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Biomedical subjects

M C Copin

Publications and source records attributed to M C Copin.

At least 73 records · Page 4Linked to original sources

Immunoreactivity for interleukin 3 and 5 and granulocyte/macrophage colony-stimulating factor of intestinal mucosa in bronchial asthma.

T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.

Adolescent↗

Characterization, quantification, and localization of passenger T lymphocytes and NK cells in human liver before transplantation.

Quantification and localization of the main lymphocyte populations were studied in the livers of normal (n = 8) and brain dead (n = 8) subjects. Cytometric analysis performed on mononuclear cell suspensions obtained from liver biopsies was compared to an automatic image analysis of immunostained sections. The overall number of liver associated lymphocytes was in the usual range of peripheral blood content (2 to 9x10(9) cells). Phenotypic analysis showed predominant NK and CD8+ cells that highly expressed class II antigen and CD25 and CD69 activation markers. Quantitative mapping of these activated lymphocytes revealed their preferential localization in the portal tract and the perisinusoidal area as compared to the pericentrolobular zone, especially in donor livers. This strategic localization could suggest a possible early cooperation between donor lymphocytes and initial infiltrating cells from the recipient and could explain the special immunological status of allografted livers.

Biopsy↗

Experimental models of tracheobronchial stenoses: a useful tool for evaluating airway stents.

BACKGROUND: Stent implantation is a conservative alternative to open operation for treating benign tracheobronchial strictures. Most of the presently available stents were primarily designed for endovascular use. Their respiratory use entails a risk of iatrogenic complications. From a scientific and from an ethical point of view these risks justify preclinical evaluation of new respiratory stents in experimental models of central airway stenoses. Therefore, an attempt was made to develop such models in piglets and adult minipigs. METHODS: Tracheal stenoses were obtained by creating first a segmental tracheomalacia through extramucosal resection of cartilaginous arches. The fibrous component of the stenoses was then obtained through bronchoscopic application of a caustic agent causing progressive deep mucosal and submucosal injury. Stenoses of the main bronchi were created by topical application of the caustic agent only. RESULTS: These models demonstrated the typical features of benign fibromalacic tracheobronchial stenoses with constant recurrence after mechanical dilation. Preliminary experiments showed that short-term problems of tolerance of stent prototypes are easily demonstrable in these models. CONCLUSIONS: These experimental models, which simulate quite realistically human diseases, offer the opportunity to perfect new tracheobronchial stents specifically designed for respiratory use and to evaluate their long-term tolerance before their use in humans.

Animals↗

Bronchioloalveolar carcinoma and congenital cystic adenomatoid malformation.

We report on a 42-year-old woman in whom was discovered a symptomless peripheral radiologic excavated lesion of the lung, which actually existed 3 years before. All investigations were negative. A segmentectomy was performed. Histopathologic examination proved a bronchioloalveolar carcinoma in contact with a type I congenital cystic malformation of the lung. Such a malformation can be diagnosed late in adult life. The epithelial cells of the malformation might predispose to slow proliferation and malignancy, enhanced by smoking habits.

Adenocarcinoma, Bronchiolo-Alveolar↗

Diagnostic and predictive value of an immunohistochemical profile in asymptomatic acute rejection of renal allografts.

We have retrospectively studied the diagnostic and predictive value of immunohistochemical characterization of adhesion molecules (ICAM-1, CD54, VCAM-1) and HLA-DR antigen in a homogeneous clinical group of 36 patients. Between 1 January 1991 and 31 January 1993, 130 patients received a kidney transplant in our unit. Biopsies of renal allografts were only performed in asymptomatic patients who had graft dysfunction, revealed by an isolated serum creatinine increase. Available frozen samples were included in this study (n = 44). The 35 cases of acute rejection diagnosed by biopsy corresponded to mild acute rejection according to the Banff classification criteria. First, we compared the expression of HLA-DR, ICAM-1 and VCAM-1 to morphological data to determine if the immunohistochemical data improved the histopathological diagnosis when the interstitial infiltrate was mild with slight tubulitis. We also studied the phenotype of infiltrating cells with monoclonal antibodies directed against T helper cells, T cytotoxic-suppressor cells, activated T cells and macrophages. Expression on tubular epithelium and density of each type of cell was graded semiquantitatively. Expression of HLA-DR, ICAM-1 and VCAM-1 was observed on tubular epithelium and endothelium in both acute rejection and other causes of graft dysfunction, limiting its diagnostic value. Activated T cells expressing CD69-AIM (activation inducer molecule) and/or HLA-DR were frequently observed in acute rejection (24/35 (69%) and 25/35 (71%) respectively) but not in other causes of renal dysfunction. We then studied the prognostic usefulness of the immunohistochemical profile in acute rejection. Of 27 patients, 12 had a progressively decreased renal function or returned to dialysis within one year after transplantation while the other 15 had a stable graft function after at least 18 months of follow-up. In the group of bad prognosis (n = 12), corticosteroid-resistant rejection episodes were significantly more frequent (p < 0.01). In this group, nine patients had an overexpression of HLA-DR on tubular epithelium versus one patient in the group of stable graft function (chi 2c = 10.57, p < 0.002). Seven patients included in the group of bad prognosis showed tubular overexpression of both ICAM-1 and VCAM-1 versus one patient in the other group chi 2c = 6.23, p < 0.02). Moreover, patients of the first group had a significantly higher number of interstitial macrophages as compared with those who had stable graft function (chi 2c = 4.87, p < 0.01). Thus, our data show that the immunohistochemical profile studied is of little value in the diagnosis of renal allograft rejection. However, an intense tubular expression of HLA-DR and/or both ICAM-1 and VCAM-1, and a high number of interstitial macrophages are significantly related to unfavorable graft outcome.

