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Biomedical subjects

M C Copin

Publications and source records attributed to M C Copin.

At least 37 records · Page 2Linked to original sources

Solitary fibrous tumour of the kidney.

Solitary fibrous tumours are relatively rare neoplasms initially described in the pleura. Such lesions are now reported in many extrathoracic sites. To our knowledge, only 8 cases have been reported in the kidney. All these cases were benign. We report a patient with a solitary fibrous tumour of the kidney with infiltration of the wall of the renal vein. Microscopic examination showed proliferation of spindle cells with a prominent vascular haemangiopericytoma-like pattern. Hypercellular areas were admixed with hyalinized collagenous zones. The neoplastic cells stained for vimentin and CD34. CD31 was negative. Biologically, we did not find any arguments for malignancy: the flow cytometric study showed diploid histograms, and immunostaining for p53 was negative.

Aged↗

Obstructive fibrinous tracheal pseudomembrane. A potentially fatal complication of tracheal intubation.

A series of 10 consecutive cases presenting an obstructive fibrinous tracheal pseudomembrane (OFTP) as a complication of endo-tracheal intubation is presented. The patients developed a thick tubular, rubber-like, whitish pseudomembrane moulding the tracheal wall as a result of short-duration endotracheal intubation. This pseudomembrane firmly adhered to the tracheal wall at the site of the endotracheal cuff. Shortly after extubation, partial detachment of the proximal part of the pseudomembrane produced intermittent positional acute respiratory failure due to valve-manner tracheal obstruction. Immediate mechanical ablation was curative in nine patients, without secondary development of tracheal stenosis. One patient died from acute asphyxiation. The history and the pathological findings of these cases support the hypothesis that this lesion represents an early stage of ischemic tracheal wall injury related to the cuff pressure. Pulmonary physicians should be alerted on this poorly known complication of endotracheal intubation.

Adolescent↗

Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. I. Stomach. A relationship to gastric carcinoma.

Studies were undertaken to provide information regarding cell-specific expression of mucin genes in stomach and their relation to developmental and neoplastic patterns of epithelial cytodifferentiation. In situ hybridization was used to study mRNA expression of eight mucin genes (MUC1-4, MUC5AC, MUC5B, MUC6, MUC7) in stomach of 13 human embryos and fetuses (8-27 weeks' gestation), comparing these with normal, metaplastic, and neoplastic adult tissues. These investigations have demonstrated that MUC1, MUC4, MUC5AC, MUC5B, and MUC6 are already expressed in the embryonic stomach at 8 weeks of gestation. MUC3 mRNA expression can be observed from 10.5 weeks of gestation. MUC2 is expressed at later stages, concomitant with mucous gland cytodifferentiation. Normal adult stomach is characterized by strong expression of MUC1, MUC5AC, and MUC6, less prominent MUC2, and sporadic MUC3 and MUC4, without MUC5B and MUC7. Intestinal metaplasia is characterized by an intestinal-type pattern with MUC2 and MUC3 mRNA expression. Gastric carcinomas exhibit altered mucin gene expression patterns with disappearance of MUC5AC and MUC6 mRNAs in some tumor glands, abnormal expression of MUC2, and reappearance of MUC5B mRNAs. In conclusion, we have observed that patterns of mucin gene expression in embryonic and fetal stomach could show similarities with some gastric carcinomas in adults. Differences in mucin gene expression in developmental, metaplastic, and neoplastic stomach compared to normal adult stomach suggest a possible regulatory role for their products in gastric epithelial cell proliferation and differentiation.

Adenocarcinoma↗

Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas.

