubation of segments with PDB (10 and 30 nM) reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT) in a concentration- and preincubation time-dependent manner. These data indicate that bovine cerebral arteries possess cytosolic and membranous PKC activities, that the vasoconstrictive responses induced by PDB were independent of extracellular Ca2+, that cytosolic C-kinase is translocated to the membrane and probably down-regulated by PDB, and that this enzyme is not involved in 5-HT responses, but is down-regulated by PDB.
Alkaloids↗
Specificity of endotracheal aspiration, protected specimen brush, and bronchoalveolar lavage in mechanically ventilated patients.
The specificity of the different techniques used to diagnose ventilator-associated pneumonia is still a matter of controversy. To investigate the specificity of endotracheal aspiration (EA), protected specimen brush (PSB), and bronchoalveolar lavage (BAL) quantitative cultures, we studied 27 consecutive mechanically ventilated (MV) patients (> 72 h) without clinical or radiographic evidence of pulmonary infection. Comparing different thresholds for quantitative cultures (from 10(3) through 10(6) CFU/ml), the lowest rate of false positive results was obtained using 10(6) for EA, 10(5) for PSB, and 10(6) for BAL. Using 10(6) CFU/ml for EA, 10(4) CFU/ml for PSB, and 10(5) CFU/ml for BAL as cutoff points, we obtained the following specificities: 85, 85, and 78% for the three techniques, respectively. A bacterial index of 8 was the best threshold to get a low percentage of false positive results for all techniques except for EA (0% for PSB and 12% for BAL). There were reasonable qualitative agreements (PSB versus EA = 58%; BAL versus EA = 69%; and PSB versus BAL = 62%) and poor quantitative correlations between concomitantly isolated microorganisms from the three types of samples. Quantitative cultures of EA, PSB, and BAL may show a considerable percentage of false positive results at the respective cutoff points usually accepted. Increasing the thresholds for quantitative cultures, albeit loosing sensitivity, may rule out better the absence of pulmonary infection in MV patients.
Bacteria↗
Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation.
We studied the interrelations between gastric, pharyngeal, proximal, and distal airway bacterial flora in ventilator-associated pneumonia (VAP) on 36 patients with nosocomial pneumonia acquired during mechanical ventilation (MV) and 27 mechanically ventilated control subjects without pulmonary infection. Gastric, pharyngeal, and endotracheal (EA) sampling for quantitative cultures were performed upon all patients, as well as fiberoptic bronchoscopy with protected specimen brush (PSB) sampling. Mean bacterial and fungi colony counts were significantly increased in pharyngeal, EA, and PSB samples in patients with VAP compared with control subjects. The overall increase in colonization was due to gram-positive cocci in all samples. In addition, gram-negative bacilli and fungi mean counts increased significantly in PSB pneumonia samples versus control samples. However, mean gastric colonization was similar in both patients with VAP and control subjects. In the former group there was an increase in coincident microorganisms isolated from gastric, pharyngeal, and EA samples in relation to PSB samples compared with control samples. Among the different quantitative cultures analyzed, only those obtained from EA significantly correlated with PSB cultures in patients with pneumonia (r = 0.67, p = 0.001). In summary, the present study shows that the coincidence between microorganisms isolated in PSB cultures and those from gastric and oropharynx increase in MV patients with pneumonia, indicating that both reservoirs play a key role in the pathogenesis of pneumonia. Conceivably, preventing both gastric and pharyngeal colonization may reduce the incidence of ventilator-associated pneumonia. From all the noninvasive samples studied only endotracheal aspirate cultures were useful for inferring the etiology of some VAP pneumonias.
Bacteria↗
Quantitative cultures of endotracheal aspirates for the diagnosis of ventilator-associated pneumonia.
