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Biomedical subjects

M Delos

Publications and source records attributed to M Delos.

At least 37 records · Page 2Linked to original sources

Upregulation of urokinase in alveolar macrophages and lung tissue in response to silica particles.

Impaired fibrinolytic activity and persistent fibrin deposits in lung tissue have been associated with lung fibrotic disorders. The present study examined the sources of plaminogen activator (PA) changes induced by a single intratracheal administration of silica particles (5 mg) in the mouse lung. We found in both control and silica-treated animals that amiloride almost totally abolished PA activity in bronchoalveolar lavage (BAL) fluid (BALF), indicating that initial upregulation (from day 1) as well as sustained PA activity (up to day 30) observed in response to silica is related to changes in urokinase-type PA (uPA). The upregulation of BALF uPA activity was associated with a marked and persistent increase in uPA mRNA levels in lung tissue. Changes in uPA expression were also reflected in the BAL cell fraction. A maximal and constant increase in cell uPA activity was associated with the early response to silica, whereas significant but lower upregulation was still noted at the fibrotic stage. From days 3 to 30, a progressive increase in uPA mRNA levels was noted in BAL inflammatory cells elicited by silica. Because the number of BAL neutrophils was strongly correlated with BALF and BAL cell-associated uPA activity, their involvement in uPA upregulation was addressed by inducing neutropenia with cyclophosphamide (200 mg/kg ip) before administration of the silica. Neutrophilic depletion did not, however, reduce, and even increased, the BAL cell-associated uPA activity. At the BALF level, neutropenia did not change PA activity in silica-treated mice, pointing to alveolar macrophages as the principal source of uPA in response to silica. Immunohistochemical stainings identified alveolar macrophages and pneumocytes as uPA-expressing cells in silica-treated animals (day 30). Intense and heterogenous staining was observed in silicotic nodules. These findings indicate that urokinase produced by alveolar macrophages is operative not only at the alveolitis stage but also later in the fibrotic process, produced by silica particles, supporting the role of uPA in fibrogenesis.

Amiloride↗

Role of urokinase in the fibrogenic response of the lung to mineral particles.

The lung plasminogen activator (PA) response was examined in four different models of particle-induced pulmonary lesions in NMRI mice (single intratracheal administration, 0.75 to 5 mg/mouse). Sequential changes in cellular (total and differential counts) and biochemical markers of alveolitis (lactate dehydrogenase [LDH], total proteins) were monitored in bronchoalveolar fluid (BALF) and the fibrotic lung response was assessed histologically. An intense but spontaneously resolving alveolitis was produced by manganese dioxide (MnO2) and a fibrosing alveolitis was elicited by crystalline silica (DQ12). Minimal and noninflammatory responses were obtained after instillation of titanium dioxide (TiO2) and tungsten carbide (WC), respectively. The comparison between the resolving and the fibrosing alveolitis model was especially taken into consideration in an attempt to identify fibrinolytic changes associated with the development of fibrosis. At the alveolitis stage, similarly increased BALF PA activities were measured in both the resolving and the fibrosing alveolitis models whereas only slight and no PA modifications were noted after administration of TiO2 and WC, respectively. Persistently (up to 120 d) increased BALF PA activity was selectively associated with the progression to fibrosis (DQ12), suggesting that PA is involved in the fibrotic process. ELISA measurements demonstrated that the changes in BALF PA activity were exclusively related to changes in urokinase (uPA), not tissue-type PA. A rapid and persisting (up to Day 30) upregulation of cell-associated PA activity occurred after DQ12, MnO2, and TiO2 treatment only. Cellular PA activity was however significantly higher in fibrogenic inflammatory cells recovered from DQ12 than from MnO2-treated mice suggesting that the intensity of cellular PA upregulation may represent an early indicator of the progression to fibrosis. The implication of urokinase in the pathogenesis of silica-induced fibrosis was demonstrated by the use of a uPA knockout mice. The acceleration of the fibrotic process in uPA-deficient compared with the wild type animals demonstrated the contribution of uPA to limit the fibrotic process.

Animals↗

Granulomatous bronchiolitis associated with Crohn's disease.

Symptomatic bronchopulmonary disorders have been only occasionally reported in Crohn's disease, although several studies have documented the possibility of latent involvement of the respiratory tract. We report the case of a patient with long-standing Crohn's disease who presented with acute transient chest pain and a recent history of mild dyspnea and nonproductive cough. Chest radiographs were normal, while high-resolution computed tomography demonstrated a mosaic pattern of attenuation that was consistent with a bronchiolar disorder. Pulmonary function tests showed mild airway obstruction and normal diffusion indices. Thoracoscopic lung biopsy demonstrated focal infiltration of the bronchiolar walls by mononuclear cells and non-necrotizing granulomas. To our knowledge, this is the first account of isolated granulomatous bronchiolitis in Crohn's disease. These findings suggest that a granulomatous inflammatory process of the bronchioles could be involved in the development of airway obstruction in patients with Crohn's disease.