Studies were undertaken to provide information regarding cell-specific expression of mucin genes and their relation to developmental and neoplastic patterns of epithelial cytodifferentiation. In situ hybridization was used to study mRNA expression of mucin genes in duodenum and accessory digestive glands (liver, gallbladder, pancreas) of 13 human embryos and fetuses (6. 5-27 weeks' gestation), comparing these with normal and neoplastic adult tissues. These investigations demonstrated that the pattern of mucin gene expression in fetal duodenum reiterated the patterns we observed during gastric and intestinal ontogenesis, with MUC2 and MUC3 expression in the surface epithelium and MUC6 expression associated with the development of Brünner's glands. In embryonic liver, MUC3 was already expressed at 6.5 weeks of gestation in hepatoblasts. As in adults, MUC1, MUC2, MUC3, MUC5AC, MUC5B, and MUC6 were expressed in fetal gallbladder, whereas MUC4 was not. In contrast, MUC4 was strongly expressed in gallbladder adenocarcinomas. MUC5B and MUC6 were expressed in fetal pancreas, from 12 weeks and 26 weeks of gestation, respectively. Surprisingly, MUC3 which is strongly expressed in adult pancreas, was not detected in developmental pancreas. Taken together, these data show complex spatio-temporal regulation of the mucin genes and suggest a possible regulatory role for mucin gene products in gastroduodenal epithelial cell differentiation.

Adenocarcinoma↗

Inflammatory pseudotumor of the renal pelvis. A report of 2 cases with clinicopathologic and immunohistochemical study.

We describe 2 cases of inflammatory pseudotumor of the renal pelvis. Case 1, the male patient, was 37 years old, and case 2, the female patient, was 54 years old. Both patients presented with macroscopic hematuria and flank pain. Computed tomographic (CT) scan and ureterocystoscopy revealed in case 1 a mass in the left renal pelvis and the calyces. In case 2, urography showed a lacuna of the renal pelvis, and CT scan showed an irregular thickening of the renal pelvis. In both cases, the preoperative clinical diagnosis was urothelial carcinoma, and both patients underwent nephrectomy. Microscopic examination revealed in case 1 a tumor of the renal pelvis composed of spindle cells with eosinophilic cytoplasm in a myxoid and vascular stroma with abundant inflammatory infiltrate. In case 2, the tumor was composed of densely basophilic spindle cells in a fascicular pattern intermingled with lymphocytes and plasma cells and involving the lamina propria of the renal pelvis. The spindle cells reacted strongly with antibody to vimentin and focally with antibodies to smooth muscle actin and muscle-specific actin. In the urogenital tract inflammatory pseudotumor involves preferentially the urinary bladder. Rare cases have been reported in the kidney. The 2 cases presented here are unusual due to the location in the renal pelvis, mimicking urothelial carcinoma.

Adult↗

Overexpression level of stromelysin 3 is related to the lymph node involvement in non-small cell lung cancer.

Proteases contribute to tumor invasion and metastasis via their potential to degrade basement membranes and extracellular matrix. Our aim was to compare the level of several proteases: urokinase-type plasminogen activator (u-PA), matrix metalloproteinase 2 (MMP-2; 72-kDa type IV collagenase, also known as gelatinase A), MMP-11 [also known as stromelysin 3 (STR3)], and cathepsins B and L in resected non-small cell lung cancer. Between June 1996 and March 1998, samples of lung tumor tissues were taken from 119 surgically treated patients. Thirty out of the 119 tumor samples were matched with corresponding adjacent normal tissue. u-PA was measured by a commercially available immunoluminometric assay. Metalloproteinases and cathepsins have been evaluated at the RNA level by Northern blot and quantified with a PhosphorImager. Expression of these proteases was compared to the following clinicopathological parameters: pathological diagnosis, tumor size, exposure to asbestos, radiotherapy, neo-adjuvant chemotherapy, tumor-node-metastasis stage, lymph node involvement, presence of metastasis. u-PA, MMP-2, MMP-11/STR3, and cathepsin B were significantly increased in tumor (the tumor:normal ratio was on average increased by 5.4-, 2.2-, 83.5-, and 2.2-fold, respectively). The tumor:normal ratio of MMP-11/ STR3 was found to be significantly linked to the lymph node involvement (P < 0.05). Our results suggest that several proteases are involved in the invasive potential of non-small cell lung cancer and that the quantification of MMP-11/ STR3 could represent an useful prognostic marker.