Bronchoalveolar lavage (BAL) and protected specimen brushing (PSB) are the most commonly used methods for diagnosing ventilator-associated (VA) pneumonia although they require bronchoscopy. Endotracheal aspiration (EA) is a simple and less costly technique than PSB or BAL. The purpose of our study was to investigate the diagnostic value of EA quantitative cultures and to compare the results obtained using EA with those obtained using PSB and BAL in mechanically ventilated patients with or without pneumonia. We prospectively studied 102 intubated patients divided into three diagnostic categories: Group I (definite pneumonia, n = 26), Group II (uncertain status, n = 48), and Group III (control group, n = 28). All patients received prior antibiotic treatment. EA, PSB, and BAL were obtained sequentially in all patients. When comparing Group I with Group III and using 10(5) cfu/ml as a threshold, we found that EA quantitative cultures represented a relatively sensitive (70%) and relatively specific (72%) method to diagnose VA pneumonia. The specificity of BAL and PSB (87% and 93%, respectively) was better than that of EA. The negative predictive value of EA cultures was higher (72%) when compared with that obtained using PSB (34%) (p < 0.05). EA quantitative cultures correlated with PSB and BAL quantitative cultures in patients with definite pneumonia. Although EA quantitative cultures are less specific than PSB and BAL for diagnosing VA pneumonia, our results suggest that the former approach may be used to treat these patients when bronchoscopic procedures are not available.
Bacteria↗
Both the alpha and beta chains of high-affinity interleukin 2 receptors are located in intracellular vesicles when their ligand is endocytosed.
The growth factor interleukin 2 (IL2) binds to high and low-affinity receptors (Kd approximately 10-100 pM and 10 nM, respectively) present on activated T lymphocytes. High-affinity receptors are composed of two non-convalently linked polypeptides, alpha and beta of 55 and 70 kDa. These two polypeptides do not share any sequence homology, but each of them, in the absence of the other, binds IL2: alpha with a Kd approximately 10 nM and beta with a Kd approximately 1 nM. When these two chains are associated in lymphocytes, they form high-affinity receptors that mediate IL2 endocytosis and degradation, and transduce IL2 signaling. On cells that physiologically express IL2 receptors, such as activated T lymphocytes, both high and low affinity-receptors are present simultaneously on the cell surface, and low-affinity receptors (alpha without beta) are, in most instances, more abundant by a factor 5 to 10 than high-affinity receptors (alpha associated to beta). Low-affinity receptors bind IL2 but do not induce its internalization and signaling. The physiological role of the complexity of this receptor system is not fully understood. In the present study, we have investigated directly the fate of the high-affinity receptors when the ligand is endocytosed. By confocal microscopy, using two monoclonal antibodies specific for alpha and for beta, respectively, we show that each of these two polypeptides is located in intracellular endocytic compartments. Therefore, when the alpha chain is part of high-affinity receptors, it is endocytosed, as opposed to when it is part of low-affinity receptors and is not endocytosed.(ABSTRACT TRUNCATED AT 250 WORDS)
Brefeldin A↗
Effectiveness of morphine in non-cardiogenic pulmonary edema due to chlorine gas inhalation.
We report the case of an 11-yr-old boy who developed a non-cardiogenic pulmonary edema following inhalation of chlorine gas at a swimming pool. Rapid clinical improvement was noted after i.v. administration of morphine.
Child↗
Comparison of the vasoconstrictor responses induced by endothelin and phorbol 12,13-dibutyrate in bovine cerebral arteries.