Adult↗

Role of interleukin-10 in the lung response to silica in mice.

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.

Animals↗

Secretory component production by human bronchial epithelial cells is upregulated by interferon gamma.

Secretory immunoglobulin A (S-IgA) participates in the first noninflammatory line of defence of the respiratory tract. S-IgA consists of dimeric IgA (dIgA) produced by plasma cells and secretory component (SC) produced by epithelial cells. This study compared SC production by primary cultures of human bronchial epithelial cells (HBEC) and by respiratory epithelial cell lines. Among the cell lines, A549 did not produce detectable SC, 16HBE produced very low levels of SC, while CALU-3 produced significant levels of SC. HBEC produced SC in nonpolarized and polarized primary cultures, where it was secreted apically. Polarized HBEC transcytosed radiolabelled and cold dIgA, resulting in the presence of S-IgA in their apical media. SC production and IgA transcytosis by polarized HBEC were upregulated by interferon-gamma (IFN-gamma) after 48 h. By reverse transcription-polymerase chain reaction, no SC messenger ribonucleic acid (mRNA) was detected in A549 and 16HBE, while SC mRNA in CALU-3 was comparable to that of HBEC incubated for 48 h with IFN-gamma. By immunocytochemistry, HBEC expressed SC immunostaining and its intensity increased after 48 h with IFN-gamma. It is concluded that human bronchial epithelial cells produce secretory component and transcytose dimeric immunoglobulin A in vitro. These processes were apically polarized and upregulated by interferon-gamma. Among the cell lines studied, only CALU-3 expressed secretory component-messenger ribonucleic acid and produced detectable secretory component.

Aged↗

External auditory canal cholesteatoma.

A cholesteatoma originating in the external auditory canal is a rare finding. We report 2 cases illustrating its typical localization in the inferior part of the auditory canal and its marked osteolytic character. The extension of such a cholesteatoma in the depth of the temporal bone is often larger than suggested by clinical examination. Since the purpose of treatment is to achieve the complete eradication of the epidermic matrix, surgical treatment is required in most cases. We discuss herein the follow-up strategies, keeping in mind that local recurrence and bilateral disease are not uncommon.

Adult↗

CO2 laser in the diagnosis and treatment of early cancer of the vocal fold.

A total of 74 patients underwent cordectomy using CO2 laser for either diagnosis or treatment of an early cancer of the vocal fold. Type I cordectomy consisted in the resection of the entire epithelium, while leaving the vocal ligament intact. Type II cordectomy involved removal of the vocal fold from the vocal process to the anterior commissure and passing through the inferior thyroarytenoid muscle. Type IIIA required vocal fold resection along the internal side of the thyroid ala, while type IIIB included removal of the anterior commissure. Type I cordectomies were carried out with an Acuspot micromanipulator, which provided a 250-micron-diameter beam for a working distance of 400 mm, and in the shot-by-shot cutting mode with 3 W power superpulse. This cordectomy was carried out in 39 patients and a dysplasia or an early carcinoma were detected in 45.9% of cases. Type II and type III procedures were performed with the Microslad micromanipulator having a 700-micron-diameter beam in the continuous cutting mode, 7 W power superpulse. Fifteen cases were treated by type II cordectomy, of which 3 T1aN0M0 cases underwent postoperative radiotherapy due to insufficient resections and 2 cases with T1bN0M0 tumors later underwent reconstructive laryngectomy. A type III cordectomy was used for 14 cases of T1aN0M0 carcinomas and 3 cases of severe dysplasia. The margins of resection were found to be positive histologically in 23.5% of these cases, making frozen section examinations mandatory at time of surgery. Results of all procedures showed that voice was best after a type I cordectomy where only the epithelium was resected. In the type II and type III cordectomies, the quality of voice depended on the development of a fibrous fold and the absence of anterior synechia in the healed larynx.

Adult↗

Expression of E-cadherin adhesion molecule in vocal cord carcinomas.

E-cadherin is a 120 kDa transmembrane protein that plays a major role in the maintenance of cell-cell adhesion in epithelial tissues. In the present study its expression was examined immunohistochemically for the first time using paraffin-embedded archival tissues of 38 vocal cord carcinomas. Ten cases of vocal cord polyps were used as positive controls. According to our criteria, results showed that all but one of the polyps, in which staining was lost, had strong or moderate E-cadherin expression, whereas 32% of the cases with tumors showed preserved staining, and 68% of cases showed a reduced staining. E-cadherin expression was significantly correlated with histological stages, with a greater expression in carcinoma in situ and microinvasive carcinoma than in invasive carcinoma (P = 0.010). A significant correlation was also found between E-cadherin expression and the degree of tumor differentiation (P = 0.018). Some of these findings were consistent with previously published data using fresh tissues. Our study provides evidence that E-cadherin may be linked to progression and differentiation of laryngeal cancer and could play a role as a tumor-suppressor gene in this cancer.

