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Biomedical subjects

M Antoine

Publications and source records attributed to M Antoine.

At least 19 recordsLinked to original sources
PubMed1998

Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome.

Tumor infiltrate, predominantly constituted by lymphocytes, may represent an important prognostic factor in bronchioloalveolar carcinoma (BAC), in addition to tumor extension and histological type. In the present study, we determined the presence, the origin, and the prognostic importance of neutrophils that also participate in leukocyte infiltrates of BAC. Neutrophil alveolitis was determined immunohistochemically in both lung biopsies and bronchoalveolar lavage (BAL) fluid samples from 29 patients with histologically proved BAC. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoenzymatic techniques. Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's univariate and stepwise multivariate models. Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tract of patients with BAC. Neutrophils were located mainly in the alveolar lumen and seldom in alveolar wall whereas lymphocytes were exclusively present in alveolar wall. A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting the involvement of that chemokine in neutrophil recruitment. The tumor cells were the predominant cells that appeared to express IL-8 by immunolocalization. The presence of increased numbers of neutrophils was significantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of death was increased substantially (rate ratio, 5.2; 95% confidence interval, 1.1 to 24.7) among patients with BAL neutrophil percentage of > or = 39% (median of the distribution) as compared with the others. In BAC, neutrophils accumulate in the alveolar lumen. Elaboration of IL-8 by tumor cells may be responsible for this event, which is associated with a significantly higher risk of death.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1997

Fibroblast growth factor 3, a protein with dual subcellular localization, is targeted to the nucleus and nucleolus by the concerted action of two nuclear localization signals and a nucleolar retention signal.

The major isoform of fibroblast growth factor 3 (FGF3) is initiated from a CUG codon, and the resultant product is distributed to the nucleus/nucleolus and secretory pathway. This dual subcellular localization is achieved in part by the competing effects of two classical intracellular targeting signals located near the amino terminus. At the extreme amino terminus is a short stretch of 29 amino acids before a signal peptide necessary for translocation into the endoplasmic reticulum, which is next to an adjacent bipartite nuclear localization signal. The carboxyl-terminal region of FGF3 is also implicated in nuclear/nucleolar localization. We describe here the characterization of carboxyl-terminal signals by showing they are capable of directing a heterologous protein, beta-galactosidase, to the nucleus. Furthermore, appending both the amino- and carboxyl-terminal domains onto beta-galactosidase, reproduces the dual subcellular localization properties of FGF3. Nuclear uptake of FGF3 appears to be signal-mediated since it binds to karyopherin alpha, the nuclear localization signal binding subunit of a heterodimeric receptor of the nuclear import machinery. The import of FGF3 into the nucleus is energy-dependent, and the inhibition of this process has demonstrated the importance of the nucleolar retention signal in nucleoplasmic and nucleolar accumulation.

Amino Acid Sequence↗
PubMed1997

Structure and erythroid cell-restricted expression of a chicken cDNA encoding a novel zinc finger protein of the Cys + His class.

We report the cloning, sequence analysis and expression pattern of chGfi, a zinc finger protein (Zfp)-encoding cDNA that was isolated from a cDNA library constructed with RNA from avian erythroblastosis virus (AEV)-transformed primary chicken erythroblasts. The 1387-bp-long chGfi cDNA encodes a full-length 337-amino-acid (aa) protein that contains six zinc fingers (Zf) of the 2Cys + 2His class at its C-terminus. Immunoblotting experiments with extracts from bone marrow cells detected a 38-kDa protein that corresponds to the M(r) of 38,690 calculated for the protein deduced from chGfi. The chGfi protein is most homologous to the rat Gfi-1 showing a sequence similarity of 92% over the Zf region and only two exchanges within the N-terminal 19 aa that constitute the Gfi-1 repressor domain. Expression of chGfi is only detected in transformed primary erythroblasts, in erythroid cells of the primitive and definitive lineage and in bone marrow cells. chGfi activity does not vary significantly during differentiation of transformed primary erythroblasts of the definitive lineage. No chGfi expression is detected in cells of the myeloid and lymphoid lineages or in a total of nine different organs of adult origin. Our results indicate that chGfi expression is restricted to erythroid cells of the primitive and definitive lineage.