The vascular effects of endothelin-1 (ET-1) were compared with those elicited by phorbol 12,13-dibutyrate (PDB), an activator of the protein kinase C (PKC), to analyze the involvement of this enzyme on ET-1 responses. PDB and ET-1 caused slow-developing contractions (sustained and transient, respectively), which were reduced by the PKC inhibitor, staurosporine (1 and 10 nM). Only the contractile effects evoked by ET-1 were reduced in Ca-free medium and by the Ca channel antagonist, nifedipine (1 microM), and increased by the Ca channel agonist, BAY K 8644 (10 nM). PDB (10 and 30 nM) preincubation reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT; 0.01, 0.1 and 1 microM) in a way dependent on phorbol concentration and preincubation time, whereas ET-1 (1 nM) increased the contractile response to 5-HT (0.1 microM). Furthermore, PDB (0.1 microM) also reduced the responses elicited by ET-1 (30 microM) and vice versa. ET-1 (0.1 microM) induced transient translocation of PKC activity from the cytosol to the membrane, which was less than that produced by PDB (0.1 microM). Electrical stimulation induced [3H]noradrenaline (NA) release, which was increased by PDB (10 and 100 nM) and not affected by ET-1 (10 nM). These results indicate: (1) the responses induced by PDB and ET-1 were independent and dependent on extracellular Ca, respectively; (2) PKC is involved in NA release and 5-HT responses, but mainly in desensitization of these responses, and (3) PKC is activated by ET-1 and is implicated in vascular actions of ET-1, but other mechanisms, such as the activation of ET-1 receptors and opening of dihydropyridine-sensitive Ca channels also appear to be involved.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
High-affinity interleukin 2 receptor alpha and beta chains are internalized and remain associated inside the cells after interleukin 2 endocytosis.
High-affinity interleukin 2 (IL2) receptors on human T lymphocytes are multimeric complexes containing two IL2-binding polypeptides, alpha and beta chains of 50-55 and 70-75 kDa, respectively, associated by noncovalent bonds. IL2 binds to high-affinity IL2 receptors on the surface of T lymphocytes, mediates cell growth, and is internalized. In this paper, we used a biochemical method to directly identify the receptors components internalized together with the ligand. 125I-IL2-receptor complexes were solubilized with the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate, and IL2-binding polypeptides were identified by cross-linking with disuccinimidyl suberate. Under such conditions, the noncovalent association between alpha and beta is maintained. After IL2 internalization, two complexes of about 70 and 90 kDa, IL2 crosslinked to alpha and beta, respectively, were found inside the cells. Both components were immunoprecipitated with either anti-alpha or anti-beta monoclonal antibodies. This shows that the alpha and beta chains are found in an intracellular compartment after IL2 endocytosis, and remain associated as a ternary complex with IL2.
Cholic Acids↗
Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation.
We previously demonstrated that long term treatment of the Ag-specific CD4+ T cell clone P28D with soluble HIV envelope glycoprotein gp120 results in a marked impairment of CD3/TCR-mediated responses. In this report, to further understand these inhibitory effects, the binding properties and internalization of gp120 have been investigated, in parallel with functional studies, in long term incubations of P28D cells with gp120. Immunofluorescence studies show that surface-bound gp120 level is maximal within 1 h of incubation at 37 degrees C and then gradually decreases. This decrease is accompanied by a progressive down-modulation of membrane CD4 (30-35% loss over a 18-h incubation period) without concomitant alteration of the CD4 mRNA steady-state level. Similar experiments performed with 125I-labeled gp120 demonstrate that the glycoprotein is progressively internalized (up to 35% internalized material after 18 h) and that it accumulates inside the cells. Confocal microscopy studies show that internalized gp120 is concentrated in localized intracellular compartments. CD4 also accumulates in compartments with a similar localization and is stained with mAb OKT4 but not with mAb OKT4a. Concomitantly to internalization of gp120 and disappearance of membrane CD4, a correlated loss of the CD4-associated tyrosine kinase p56lck is evidenced. Interestingly, a progressive impairment of the P28D responses to specific Ag or to anti-CD3 mAb is also observed. Inhibitions of T cell proliferation increase with the degree of both CD4 and p56lck down-modulation. Removal of exogenous gp120 results in a rapid and spontaneous release of internalized gp120 into a degraded form. A progressive restoration of CD4 and p56lck levels is also noticed. In parallel, CD3/TCR-mediated responses of clone P28D are fully recovered. Altogether, our results suggest that HIV-1 glycoprotein gp120 is able to down-modulate membrane CD4 presumably by a cointernalization process and to further down-modulate the associated p56lck. This dual phenomenon is presumably involved in the direct immunosuppressive effect of gp120 on the CD3/TCR-mediated activation pathway.