Adult↗

Implication of HTLV-I infection, strongyloidiasis, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphomas in an endemic area (Martinique, French West Indies).

A clinicopathologic study was conducted to assess the implication of HTLV-I infection, Strongyloides stercoralis (Ss) infection, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphoma (NHL) in Martinique, French West Indies. Two groups of patients, with 22 and 41 participants with B-cell and T-cell lymphoma, respectively, were analyzed. HTLV-I antibodies were detected in 24 (59%) patients with T-cell lymphoma of whom 19 (46%) fulfilled diagnostic criteria of adult T-cell leukemia/lymphoma (ATLL). By comparison with other T-cell lymphomas, patients with ATLL were significantly younger (52 versus 63 years; p = .03), had a significantly higher incidence of hypercalcemia (60% versus 0%; p = .0001), a trend for higher incidence of digestive tract localization (21% versus 4%; p = .1) and significantly shorter median survival (6 versus 17 months; p = .03). Similar results were observed when all 24 HTLV-I-infected patients with T-cell lymphoma were compared with the 17 seronegative patients. Strongyloidiasis was diagnosed in 11 of 34 patients tested for Ss infection. All 4 Ss-infected (Ss-positive) ATLL patients treated with combination chemotherapy achieved complete remission (CR) versus only 2 of 7 Ss-negative ATLL patients (p = .04). In addition, survival of Ss-positive patients with ATLL was better than that of the uninfected patients: 27 versus 5 months, p = .04, respectively). P53 expression was assessed by immunohistochemistry on lymph node biopsies from 37 patients including 18 B-cell lymphomas, 14 ATLL, and 5 other T-cell lymphomas. P53 overexpression (P53-positive) was observed in 6 samples that corresponded in all 6 patients with ATLL. All P53-positive ATLL patients had stage IV disease with elevated lactate dehydrogenase (LDH) levels. By comparison with other ATLL patients studied for p53 expression, P53-positive ATLL were characterized by a lower response rate to combination chemotherapy (CR: 0 of 6 versus 4 of 6; p = .04) and a shorter survival (2 versus 9 months, p = .04). Our results suggest that ATLL represents almost 50% of T-cell lymphomas in Martinique; Ss infection during ATLL seems to be linked with a high response rate to chemotherapy and prolonged survival; and P53 overexpression is observed in almost 50% of aggressive ATLL from Martinique and, even in advanced clinical subtypes, is associated with resistance to chemotherapy and short-term survival.

Adolescent↗

Developmental mucin gene expression in the human respiratory tract.

The epithelial surface of the respiratory tract is coated with a protective film of mucus secreted by epithelial goblet and submucosal gland cells. Histology of the airway mucosa and composition of secretions during the second trimester of fetal life are known to differ from the normal adult in that these secretions show similarities with those of hypersecretory disorders. To provide information regarding cell-specific expression of mucin genes and their relation to developmental patterns of epithelial cytodifferentiation, we studied the expression of eight different mucin genes (MUC1-MUC4, MUC5AC, MUC5B, MUC6, MUC7) in human embryonic and fetal respiratory tract using in situ hybridization. These investigations demonstrated that MUC4 is the earliest gene expressed in the foregut at 6.5 wk, followed by MUC1 and MUC2 from 9. 5 wk of gestation in trachea, bronchi, epithelial tubules, and terminal sacs before epithelial cytodifferentiation. In contrast, MUC5AC, MUC5B, and MUC7 are expressed at later gestational ages concomitant with epithelial cytodifferentiation. During this developmental stage, MUC1 and MUC4 mRNAs are located in goblet and ciliated cells, whereas MUC2 mRNAs are located in basal and goblet cells. MUC5AC expression is confined to goblet cells. In the submucosal glands, MUC2 mRNAs are located in both mucous and serous cells, whereas MUC5B and MUC7 mRNAs are expressed in mucous and in serous cells, respectively. These data suggest distinct developmental roles for MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 in the elongation, branching, and epithelial cytodifferentiation of the respiratory tract during ontogenesis. Distinct patterns of mucin gene expression are also likely to play an important role in regulating appropriate epithelial cell proliferation and cytodifferentiation in adult airway mucosa as it is indicated by aberrant expression in hypersecretory disorders.