Amino Acid Sequence↗
PubMed1997

Lung rejection occurs in lung transplant recipients with blood chimerism.

BACKGROUND: It has been postulated that chimerism after transplantation might promote graft acceptance. In the present study, we prospectively assessed blood chimerism in 10 lung transplant recipients during the first posttransplant year and investigated whether chimerism was associated with an immunologically stable situation of the graft. METHODS: The recipients' peripheral blood mononuclear cells were obtained before transplantation and at various time points during the first postoperative year. Donor cells were detected using nested polymerase chain reaction amplification of a donor-specific HLA-DRB1 allele. Clinical graft acceptance was determined by the number of rejection episodes. RESULTS: The incidence of blood chimerism was high during the first 3 postoperative months and then decreased over time. All patients experienced at least one acute rejection episode, and three patients developed chronic rejection. CONCLUSION: We, thus, conclude that rejection of the lung allograft may occur in the presence of blood chimerism.

Adolescent↗
PubMed1997

Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation.

BACKGROUND: Lung function is altered by infection and rejection in patients who undergo heart-lung transplantation. The sensitivity, specificity, and positive/negative predictive values (PPV and NPV) of lung function for the detection of allograft dysfunction in these patients were measured. METHODS: Thirty three patients who underwent heart-lung transplantation were followed for a mean period of 16.3 months. On 123 occasions functional measurements were obtained at the time a transbronchial biopsy specimen and/or bronchoalveolar lavage fluid was taken, which were used as gold standards. Optimal sensitivity (the value for which sensitivity equals specificity) was computed for each functional test from receiver-operator characteristic (ROC) curves. RESULTS: Acute rejection was present on 31 occasions and infection on 36 occasions; 56 samples were normal. Infection and rejection were accompanied by airflow obstruction, a rise in the slopes of the alveolar plateaus for nitrogen, hexafluoride sulphur and helium (SN2, SSF6, and SHe), and a decrease in the difference between SSF6 and SHe (delta S), total lung capacity (TLC), and lung transfer factor (TLCO). Optimal sensitivities for SHe, mid forced expiratory flow (FEF25-75), TLC, and forced expiratory volume in one second (FEV1) were 68%, 67%, 66%, and 60%, respectively; they were not different for infection and rejection and did not change over the study period. For infection and rejection together, PPV ranged from 72% to 88% and NPV from 27% to 52% according to the functional test and the postoperative period considered. CONCLUSIONS: Indices of ventilation distribution, FEF25-75, and TLC have the best optimal sensitivity for the diagnosis of infection and rejection after heart-lung transplantation. The high PPV of pulmonary function in detecting allograft dysfunction observed in this study suggests that a diagnostic procedure should be performed whenever one or more functional tests deteriorate; conversely, the low NPV indicates that a stable pulmonary function does not rule out allograft dysfunction.

Adolescent↗
PubMed1997

MDR1-Pgp 170 expression in human bronchus.

MDR1 P-glycoprotein (Pgp 170), a member of the adenosine triphosphate (ATP) binding cassette transporters, acts as an efflux pump for various hydrophobic agents, particularly for xenobiotics such as benzo(a)pyrene. It has also been shown to regulate cell-volume activated chloride channels. Pgp 170 could, therefore, be of particular importance in cellular mechanisms of defence in the airways and in the control of mucus layer composition. For these reasons, we evaluated the precise localization of Pgp 170 in human adult airways. Fresh non-neoplastic bronchial specimens were collected from 33 patients (26 smokers, four exsmokers and three nonsmokers) who underwent surgery for lung carcinoma. The presence of MDR1 messenger ribonucleic acid (mRNA) was demonstrated by reverse transcriptase chain reaction (RT-PCR) in bronchial epithelial cells collected by gentle scraping from either smokers, exsmokers or nonsmokers. Immunodetection of Pgp 170 using a panel of monoclonal antibodies (MRK16, JSB1, C219, C494) was performed either on cryostat or paraffin-embedded sections of histologically normal bronchial tissue. Pgp 170 was constantly detected with intense labelling at the apical surface of ciliated epithelial cells from the surface epithelium or ciliated collecting ducts, and on apical and lateral surfaces of serous cells from bronchial glands. No staining of mucus-secreting cells was observed. Pgp 170 was also demonstrated at the luminal surface of endothelial cells of bronchial capillaries. In conclusion, the expression of MDR1 P-glycoprotein in bronchial structures, particularly at the epithelial apical surface, suggests important roles for this transmembrane protein in human airways.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Primary pulmonary lymphoma].

