[Coexistence of breast cystosarcoma phyllodes and bilateral in situ lobular carcinoma].
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Adult↗
Biomedical subjects
F Navarro
Publications and source records attributed to F Navarro.
Roles of chemokines and receptor polarization in NK-target cell interactions.
We report that the ability of NK cells to produce chemokines is increased in NK-target cell conjugates. The chemokines produced play a critical role in the polarization and recruitment of NK cells as well as in the NK effector-target cell conjugate formation. Chemokines induce the formation of two specialized regions in the NK cell: the advancing front or leading edge, where chemokine receptors CCR2 and CCR5 cluster, which might guide the cells toward the chemotactic source, and the uropod, where adhesion molecules ICAM-1 and -3 are redistributed. NK cell polarity was intrinsically involved in conjugate formation. The redistribution of both adhesion receptors and CCR was preserved during the formation of NK-target cell conjugates. Time-lapse videomicroscopy studies of the formation of effector-target conjugates showed that morphologic poles are also functionally distinct; while the binding to target cells was preferentially mediated through the leading edge, the uropod was found at the rear of migrating NK cells and recruited additional NK cells to the vicinity of K562 target cells. Inhibition of cell polarization and adhesion receptor redistribution blocked the formation of NK-K562 cell conjugates and the cytotoxic activity of NK cells. We discuss the implication of NK-cell polarization in the development of cytotoxic responses.
Antigens, CD↗
HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.
We previously showed that the availability of a nonamer peptide derived from certain HLA class I signal sequences is a necessary requirement for the stabilization of endogenous HLA-E expression on the surface of 721.221 cells. This led us to examine the ability of HLA-E to protect HLA class I transfectants from natural killer (NK) cell-mediated lysis. It was possible to implicate the CD94/NKG2A complex as an inhibitory receptor recognizing this class Ib molecule by using as target a .221 transfectant selectively expressing surface HLA-E. HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1. Further studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells transfected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the inhibitory interaction was mediated by CD94/NKG2A recognizing the surface HLA-E molecule, because only antibodies directed against either HLA-E, CD94, or CD94/NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold-treated .221 cells loaded with appropriate peptides was sufficient to confer protection, resulting from recognition of the HLA class Ib molecule by the CD94/NKG2A inhibitory receptor. Consistent with the prediction that the ligand for CD94/NKG2A is expressed ubiquitously, our examination of HLA-E antigen distribution indicated that it is detectable on the surface of a wide variety of cell types.
Antigens, CD↗
Prevalence of monoclonal immunoglobulins after liver transplantation: relationship with posttransplant lymphoproliferative disorders.
BACKGROUND: A high incidence of serum monoclonal immunoglobulins (mIgs) has been described after solid organ transplantation. For transplant recipients, the prevalence of posttransplant lymphoproliferative disorders (PTLDs) has been reported to be between 2% and 6%. The relationship between the finding of serum mIg in transplant recipients and the subsequent development of PTLDs is not clearly documented. METHODS: We retrospectively analyzed all cases of mIg and PTLD that occurred in 86 liver transplant recipients who survived more than 3 months. Patients were characterized by protein electrophoresis, immunofixation electrophoresis, pre- and post-liver transplantation Epstein-Barr virus (EBV) serology, EBV presence in lymphoproliferative tissues by in situ hybridization, type of infection episodes, rejection episodes, and immunosuppressive treatment. RESULTS: Thirty-eight patients (44%) had abnormal immunofixation electrophoresis with an electrophoretic Ig peak. Twelve patients had a polyclonal Ig peak, and 26 patients had mIgs (30%). These 26 patients were divided into two groups: 13 patients had a transient mIg peak with a mean delay for normalization of electrophoresis of 2 months, and 13 patients had a permanent mIg peak. No correlation could be demonstrated between the appearance of abnormal banding and indications for transplantation, age of patients, and acute rejection rate. There was a strong correlation between occurrence of viral infections and presence of permanent mIg. Three patients with permanent mIg (23%) developed PTLD and died. CONCLUSIONS: We concluded that the prevalence of mIg after liver transplantation was 30%. Viral infections increase the risk of developing mIg. Persistence of mIg beyond 7 months may be regarded as prelymphomas necessitating a careful follow-up in these patients.