Adult↗

Characterization of an animal model of ventilator-acquired pneumonia.

To develop an experimental model of ventilator-acquired pneumonia (VAP), we investigated whether healthy piglets could develop endogenously acquired pulmonary infection as a result of prolonged mechanical ventilation (MV). Thirty-three piglets underwent MV with anesthesia, analgesia, and paralysis produced by continuous infusion of midazolam, fentanyl, and pancuronium bromide. Ten animals received antibioprophylaxis with ceftriaxone (ATB group) and 23 received no antibiotics (control group). Eighteen control animals and 9 ceftriaxone-treated animals completed the 4-day study protocol. The presence of pneumonia on day 4 was ascertained by multiple pulmonary biopsy specimens, processed for microscopic examination and quantitative cultures. The anesthetic regimen provided satisfactory electrolyte balance and cardiovascular stability. Under these circumstances, 17 of 18 animals and 4 of 9 animals developed VAP in the control and the ATB groups, respectively. Lesions of different grades of severity were unevenly distributed through both lungs with a predominance and a higher severity in dependent lung segments. Noninfectious lesions frequently associated with VAP in humans were not observed. Pneumonia was usually polymicrobial with a predominance of Gram-negative organisms. Most of the causative organisms originated from the oropharynx. Histologic lesions and lung bacterial concentrations were less in the ATB group than in control animals. We then investigated the effects of intrabronchial challenge with bacterial pathogens in the absence of MV. Intrabronchial bacterial inoculation resulted in the development of pneumonia that spontaneously resolved even when using very highly titrated inocula. Therefore, MV seems to be the main predisposing factor in the development of pneumonia in this model. This model that resembles human VAP in its histologic, bacteriologic, and pathogenic aspects may be useful to further study pathogenesis, diagnosis, prevention, and therapy of VAP.

Animals↗

A case of giant chondrosarcoma of the cricoid cartilage presenting as a superior mediastinal tumour.

We report the case of a 73-year-old man operated on for a symptomatic superior mediastinal mass which developed from the cricoid cartilage. Through cervicotomy and partial sternotomy, laryngeal subglottic resection allowed complete removal of the tumour. From pathological examination, a benign chondroma was initially diagnosed without any criterion of malignancy. However, subsequent review of the pathological slides showed the lesion to be a low grade chondrosarcoma with an epithelial quota of spindle cells, responsible for the patient's death. This case illustrates the need for resection of presumed cricoid cartilage chondromas because of their potential mediastinal development and associated malignancies.

Aged↗

Influence of pulmonary bacteriology and histology on the yield of diagnostic procedures in ventilator-acquired pneumonia.