There are three distinct clinico-anatomical entities today covered by the definition of a primary clonal pulmonary lymphoid proliferation. These are pulmonary lymphomas of B cell phenotype, of low grade malignancy, B cell lymphomas of high grade malignancy and finally lymphomatoid granulomatosis whose clonal characteristic is sometimes difficult to confirm. This general review aims to specify the pathophysiological, diagnostic, prognostic and therapeutic aspects of these different types. Low grade B cell lymphoma is the most common pulmonary lymphoma. Their development depends on mucosa associated lymphoid tissue. They are most often indolent and present as a chronic alveolar opacity. Their prognosis is excellent and the modalities of treatment are discussed (no therapy, surgery or monochemotherapy). High grade B cell pulmonary lymphomas are much rarer and may result from the transformation of a low grade lymphoma or arise in a particular situation such as imunodepression. Their prognosis is poor and the therapeutic possibilities depend most often on the underlying disease. The presence of lymphomatoid granulomatosis in this group of pulmonary lymphomas is debatable. The demonstration of a clonal character of this proliferation is practically never obtained and there is often extra pulmonary disease. The prognosis of this type of illness is extremely variable because certain studies have shown a cure using corticosteroids and cyclophosphamide whilst others have found that the disease is always fatal in spite of using strong polychemotherapy.

Humans↗
PubMed1997

Torsion of an intra-abdominal testicle in a neonate. Case report and review of the literature.

The thirty-ninth reported case of torsion of an intra-abdominal testicle is described in a neonate. The gonad was excised as is recommended because of the high incidence of malignancy (60% of 37 cases). Torsion of an intra-abdominal testicle should be considered where an abdominal mass with calcification is found in an infant with undescended testis. Ultrasonography improves the diagnostic accuracy in infants because of the cystic nature of these masses in this age group.

Cryptorchidism↗
PubMed1997

[Multicentric Castleman's disease with mediastinal involvement in a patient with HIV infection].

Castleman's disease is most often seen by a thoracic physician as a mediastinal tumour which is discovered fortuitously and whose surgical excision leads to a cure. We report a case of a patient of 30 who was seropositive for HIV and was suffering from Castleman's disease initially localised to the mediastinum. The disease was associated with a cutaneous and bronchial Kaposi sarcoma. The mediastinal disease, associated with cutaneous and bronchial Kaposi sarcoma, was marked by evolving in a multicentric manner. We review the histological definition and recent data concerning the pathophysiology and the diagnostic and therapeutic management of this disorder and the very varied clinical expression.

Adult↗
PubMed1997

[Pulmonary mucormycosis in a leukemia patient. Diagnostic and therapeutic difficulties].

The observation of pulmonary mucormycosis occurring in a patient presenting with aplasia induced therapeutically during treatment for acute myeloblastic leukaemia, has led to a review of the characteristics of this rare opportunistic fungal infection: it occurs in a particular condition; the clinical manifestations are characterised by the thrombotic character and the rapidly necrosing nature of the histological lesions; the diagnosis is usually very difficult to make and is linked to the rarity of the pathology and the frequently negative mycological specimens apart from tissue biopsies; the value of a medicosurgical therapeutic strategy on which the prognosis of the infection depends.

Amphotericin B↗
PubMed1997

[Stereotactic core biopsy of breast microcalcifications. Aid to diagnosis?].