Cadherins↗

Influence of the route of administration and the chemical form (MnCl2, MnO2) on the absorption and cerebral distribution of manganese in rats.

The absorption and cerebral distribution of manganese (Mn) have been studied with respect to the route of administration and the chemical form of the Mn compound. Different groups of adult male rats received either MnCl2, 4H2O or MnO2 once a week for 4 weeks at a dose of 24.3 mg Mn/kg body wt. (b.w.) by oral gavage (g.) or 1.22 mg Mn/kg b.w. by intraperitoneal injection (i.p.) or intratracheal instillation (i.t.). Control rats were treated with 0.9% saline. Four days after the last administration the rats were killed and the concentration of Mn measured in blood, hepatic and cerebral tissues (cortex, cerebellum, and striatum). The liver Mn concentration was not affected by the treatments whatever the chemical form or the route of administration of the Mn compound. Administration of MnCl2 by g., i.p., and i.t. routes produced equivalent steady-state blood Mn concentrations (about 1000 ng Mn/100 ml), representing increases of 68, 59, and 68% compared with controls, respectively. Mn concentrations were significantly increased in the cortex but to a lesser extent (g., 22%; i.p., 36%; i.t., 48%) and were higher in the cerebellum after i.p. and i.t. administrations than after oral gavage. Rats treated i.t. with MnCl2 showed an elective increase of the striatal Mn concentration (205%). In contrast, MnO2 given orally did not significantly increase blood and cerebral tissue Mn concentrations; the low bioavailability is most likely due to the lack of intestinal resorption. Administration of MnO2 i.p. and i.t., however, led to significant increases of Mn concentrations in blood and cerebral tissues. These increments were not significantly different from those measured after MnCl2 administration, except for striatal Mn after i.t. which was markedly less (48%) after MnO2 administration. A comparison of the blood Mn kinetics immediately after g. and i.t. treatment with MnCl2 or MnO2 indicated that the higher elevation of blood Mn concentration (> 2000 ng Mn/100 ml) after i.t. administration of MnCl2 could account for the elective uptake of Mn in the striatum observed in repeated dosing experiments. It is concluded that the modulation of Mn distribution in brain regions according to the route of administration and the chemical form of the Mn compound may be explained on the basis of different blood Mn kinetics and regional anatomic specificities of the striatal region.

Animals↗

Unifocal cervical Castleman disease in two children.

UNLABELLED: Castleman disease (CD) is a benign lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes. Most observations focus on adult patients. In children the disease is rare, usually localized and may be symptomatic or asymptomatic. We reported two children, 7 and 14 years old respectively, affected by unifocal cervical CD of the hyaline vascular type. CONCLUSION: Two cases illustrate that CD may mimic a neoplasm and should be considered in presence of a solitary neck mass with specific features on CT and MRI.

Adolescent↗

Detection of reperfused ischemia of the rat intestine: value of magnetic resonance imaging with small-molecular-weight dysprosium and gadolinium chelates.

RATIONALE AND OBJECTIVES: The authors assessed whether the small-molecular-weight magnetic resonance (MR) imaging contrast agents dysprosium diethylenetriamepentaacetic acid bismethylamide (sprodiamide injection), which enhances T2*, and gadolinium diethylenetriamepentaacetic acid bismethylamide (gadodiamide injection), which enhances T1, could improve the detection of reperfused ischemia of the rat intestine. METHODS: Eighteen rats were subjected to vascular occlusion of the distal ileum for 30 minutes, followed by reperfusion. Ten minutes after reperfusion, T1- and T2-weighted spin-echo (SE) images were obtained before and after administration of sprodiamide, gadodiamide, or both. The same imaging protocol was applied in another group of 18 rats subjected to 10 minutes of occlusion and reperfusion. Histologic examination of the intestine was performed after MR imaging. RESULTS: Villous injury (ie, denudation) was observed in most cases after 30 minutes of occlusion, but not after 10 minutes of occlusion. After 30 minutes of occlusion, the superficial part of the ischemic intestine was hyperintense to the normal intestine on unenhanced T2-weighted images. Administration of sprodiamide improved the contrast between the normal and ischemic intestine on T2-weighted images, and administration of both gadodiamide and sprodiamide improved the contrast on T1- and T2-weighted images. After 10 minutes of occlusion, no contrast was discernible before or after contrast material administration. CONCLUSION: These results suggest that the detection of reperfused intestinal ischemia of sufficient duration to cause villous injury can be improved by using sprodiamide injection alone or in combination with gadodiamide.