Adolescent↗
HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer.
The HLA-E class Ib molecule constitutes a major ligand for the lectin-like CD94/NKG2 natural killer (NK) cell receptors. Specific HLA class I leader sequence-derived nonapeptides bind to endogenous HLA-E molecules in the HLA-defective cell line 721.221, inducing HLA-E surface expression, and promote CD94/NKG2A-mediated recognition. We compared the ability of NK clones which expressed either inhibitory or activating CD94/NKG2 receptors to recognize HLA-E molecules on the surface of 721.221 cells loaded with a panel of synthetic nonamers derived from the leader sequences of most HLA class I molecules. Our results support the notion that the primary structure of the HLA-E-bound peptides influences CD94/ NKG2-mediated recognition, beyond their ability to stabilize surface HLA-E. Further, CD94/ NKG2A+ NK clones appeared more sensitive to the interaction with most HLA-E-peptide complexes than did effector cells expressing the activating CD94/NKG2C receptor. However, a significant exception to this pattern was HLA-E loaded with the HLA-G-derived nonamer. This complex triggered cytotoxicity very efficiently over a wide range of peptide concentrations, suggesting that the HLA-E/G-nonamer complex interacts with the CD94/NKG2 triggering receptor with a significantly higher affinity. These results raise the possibility that CD94/NKG2-mediated recognition of HLA-E expressed on extravillous cytotrophoblasts plays an important role in maternal-fetal cellular interactions.
Antigens, CD↗
The CD94/NKG2 C-type lectin receptor complex.
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Amino Acid Sequence↗
Lymphoproliferative disease after liver transplantation: primary biliary localization.
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Antigens, CD↗
Results of pancreatogastrostomy after pancreatoduodenectomy in 160 consecutive patients.
BACKGROUND: The advantages of pancreatogastrostomy over pancreatojejunostomy after pancreaticoduodenectomy are still debated. This study analyses the results of pancreatogastrostomy to identify factors that could influence immediate outcome. METHODS: During a 10-year period, 160 consecutive patients underwent a pancreatogastrostomy. There were 109 men (68 per cent) and 51 women (32 per cent) with a mean(s.d.) age of 59(10) (range 22-82) years; 27 patients were older than 70 years. The following parameters were assessed: mortality rate, morbidity, reasons for reoperation, length of hospital stay, duration of nasogastric tube and drainage. RESULTS: Hospital mortality rate was 3 per cent; overall morbidity rate was 30 per cent. The reoperation rate was 12 per cent, mainly because of bleeding at the pancreatic margin. Delayed gastric emptying occurred in 36 patients. The overall rate of pancreatic fistula was 2.5 per cent. Age, sex, indications for pancreatoduodenectomy, and the texture of the pancreatic remnant did not influence the occurrence of pancreatic fistula or delayed gastric emptying. CONCLUSION: This study confirmed that pancreatogastrostomy is a safe procedure with low mortality and morbidity rates.
Adult↗
Analysis of the effect of ppGpp on the ftsQAZ operon in Escherichia coli.