Acute Disease↗

Bronchogenic cysts of the mediastinum.

During a 25-year period 69 patients whose ages ranged from 1 day to 64 years were treated for bronchogenic cyst of the mediastinum. The male-to-female sex ratio was 1:0.76. The cysts were symptomatic in 63.7%, compressive in 43.4%, and life threatening in 2.8% of cases. Symptoms and signs of compression were more frequent in infants and children than in adults. Such symptoms and signs were more dependent on the location of the cyst than on its volume. The preoperative diagnosis was wrong in 16% of cases. The cysts were approached through thoracotomy in 67 cases, including one conversion from thoracoscopy, and through cervicotomy and mediastinoscopy in one case each. The cysts opened into the respiratory tract in five cases. No communication with the esophageal lumen was observed. The cystic contents were apparently infected in three cases, but samples remained sterile at culture. There was one hospital death caused by a centrally located compressive cyst that was undiagnosed at thoracotomy. The postoperative morbidity rate was 13.4%. There were no further symptoms after operation in children, but five adults reported continuing pain or dyspnea. Resection of bronchogenic cysts is recommended because of uncertainties in diagnosis and in evolution.

Adolescent↗

Hilar lymph nodes: identification with spiral CT and histologic correlation.

PURPOSE: To determine the appearance of normal hilar lymph nodes and associated soft tissue at spiral computed tomography (CT). MATERIALS AND METHODS: At spiral CT in 50 healthy patients, peribronchovascular hypoattenuated areas of 42 right and 45 left hila were systematically evaluated. Histologic results were correlated in five additional cases. RESULTS: Hilar lymph nodes were depicted (a) in the right hilum (lateral to A2 [n = 33 (79%)], medial [n = 29 (69%)] or lateral [n = 11 (26%)] to the interlobar pulmonary artery, and medial to the lower-lobe pulmonary artery [n = 30 (71%)], A7 [n = 9 (21%)], and A8-10 [n = 8 (19%)]; and (b) in the left hilum (lateral to A2 [n = 22 (49%)], medial to the interlobar pulmonary artery [n = 45 (100%)], and the lower-lobe pulmonary artery [n = 27 (60%)], and in the angles of bifurcation of A7 + 8 and A9 + 10 [n = 18 (40%)]). Hilar lymph nodes were seen to be triangular or linear and to be less than 3 mm wide except around the left-lower-lobe pulmonary artery. CONCLUSION: Spiral CT accurately depicts normal hilar lymph nodes and their major anatomic relationships.

Contrast Media↗

Expression of E-selectin, ICAM-1 and VCAM-1 on bronchial biopsies from allergic and non-allergic asthmatic patients.