Antigens, Differentiation, T-Lymphocyte↗
The lymphocyte-specific tyrosine protein kinase p56lck is endocytosed in Jurkat cells stimulated via CD2.
Incubation of the human T cells, Jurkat, with two sets of activating anti-CD2 mAb (T11(2) + T11(3), D66 + T11(1)) induced delocalization of p56lck and CD2 receptors from the plasma membrane and increased the tyrosine kinase activity of p56lck. The anti-CD2 mAb combination (T11(2) + T11(3)) that produced the most rapid increase in p56lck kinase activity also induced the most rapid delocalization of the kinase. In stimulated cells, both p56lck and CD2 receptors are detected in cytoplasmic vesicles. The internalization of p56lck in endocytic vesicles was established by confocal microscopy. By double staining it was shown that only part of the p56lck colocalized with the internalized CD2 receptor suggesting distinct sorting processes. Internalization of p56lck appeared to be specific of CD2 stimulation as: 1) in Jurkat cells triggered with an anti-CD3 mAb, p56lck was not internalized whereas CD3 receptors were completely endocytosed; 2) when cells were stimulated via CD4, the kinase and CD4 receptors remained associated with the plasma membrane. In addition, internalization of p56lck upon stimulation of CD2 receptors was not modified in CD2+/CD3-Jurkat cells indicating that CD3 is not involved in this process. The identification of different subcellular localizations of p56lck in resting and stimulated T cells should represent an important step in the definition of its functional activity.
Antigens, Differentiation, T-Lymphocyte↗
Presynaptic muscarinic receptor subtypes involved in the inhibition of acetylcholine and noradrenaline release in bovine cerebral arteries.
Experiments were performed in bovine cerebral arteries preincubated with [3H]-choline or [3H]-noradrenaline to analyze the presynaptic muscarinic receptors involved in inhibition of acetylcholine and noradrenaline release induced by electrical stimulation (4 Hz, 200 mA, 0.3 ms, 1 min). For this purpose, the actions of several muscarinic receptor antagonists on the 3H overflow and on the carbachol-induced inhibition of this overflow were assessed. The evoked [3H]-acetylcholine release and [3H]-noradrenaline release were markedly reduced by the presence of tetrodotoxin, Ca(2+)-free medium, and the inhibitor of both choline transport and choline acetyltransferase, AF64A. Chemical sympathetic denervation with 6-hydroxydopamine (6-OHDA) decreased the uptake of [3H]-noradrenaline, and AF64A reduced mainly the uptake of [3H]-choline, but also of [3H]-noradrenaline. Carbachol reduced the evoked [3H]-noradrenaline and [3H]-acetylcholine release; the IC50 values were 0.37 and 0.43 mumol/l, respectively. Atropine and 4-DAMP, but not AF-DX 116, methoctramine or pirenzepine, increased the evoked [3H]-acetylcholine release. However, these muscarinic antagonists failed to modify the evoked [3H]-noradrenaline release. Carbachol inhibited the release of both acetylcholine and noradrenaline. The inhibition was blocked by the antagonists. The rank orders of potency (based on plC50 values) were, in the case of [3H]-acetylcholine release, atropine greater than 4-DAMP greater than AF-DX 116 greater than or equal to pirenzepine greater than or equal to methoctramine, and, in the case of [3H]-noradrenaline release, atropine greater than 4-DAMP greater than AF-DX 116 greater than or equal to methoctramine greater than or equal to pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Vasoconstrictive responses elicited by endothelin in bovine cerebral arteries.
1. Endothelin (ET-1) induced concentration-dependent contractions, which were slowly developed in segments of bovine cerebral arteries. Furthermore, this agent produced tachyphylaxis. 2. The contractions evoked by ET-1 were markedly reduced in Ca-free medium containing 1 mM EGTA and by the Ca channel antagonist, nifedipine (1 microM), but increased by the Ca channel agonist, BAY K 8644 (10 nM). 3. The contractions caused by ET-1 were significantly reduced by the protein kinase C (PKC) inhibitor, staurosporine (1 and 10 nM). 4. These results indicate that ET-1 induced potent vasoconstrictive responses, probably mediated by PKC activation, which were mainly dependent on extracellular Ca; this Ca enters the smooth muscle cells via dihydropyridine sensitive Ca channels.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Vasoconstrictive effects of angiotensin I and II in cat femoral arteries. Role of endothelium.