Escherichia coli loses its rod shape by inactivation of PBP2 (penicillin-binding protein 2), target of the beta-lactam mecillinam. Under these conditions, cell division is blocked in rich medium. Division in the absence of PBP2 activity is restored (and resistance to mecillinam is conferred) when the three cell division proteins FtsQ, FtsA and FtsZ are overproduced, but not when only one or two of them are overproduced. Division in the absence of PBP2 activity is also restored by a doubling in the ppGpp pool, as in the argS201 mutant. However, the nucleotide ppGpp, a transcriptional regulator of many operons, does not govern any of the five promoters of the ftsQAZoperon, as shown by S1 mapping of ftsQAZ mRNA 5' ends in exponentially growing wild-type cells in the mecillinam-resistant argS201 mutant (intermediate ppGpp level) or during the stringent response elicited by isoleucine starvation (high ppGpp level). Furthermore, the concentration of FtsZ protein is not increased in exponentially growing mecillinam-resistant argS201 cells. These results show that the ftsQAZ operon is not the ppGpp target responsible for mecillinam resistance. We are currently trying to identify those targets that, at intermediate ppGpp levels, allow cells to divide as spheres in the absence of PBP2.
Amdinocillin↗
Experimental assessment of the risk of tumor recurrence after laparoscopic surgery.
BACKGROUND: The aim of this experimental study was to evaluate the risk of tumor recurrence after laparoscopic cecal resection (LCR) of colonic carcinoma in the rat. METHODS: The experimental cancer consisted of one million cells (DHK/K12), incorporated in an extracellular matrix, placed and secured to the cecal serosa in 110 BD9 rats. Four weeks later, all animals were reoperated through a laparotomy to control tumor growth, and animals with diffuse carcinomatosis were excluded. Eligible animals were randomized either to laparoscopic cecal resection (group LCR, n = 10), to open resection (group OCR, n = 13), or to a control group without resection (group C, n = 13). Resection was always considered as macrocopically complete. All animals were killed 4 weeks after the resection to determine the tumor recurrence and quantify carcinomatosis. RESULTS: We noted diffuse carcinomatosis in 70% of rats in groups C and LCR versus 23% in group OCR (p = 0.038). For tumors noted as S- (not extending outside the serosa), diffuse carcinomatosis was observed in all animals of group C (3 of 3), in 6 of 8 in group LCR, and 0 of 6 in group OCR (p = 0.004). The rate of port site or incisional metastases was not significantly different between groups. CONCLUSIONS: These preliminary results demonstrated the deleterious impact of the laparoscopy for resection of large bowel malignancy. LCR increased significantly the incidence of a diffuse carcinomatosis even when performed for locally noninvasive tumors (S-).
Animals↗
Emergence of clinical Escherichia coli isolates with decreased susceptibility to ceftazidime and synergic effect with co-amoxiclav due to SHV-1 hyperproduction.
Between 1994 and 1996 we detected 28 out of 7054 (0.4%) clinical isolates of Escherichia coli with abnormal or reduced inhibition diameters to co-amoxiclav and ceftazidime in a disc diffusion test. The increased MIC of ceftazidime (1-32 mg/L) and the effect of synergy between this antibiotic and co-amoxiclav according to the disc diffusion test suggest the presence of an extended-spectrum beta-lactamase. However, enzymatic characterization and the nucleotide sequence confirm the hyperproduction of the SHV-1 enzyme.
Amoxicillin-Potassium Clavulanate Combination↗
Vitamin E and selenium deficiency induces expression of the ubiquinone-dependent antioxidant system at the plasma membrane.
We have used a model of dietary deficiency that leads to a chronic oxidative stress to evaluate responses that are adaptations invoked to boost cellular defense systems. Long-Evans hooded rats were fed with a diet lacking vitamin E (E) and selenium (Se) for 7 wk from weaning leading to animals deficient in both nutrients (-E -Se). In the absence of an electron donor, liver plasma membranes from these rats were more sensitive to lipid peroxidation, although they contained 40% greater amounts of ubiquinone than the plasma membranes from rats consuming diets with sufficient vitamin E and Se (+E +Se). The incubation of plasma membranes with NAD(P)H resulted in protection against peroxidation, and this effect was more pronounced in -E -Se membranes. Deficiency was accompanied by a twofold increase in redox activities associated with trans plasma membrane electron transport such as ubiquinone reductase and ascorbate free radical reductase. Staining with a polyclonal antibody against pig liver cytochrome b5 reductase, which acts as one ubiquinone reductase in the plasma membrane, showed an increased expression of the enzyme in membranes from -E -Se rats. Little DT-diaphorase activity was measured in +E +Se plasma membranes, but this activity was dramatically increased in -E -Se plasma membranes. No such increase was found in liver cytosols, which contained elevated activity of calcium-independent phospholipase A2. Thus, ubiquinone-dependent antioxidant protection in +E +Se plasma membranes is based primarily on NADH-cytochrome b5 reductase, whereas additional protection needed in -E -Se plasma membranes is supported by the increase of ubiquinone levels, increased expression of the cytochrome b5 reductase, and translocation of soluble DT-diaphorase to the plasma membrane. Our results indicate that, in the absence of vitamin E and Se, enhancement of ubiquinone-dependent reductase systems can fulfill the membrane antioxidant protection.