The bronchial mucosa of asthmatic patients is characterized by a large influx of eosinophils, monocytes and lymphocytes. Leucocyte migration and accumulation is thought to involve adhesion molecules, as shown in an animal of allergic asthma and in humans with other allergic diseases. The aim of this study was to evaluate the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) on endothelium and epithelium in bronchial biopsies obtained from patients with allergic (n = 17) and non-allergic asthma (n = 18). Bronchial biopsies were taken in asthmatic patients and control subjects (n = 10) by fiberoptic bronchoscopy and embedded in paraffin. The cellular infiltrate was evaluated by May-Grünwald-Giemsa staining. Adhesion molecule expression was analyzed by immunohistochemistry using mouse monoclonal antibodies; the results were expressed as the percentage of positive cells. For each patient, we evaluated the severity of asthma as defined by the AAS score and the treatment. In controls, low expression of ICAM-1 was observed on the epithelium and endothelium (9.6 +/- 2.7 and 11.2 +/- 4.1%, respectively), while E-selectin and VCAM-1 were not expressed. In patients with allergic asthma, a significant increase of ICAM-1 expression was observed on epithelium and endothelium (28 +/- 5.3 and 35.6 +/- 5%, respectively), whereas E-selectin (17.4 +/- 4.8%) and VCAM-1 (12.8 +/- 3.6%) were overexpressed only on endothelium. In allergic asthmatic patients, adhesion molecule expression on endothelium was correlated with eosinophil and total leucocyte infiltrate (p < 0.05). In contrast, adhesion molecule expression in biopsies from patients with non-allergic asthma (14.1 +/- 5.2 and 15.3 +/- 3.6% for ICAM-1 expression on epithelium and endothelium, respectively) was not significantly different from the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Diagnostic tests for pneumonia in ventilated patients: prospective evaluation of diagnostic accuracy using histology as a diagnostic gold standard.

The diagnostic accuracy of protected-specimen brush (PSB), bronchoalveolar lavage (BAL), and endotracheal aspirates (EA) was prospectively evaluated in a series of 28 mechanically ventilated patients (MV patients) who died within 3 d of the bronchoscopic procedure, using postmortem lung examination as the gold standard for establishing the diagnosis of pneumonia. The entire fixed lungs were carefully dissected along the bronchovascular axes and each segment was cut into 5- to 10-mm thick sections, enabling gross examination of the lung parenchyma. Two tissue blocks were taken from each segment, including grossly abnormal areas whenever present. In several cases, two peripheral (subpleural) lung-tissue blocks were also taken from each lobe prior to systematic dissection of the lungs. Quantitative cultures (QC) and direct cytologic and microbiologic examination (DE) was performed on respiratory samples obtained within 72 h before death. Values of 10(3) cfu/ml of Ringer's solution, 10(4) cfu/ml of retrieved fluid, and 10(6) cfu/ml of respiratory secretions were used as cutoff points for quantitative PSB, BAL, and EA cultures, respectively. The main findings in this study were that: (1) Pneumonia was present in 67% of the patients. (2) Histologic lesions of pneumonia were mainly bilateral and predominated in the dependent lung segments. (3) Coexistence of a variety of noninfectious processes was a common finding in patients with pneumonia. (4) In several cases pneumonia was absent from peripheral lung samples while more central areas of the same segment displayed typical foci of pneumonia. (5) The sensitivity of quantitative cultures was 55%, 57%, and 47% for EA, PSB, and BAL, respectively, and the specificity was 85%, 88%, and 100%, respectively. Reducing the diagnostic threshold of EA to 10(5) cfu/ml of respiratory secretions instead of 10(6) cfu/ml resulted in a sensitivity of 63.1% and a specificity of 75% for EA. The sensitivity of direct examination (DE) was 50%, 47%, and 47%, respectively, and the specificity was 75%, 88%, and 87%. (6) The presence of intracellular organisms (ICO) in BAL had a 36.8% sensitivity and 100% specificity in establishing the diagnosis of pneumonia regardless of their percentage. (7) Although 15 patients (53%) were not on antibiotics or were off antibiotics for more than 48 h before testing, no relationship could be established between the patients' antibiotic status and the result of any diagnostic test. By using a recommended methodology for respiratory sampling techniques together with complete postmortem lung examination as a diagnostic "gold standard," this study provides a realistic insight into the diagnostic values of EA, PSB, and BAL in MV patients with suspected pneumonia.

Biopsy↗

[Erdheim-Chester disease. Clinico-pathologic study of two cases].

Erdheim-Chester disease is a rare visceral xanthogranulomatosis characterized by bilateral, symmetrical sclerosis of the metaphyseal regions of long bones and infiltration of foamy, lipid-laden histiocytes. Clinically, it ranges from an asymptomatic, focal process to a fatal, systemic disease. We report two new cases, different in their presentation and extension.

Female↗

[Acinar cell carcinoma of the pancreas revealed by Weber-Christian syndrome].

Acinar cell carcinoma of the pancreas is a rare tumor of the exocrine pancreas that may be associated with a characteristic syndrome of disseminated fat necrosis with a bad prognosis. We report a case of this tumor occurring in a 63 year-old man who presented with polyarthralgia and panniculitis of the legs. The histological features and the differential diagnosis of acinar cell carcinoma are discussed.