1. AI and AII induced concentration-dependent contractions in cat femoral artery segments, the potency of AII being greater than that of AI. 2. The antagonist of AII receptors, saralasin (1 and 10 nM), inhibited the AI and AII responses. 3. Indomethacin (10 microM) and endothelium removal increased the responses to AII, whereas those induced by AI were barely affected. 4. The response induced by AI was reduced by captopril (200 microM). 5. These data suggest: (1) the contractions induced by AII are mediated by AII receptors and endothelial products derived from cyclooxygenase, (2) the response to AI is, in part, produced by its conversion into AII.
Angiotensin I↗
Diagnostic value of telescoping plugged catheters in HIV-infected patients with pulmonary infiltrates.
To assess the diagnostic value of telescoping plugged catheters (TPC) in human immunodeficiency virus (HIV)-infected patients with pulmonary infiltrates (PI), we performed a prospective clinical study in 71 episodes of fever and PI in 66 HIV-infected patients (five patients had two different episodes of fever and PI). A control group of 12 HIV-infected patients with fever and normal chest roentgenogram was also studied. In all patients and prior to antibiotic treatment (except in mechanically ventilated patients), a TPC using quantitative cultures (cutoff point established at 10(3) CFU/ml) and a bronchoalveolar lavage (BAL) sampling were performed via fiberoptic bronchoscope. The overall incidence of bacterial pneumonia in the study group was 21 percent. The TPC cultures resulted in a microbiologic diagnosis of bacterial pneumonia in eight patients (11 percent) from the study group and in one patient (8 percent) from the control group. The TPC sensitivity in diagnosing bacterial infections was 53 percent and specificity was 76 percent. Negative predictive value was 85 percent and positive predictive value was 38 percent. By means of BAL, 35 episodes from the study group and two from the control group were diagnosed as nonbacterial or mycobacterial pulmonary infections. Considering TPC and BAL together, diagnosis was performed in 42 cases of PI (59 percent). Twenty percent (17/83) of HIV-infected patients suffered from bacterial colonization of their lower airways (a TPC culture greater than or equal to 10(3) CFU/ml without clinical evidence of bacterial infection). We conclude that the combined use of TPC and BAL may be useful in HIV-infected patients with PI, since this combined use allows the proper diagnosis of bacterial and nonbacterial infections, thereby increasing the overall diagnostic accuracy. To distinguish bacterial colonization from pulmonary infection in HIV-infected patients with PI, the cutoff point of quantitative cultures of TPC may be 10(4) CFU/ml.
Adult↗
Modulation of interleukin 2 internalization and interleukin 2-dependent cell growth by antireceptor antibodies.
The growth factor interleukin 2 (IL2) binds to and is internalized together with high-affinity surface receptors present on lymphoid cells. This endocytosis thus results in down-regulation of the receptors. However, it is not known if the internalization is relevant to the induction of cell growth. In the present study a rat monoclonal antibody to the P55 chain of the IL2 receptor was used to examine the role of receptor internalization in the IL2-dependent autocrine human tumor T cell line IARC 301. When given alone, this antibody did not inhibit IL2 binding, internalization, or IL2-dependent cell proliferation. However, crosslinking by anti-rat immunoglobulins, which did not affect binding of the growth factor, inhibited both IL2 internalization and cell proliferation. Besides offering a novel means for the specific inhibition of the uptake of IL2 bound to IL2 high-affinity receptors, the results are compatible with the association of this receptor-ligand uptake to the growth stimulation by IL2.
Antibodies, Monoclonal↗
Evaluation of the available invasive and non-invasive techniques for diagnosing nosocomial pneumonias in mechanically ventilated patients.
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Animals↗