We investigated the influence of pulmonary bacteriology and histology on the yield of diagnostic procedures in a clinically relevant model of ventilator-acquired pneumonia (VAP). Twenty-seven piglets entered a 4-d protocol of ventilatory support under general anesthesia. Endotracheal aspirates (EA), protected specimen brush (PSB), and bronchoalveolar lavage (BAL) were obtained on Day 4. PSB and BAL were performed under bronchoscopic guidance in dependent and nondependent lung segments. Immediately thereafter sternotomy allowed bilateral lung biopsies including the segments studied by bronchoscopic techniques. All respiratory specimens were then processed for microscopic examination and quantitative cultures (QC). In this model where many of the confounding factors often present in human studies were absent, we found that (1) although the local bacterial burden tended to correlate with the presence and the severity of histologic lesions, no definite bacteriologic cutoff could differentiate the histologic presence or absence of pneumonia; (2) histologic lesions of pneumonia and parenchymal bacterial burden were unevenly distributed through the lungs; (3) this heterogeneity in bacterial distribution also held true for single bacterial species; (4) using discriminative values of >= 10(3) cfu/ml, >= 10(4) cfu/ml, and >= 10(5) cfu/ml to define positive PSB, BAL, and EA cultures, respectively, these techniques identified the histologic presence of pneumonia with a sensitivity of 69%, 78%, and 100%, respectively; (5) the specificity of these techniques in recognizing VAP was less than 50%; (6) with these discriminative values, less than 50% of PSB and BAL specimens correctly identified the causative organisms, whereas 94% of EA specimens correctly established the microbiologic diagnosis of pneumonia. We believe that the peculiar histologic and bacteriologic features of VAP may account for the difficulties of PSB and BAL, which combine QC with the use of discriminative thresholds, to reliably recognize pneumonia and to identify the causative organisms. For clinical practice, no technique confidently helps in recognizing pneumonia in mechanically ventilated patients. With regard to bacterial diagnosis, use of quantitative cultures of EA seems to be the best technique to identify the causative organisms in patients suffering VAP.

Animals↗

Transforming growth factor-beta1 in sarcoidosis.

Transforming growth factor-beta (TGF-beta) is a cytokine that promotes extracellular matrix accumulation and inhibits matrix degradation. Although the natural course of sarcoidosis is usually favourable, granuloma healing in the lung may result in pulmonary fibrosis and respiratory impairment in some patients. In this study TGF-beta1 was evaluated in bronchoalveolar lavage (BAL) fluid and culture supernatants of alveolar macrophages (AM) from 73 patients with biopsy-proven sarcoidosis. Disease activity was defined when patients recently developed or increased symptoms (cough, dyspnoea, systemic symptoms) and/or demonstrated increasing opacities on chest radiography. Pulmonary function tests were performed in all patients including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and the diffusing capacity of the lung for carbon monoxide (DL,CO). Fourteen patients with idiopathic pulmonary fibrosis (IPF) and 14 healthy subjects were investigated as a control group. Immunohistochemistry was used to evaluate the cell distribution of TGF-beta1 on lung specimens. TGF-beta1 levels in BAL and in AM supernatants were not different between sarcoidosis and healthy subjects, whereas they were markedly increased in IPF. However, the TGF-beta1 level was significantly increased in BAL fluid but not in AM supernatants from sarcoidosis with altered lung function, compared with patients with normal lung function. The TGF-beta1 level in BAL was increased in active sarcoidosis but this increased level was mainly related to the higher level observed in patients with altered lung function. TGF-beta1 levels in BAL correlated significantly with the lymphocyte percentage. TGF-beta1 staining assessed by immunohistochemistry was intense in epithelioid histiocytes comprising non-necrotizing granuloma and in bronchiolar epithelial cells, in hyperplastic type II pneumocytes and occasionally in AM. This study supports the hypothesis that overproduction of transforming growth factor-beta1 is associated with functional impairment in patients with pulmonary sarcoidosis.

Adult↗

Experimental CVB3-induced chronic myocarditis in two murine strains: evidence of interrelationships between virus replication and myocardial damage in persistent cardiac infection.