We assessed the accuracy with which stereotactic core biopsy of breast microcalcifications helps to justify follow-up or indicate required surgical planning. Eighty-nine patients underwent stereotactic breast biopsy performed with large core needles. Histopathologic findings of microbiopsies were correlated with radiological findings, with follow up and with surgical findings. Agreement between radiological and histopathologic findings on biopsies was obtained in 86% for benign results. Even in the case of benign radiological findings, the histological results of microbiopsies required a surgical biopsy justified in 10% of cases. Radiologically suspicious or malignant microcalcifications were correlated with 35% benign and 65% malignant histologies on biopsies. The positive predictive value, negative predictive value and accuracy were respectively 93%, 86% and 95%. Invasive lesions were found on microbiopsies in 39% of excised malignant lesions. Multifocal lesions were proved on microbiopsies in 50% of all excised carcinomas. Microbiopsies help to disclose malignant lesions undetected on radiological analysis, and may obviate diagnostic surgical biopsy in many cases.

Adult↗
PubMed1996

[From pseudolymphomas to primary pulmonary lymphomas of MALT type].

Primary lung lymphomas are uncommon and the use of immunohistochemical and molecular biological techniques have widely contributed to their understanding. Generally, they are of low grade malignancy and most develop from mucosa-associated lumphoid tissue (MALT). Cellular analyses of samples obtained routinely by endoscopy (transbronchial biopsy or bronchoalveolar lavage) will probably enable the clinician to avoid invasive diagnostic procedures, such as surgical lung biopsy. Treatment of limited forms is usually surgical. As to bilateral forms or those with lesions of other mucosae e.g. gut, the best therapeutic strategy remains to be defined.

Diagnosis, Differential↗
PubMed1996

Ca2+/calmodulin kinase types II and IV regulate c-fos transcription in the AtT20 corticotroph cell line.

In the corticotroph cell line AtT20, Ca2+ stimulates c-fos mRNA and nuclear c-fos protein accumulation. We show that Ca2+ stimulates transcription of a chloramphenicol-acetyl-transferase reporter gene driven by the c-fos promoter. This effect is mimicked by both constitutively active Ca2+/calmodulin-dependent protein kinase types II (CamK II) and IV (CamK IV). The effects of CamK IV are synergistic with those obtained by cAMP stimulation, whereas CamK II-dependent transcription is not further stimulated. Deletion of the distal promoter sequence revealed that CamK IV, and to a lesser extent CamK II, activate a cis-acting element(s) located between -99 and -53 bp prior to the transcription initiation site. Moreover, CamK II further stimulates transcription through the fos AP1-like element. CamK IV has a lower effect on this element but represses the serum response element. The latter observation might account for the lower transcriptional effects of CamK IV on the full length c-fos promoter.

Animals↗
PubMed1996

Steroid administration in heart and heart-lung transplantation: is the timing adequate?

BACKGROUND: The release of cytokines after cardiopulmonary bypass may play an important role in postoperative morbidity. The release of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6 and IL-8, is even greater in patients undergoing heart transplantation (HTx) than coronary artery grafting. We tested the hypothesis that in HTx patients the earlier administration of steroids, before rather than after cardiopulmonary bypass as usual, can reduce the inflammatory response. METHODS: In 20 consecutive patients who underwent HTx or heart-lung transplantation (HLTx), plasma levels of tumor necrosis factor alpha, IL-6, IL-8, and anti-inflammatory cytokine IL-10 were measured before heparin administration, at aortic cross-clamping and declamping, and 0.5, 1, 1.5, 2, 4, 12, and 24 hours after aortic declamping. In 10 patients (group I, 6 HTx and 4 HLTx), 500 mg of methylprednisolone was first given as usual at 1.5 hours after aortic declamping (at the end of cardiopulmonary bypass). In the next 10 patients (group II, 6 HTx and 4 HLTx), the first doses of methylprednisolone were given 1 hour before operation. In both groups, 125 mg of methylprednisolone were given every 8 hours thereafter during the first postoperative day. RESULTS: The ischemic time and cardiopulmonary bypass time were similar in the two groups (166 +/- 16 minutes versus 157 +/- 13 minutes, and 192 +/- 21 minutes versus 186 +/- 20 minutes, respectively, mean +/- standard error of the mean). At 30 minutes after aortic declamping and throughout the next 4 hours, tumor necrosis factor alpha levels were significantly lower in group II than in group I (all p < 0.03). Interleukin-8 values 1 hour after declamping were also lower in group II than in group I (49 +/- 15 pg/mL versus 130 +/- 38 pg/mL, p < 0.02). Interleukin-10 levels were significantly higher in group II than in group I from 30 minutes after declamping through 2 hours after (all p < 0.03). Interleukin-6 levels were similar in the two groups. CONCLUSIONS: Earlier steroid administration in the immunosuppressive protocol for HTx or HLTx may be preferable to reduce the inflammatory response to cardiopulmonary bypass, as reflected by a lower production of tumor necrosis factor alpha and IL-8, and a greater release of IL-10.