Carcinoma, Acinar Cell↗

Induction of calbindin-D 28K gene and protein expression by physiological stimuli but not in calcium-mediated degeneration in rat PC12 pheochromocytoma cells.

To understand the role of calbindin-D 28K in neuronal degeneration, we examined its expression in differentiated PC12 cells in response to calcium intoxication, using the ionophore A23187 treatment, that results in cell degeneration and death. We first established that calbindin-D 28K is expressed in PC12 cells. The amounts of calbindin-D 28K mRNA and protein were increased by the differentiation factors, NGF and retinoic acid, but not by vitamin D3. Calbindin-D 28K expression was also significantly up-regulated by stimuli (depolarization, low concentrations of Ca2+ ionophore A23187) which increase intracellular calcium levels within the physiological range. In contrast, the calbindin-D 28K mRNA and protein concentrations were not modulated by high concentrations of A23187, which resulted in cell degeneration and death. Experiments with the antisense oligonucleotides showed that, although the calbindin-D 28K protein levels were decreased significantly, the progression of degenerative changes induced by calcium via A23187, was not altered.

Animals↗

Protective effect of rSm28GST-specific T cells in schistosomiasis: role of gamma interferon.

Immunization with a single dose of 50 micrograms of recombinant Schistosoma mansoni 28-kDa glutathione-S-transferase (rSm28GST) was able to induce a reduction in the worm burden, the number of eggs, and the degree of hepatic fibrosis as quantified by the measurement of collagen content in the liver of S. mansoni-infected mice. No relationship was found between anti-Sm28GST immunoglobulin G and immunoglobulin A titers and the levels of protection obtained. Adoptive transfers of Sm28GST-specific total, CD4+, or CD8+ T cells reproduced the protective effect obtained with the recombinant molecule. Moreover, experiments studying in vivo T-cell depletion demonstrated that anti-CD4- or anti-CD8-treated mice showed a significant decrease in the protective effect conferred, suggesting a role of the two T-cell subpopulations in the expression of Sm28GST-mediated protection against hepatic damage. Sm28GST-specific cells produced little interleukin-4 and high levels of gamma interferon. Treatment of immunized mice with anti-gamma interferon antibody totally suppressed the Sm28GST-induced protective effect and led to the rapid death of infected animals, suggesting a role for this cytokine in the expression of the protective immunity obtained after immunization with rSm28GST.

Animals↗

Evidence for eosinophil activation in eosinophilic cystitis.

Eosinophilic cystitis (EC) is a rare condition. Recent studies have shown that activated eosinophils release cytotoxic cationic proteins which can induce tissue damage. Moreover, in vitro studies have shown that interleukin-5 (IL-5) is a cytokine able to attract and activate eosinophils. The goal of this study was to detect a possible activation of eosinophils in EC using electron microscopy, in situ hybridization with an IL-5 RNA probe and immunochemistry with a specific anti-IL-5 antibody. Using these combined methods in a typical case of EC, we found numerous activated eosinophils synthesizing and secreting IL-5 protein. IL-5 could enhance the activation of eosinophils and their cytotoxic potential in bladder tissues. This mechanism might explain the chronicity of the lesions in EC.

Cystitis↗

Airway-like inflammation of minor salivary gland in bronchial asthma.

T-lymphocytes are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate the histologic abnormalities of a minor salivary gland (MSG) associated with bronchial asthma. Fifty-eight asthmatic patients were prospectively studied (37 women, 21 men; mean age, 54 +/- 6 yr). Twenty-nine patients had allergic asthma (AA) and 29 had nonallergic asthma (NAA). Results were compared with those obtained from 15 healthy control subjects and 15 nonasthmatic patients with chronic obstructive pulmonary disease (COPD). MSG was normal in 14 of 15 patients with COPD and in 14 of 15 control subjects. Forty-three of 58 (74%) asthmatic patients presented MSG abnormalities. These were significantly more frequent in asthmatics (74%) than in patients with COPD and healthy control subjects (6%, p < 0.001 versus asthmatics) and in NAA (97%) than in AA (52%, p < 0.01). The main pathologic features of MSG in asthma were T-lymphocyte infiltration (57%: AA nine of 29; NAA 24 of 29), partly degranulated mast cells (64%: AA, 11 of 29; NAA, 26 of 29), basement membrane thickening (64%: AA, 11 of 29; NAA, 26 of 29), and endothelial cell changes (26%: AA, one of 29; NAA, 14 of 29). Eosinophils were found only in two cases. Expression of ICAM-1 was demonstrated in nine of 16 patients with NAA, whereas VCAM-1 and E-selectin were negative in all of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