In order to analyse the relationships between enteroviral replication and the myocardial damage at the onset of chronic cardiac infection, 2 mouse strains with different degrees of immunological competence (NMRI nu/nu, DBA/2) were infected by a myocarditic Coxsackie virus B3 (CVB3-M1) variant. At 31 days post-inoculation, plaque-forming assay, polymerase chain reaction (RT-PCR), and immunohistochemistry were carried out for detecting viruses and viral components in the myocardium. The virological findings were related to histopathological changes in the myocardium as well to the dilatation of both cardiac ventricles. Chronic myocardial lesions characterized by large fibrosis areas and interstitial inflammatory infiltrates were detected together with cardiomegalia in 52.6% (10/19) of athymic mice and in 9% (2/22) of euthymic mice. Viral replication foci were located and were found only in myocarditic cells adjacent to myocardial inflammatory lesions by immunostaining myocardial tissue sections with anti-serum to VP1 virus capsid protein. Using PCR followed by microwell capture hybridization assay, a large excess of viral positive strand RNA over negative strand was semiquantified in heart tissue from mice with chronic myocarditis, whereas approximately equal amounts of plus and minus strand RNA were detected in cases of persistent cardiac infection without chronic myocardial injuries. These findings provide evidence of the major role of viral replication in the pathogenesis of chronic murine CVB3-induced cardiomyopathy. The results indicate that the cardiac persistence of enteroviral RNAs can be observed without chronic cardiomyopathy, which could be explained by a defective viral positive RNA replication.

Animals↗

POEMS syndrome: report on six patients with unusual clinical signs, elevated levels of cytokines, macrophage involvement and chromosomal aberrations of bone marrow plasma cells.

POEMS syndrome is a multisystemic disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes and various other systemic clinical signs. The pathophysiology of this syndrome remains largely unknown. In order to gain insight into its pathophysiology, we studied the clinical characteristics and performed serum analysis (auto-antibodies, cytokine levels) and phenotypic and cytogenetic studies of bone marrow plasma cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual clinical signs were present in these patients: pulmonary hypertension (two patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a, GD1b and GT1b gangliosides) were found. Sequential evaluations of serum cytokines (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked elevations of IL-6 and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL-6). Using in situ hybridization of these cytokines mRNAs on lymph node specimens of two patients who had an angiofollicular lymph node hyperplasia, a strong positivity was found with the IL-1-beta antisense probe in lymph node macrophages. On skin biopsy a high number of cells expressing TNF-alpha mRNA was observed in the dermis. The biological features of BMPC: phenotype (expression of CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and chromosomal in situ hybridization remained those of BMPC found in monoclonal gammopathy of undetermined significance. We conclude that POEMS syndrome is a hypercytokinemic syndrome in which BMPC are not of malignant type. Macrophages are involved in this syndrome and their role has to be further investigated as well as treatments which act through an anti-cytokine mechanism.

Adult↗

Bronchial arteries in the pig before and after permanent pulmonary artery occlusion.

RATIONALE AND OBJECTIVES: The authors study the bronchial arteries in the adult pig before and after pulmonary artery occlusion. METHODS: The bronchial artery anatomy was analyzed on postmortem aortograms in six pigs in group 1. In 20 animals in group 2, the left diaphragmatic lobar pulmonary artery (DLPA) was proximally (n = 12), medially (n = 5), or distally (n = 3) occluded via angiographic procedures; an unintentional embolization of coils in the right DLPA led to an incomplete pulmonary arterial occlusion. Eight to 12 weeks later, postmortem bronchial angiograms and pathologic studies were performed systematically in group 2. RESULTS: Outcomes in group 1 were: (A) a common trunk to the right and left bronchial arteries found in five animals, and (B) bronchopulmonary anastomoses found in the five lungs optimally injected. Outcomes in group 2 were: (A) the absence of pulmonary infarct and the development of a collateral bronchial supply were constant in the left lung; (B) the left DLPAs were patent beyond the coils and opacified via bronchopulmonary anastomoses; (C) dilated subpleural bronchial arteries were constant in the interlobular septa of the lung parenchyma devoid of pulmonary arterial perfusion; (D) the right bronchial arteries were normal after incomplete pulmonary artery occlusion. CONCLUSIONS: Because of an anastomosed dual circulation, the pig is a reliable experimental model for interventional and surgical procedures.

Animals↗