Adult↗
PubMed1996

[Microangiopathic hemolytic anemia associated with uterine sarcoma: report of a case. Review of the literature].

Microangiopathic hemolytic anemia (MAHA) is a rare but severe complication of neoplastic disease. The diagnosis of thrombotic microangiopathy is based on a triad of a hemolytic anemia with schistocytes, thrombocytopenia, and renal failure. Carcinoma-associated MAHA and chemotherapeutic-induced MAHA have been described. Because of differences concerning prognosis and treatment it is important for the clinician to distinguish these two syndromes. However, to our knowledge, this is the first case of a sarcoma-associated thrombotic microangiopathy.

Anemia, Hemolytic↗
PubMed1996

Human cytokine responses to cardiac transplantation and coronary artery bypass grafting.

Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8. To elucidate the pathophysiology of this cytokine response, we explored the possible differences in cytokine responses between patients undergoing heart transplantation and those undergoing coronary artery bypass grafting. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured in eight patients undergoing heart transplantation (mean age 44 years) and eight patients undergoing coronary artery bypass grafting (mean age 61 years). Duration of cardiopulmonary bypass and ischemic time were both longer in the heart transplantation group than in the coronary artery bypass grafting group (133 +/- 26 min vs 100 +/- 31 min, p < 0.05, and 130 +/- 47 min vs 58 +/- 21 min, p < 0.005, respectively). Samples were collected before heparin administration, at aortic crossclamping and declamping, and at 0.5, 1, 1.5, 2, 4, 12, and 24 hours after declamping. Tumor necrosis factor-alpha levels were significantly higher 30 minutes after aortic declamping in the heart transplantation group than in the coronary artery bypass grafting group (68 +/- 30 vs 18 +/- 5 pg/ml, p < 0.05). Interleukin-6 and interleukin-8 levels were also significantly higher 90 minutes after declamping in patients undergoing heart transplantation than in those undergoing coronary artery bypass grafting (310 +/- 63 vs 169 +/- 24 pg/ml, p < 0.05, and 73 +/- 17 vs 24 +/- 5 pg/ml, p < 0.01, respectively). Furthermore, interleukin-6 and interleukin-8 values 90 minutes after declamping were significantly correlated with the ischemic time (r = 0.72 and r = 0.82, respectively, both p < 0.05). Interleukin-10 levels in both groups rose to reach a peak value of around 115 pg/ml 1 hour after declamping. Patients undergoing heart transplantation exhibited a second peak of tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels 12 hours after declamping, probably related to the administration of rabbit antihuman thymocyte immunoglobulin (Thymoglobuline) 3 hours after declamping. Interleukin-6 levels decreased more significantly 12 and 24 hours after declamping in patients undergoing heart transplantation, probably related to methylprednisolone therapy. In conclusion, cardiopulmonary bypass is associated with the production of both proinflammatory and antiinflammatory cytokines. The production of proinflammatory cytokines in patients undergoing heart transplantation is higher than that in patients undergoing coronary artery bypass grafting, and this increase could be related to the longer duration of ischemia in the former group. The later course of cytokine levels after heart transplantation may be further influenced by immunosuppressive therapy.

Adolescent↗