Animals↗

Evaluation of proliferating cell nuclear antigen (PCNA) in supraglottic carcinoma.

It is widely accepted that tumor invasion and metastasis are the primary causes for the lethal clinical outcome of cancers. In recent years, attention has been drawn to PCNA (Proliferating Cell Nuclear Antigen) to predict the prognosis of some cancers. In the present paper, we have studied anti-PCNA antibody PC10 in supraglottic cancer by means of immunohistochemistry using paraffin-embedded sections, to demonstrate its clinical significance in this type of malignancy. Twenty-two patients with supraglottic cancer, including T1 (5 cases), T2 (13 cases) and T4 (4 cases) with N- (14 cases) and N+ (8 cases), were investigated for the PCNA expression. The percentages of PCNA positive cells were divided into three groups: < 25%, 25-75%, > 75%, with the range from 10.6 to 95.2%. Results showed that PCNA was well correlated with lymph node metastasis, and appeared to have an inverse correlation with histopathological grades. In this small group, we did not find that PCNA was correlated with T stages and tumor size. However, compared with other T-stages and tumor sizes, the correlation between lymph node metastasis and PCNA seemed to have more clinical significance in T2-stage and in tumors larger than 2 cm. PCNA could be used as a marker in predicting the clinical outcome in supraglottic cancers. An analysis on a large scale is anticipated.

Adult↗

Mycotic sinusitis.

In recent years, Extramucosal Fungal Sinusitis (EFS) in immunocompetent hosts have aroused increasing interest from both clinicians and pathologists. Histopathologically, they are characterized by the presence of fungal hyphae in the lumen of the sinus with no tissue invasion. They include two different entities: the mycetoma and the atopical fungal sinusitis (AFS). The mycetoma is the most frequent and best recognized form of EFS. The clinical picture is that of a unilateral symptomatic chronic sinusitis, often painful, unresponsive to appropriate medical treatment. CT scanning is very evocative in most cases. Definitive diagnosis requires histological and bacteriological examinations of the sinus contents. Surgery is the treatment of choice. Additional antifungal therapy is not indicated unless there is fungal tissue invasion. AFS is a distinct form of EFS. It typically occurs in an atopic patient with a long story of either chronic sinusitis or recalcitrant nasal polyposis recurring after adequate medical treatment or previous sinus surgery. Histopathologically, the pathognomonic pattern shows an "allergic mucin" and scanty fragmented fungal hyphae. Culture is the only way to identify the causative agent. Management should include wide radical sinus surgery combined with long-term nasal steroids. In spite of proper medico-surgical management, the prognosis remains variable and recurrences frequently arise.

Administration, Intranasal↗

Reperfused ischemia of the rat intestine: detection by MR imaging with polylysine-Gd-DTPA enhancement.

To detect reperfused ischemia of the rat intestine, T2-weighted spin-echo images were acquired, followed by T1-weighted images before and after administration of polylysine-Gd-DTPA or Gd-DTPA. Before administration of the contrast agent, the reperfused intestine was hyperintense on T2-weighted images, and to a lesser extent on T1-weighted images. After administration of polylysine-Gd-DTPA, the reperfused intestine enhanced more than the normal one, giving a significantly better contrast-to-noise (CNR) ratio than on unenhanced images. Gd-DTPA induced the same enhancement of the reperfused and the normal intestine and the CNR was lower than on unenhanced T2-weighted images. Reperfused intestinal ischemia could thus be better detected on polylysine-Gd-DTPA-enhanced MR images than on unenhanced images or on Gd-DTPA-enhanced images.

Animals↗

Unusual presentation of papillary thyroid carcinoma: about two cases.

The papillary carcinoma is the most common cancer of thyroid but its presentation may be unexpected. In the first case, a 18-year-old girl complained of a painful enlargement of the right thyroid lobe. Upon the basis of a CT scan revealing punctuate calcifications suggesting psammoma bodies and a right-sided cold nodule on thyroid radioiodine scanning, the patient had a thyroidectomy. The second case was a discovery of papillary carcinoma in a 49-year-old woman who had a thyroidectomy for Graves' disease. This association may not be fortuitous. The cancer could be more aggressive in this group of patients, as TSI play a pathogenic role.

Adolescent↗

Choanal polyp of sphenoidal origin. Report of two cases.

Clinical presentation and Imaging of two cases of choanal polyp extruding from the sphenoid sinus are presented. The clinical, radiological and pathological features of the choanal polyp are reviewed. The major role of radical endoscopic sinus surgery consisting of a complete removal of the polyp and of its insertion into the paranasal sinus cavity is emphasized.

Adolescent↗