Animals↗
Diaphragmatic and subcutaneous seeding of hepatocellular carcinoma following fine-needle aspiration biopsy.
AIMS/BACKGROUND: We report the discovery of associated metastatic subcutaneous and metastatic diaphragmatic nodules on the needle track after fine-needle biopsy aspiration under echography, which has not yet been reported in the literature. METHODS: A 35-year-old man with non-replicating hepatitis B virus presented with a tumor that suggested hepatocarcinoma with cirrhosis. A diagnostic needle biopsy was carried out before surgery. Twelve months later, he presented with a series of four continuous metastatic diaphragmatic nodules on the inner wall lining the needle track. Surgery was performed, followed by external radiation (40 Gy). CONCLUSIONS: The risk of seeding following fine-needle biopsy aspiration of hepatocellular carcinoma can no longer be considered negligable. The real risk is probably underestimated. Even for biopsy of lesions localized to the inferior part of the liver, diaphragmatic seeding is possible. This seeding necessitates surgical resection, increasing the therapeutic morbidity of hepatocellular carcinomas. We believe that in cases where investigation of a small hepatic tumor suggests a hepatocellular carcinoma that could be resected, or for candidate patients for liver transplantation. one should not puncture the tumor. If this diagnostic biopsy is essential, then the needle track could be resected upon surgery, after cutaneous external tattooing.
Adult↗
Activated sub-populations of lymphocytes and natural killer cells in normal liver and liver grafts before transplantation.
AIMS/BACKGROUND: The anatomic structure of the liver suggests that it is a place of intense trafficking between intra-hepatic and peripheral blood compartment leukocytes. Furthermore, the liver contains a large number of passenger leukocytes that may play a role in the appearance of donor-type microchimerism after transplantation. In this study, we aimed to define the principal lymphocyte sub-populations contained in donor peripheral blood and liver grafts and in normal liver removed during minimally invasive surgery. METHODS: Liver biopsies were taken at the time of vascular clampage during liver extraction from donors in a brain dead state (GI: n=14). Normal liver biopsies were removed during minimaly invasive surgery (GII: n= 10). RESULTS: We observed evidence of the presence of lymphocytic activation associated with the two major CD8+ lymphocyte and natural killer (NK) cell populations in the two groups, with a significant increase in TCRgammadelta-bearing lymphocyte receptors between normal liver and the liver graft. CONCLUSIONS: The presence of activated leukocytes in the graft could have a fundamental role in induction of peripheral tolerance. This activation could be the result of a basic immunological response linked to the interaction of T cells and NK cells, and of secondary activation due to stress and the conditions necessary for organ removal from donors in a brain dead state.
Adult↗
[Neurophysiology of pain in tentorial irritation: description of a case secondary to medulloblastoma].
We report the case of a 32-year-old woman who complained of dull and compressing occipital pain, with unilateral radiation to the left frontal and supraorbital areas (of the sickening type). The radiological, clinical, neurosurgical and neuropathologic investigation disclosed a medulloblastoma bulging and tickening the tentorium cerebelli. This case shows how mechanical stimuli of the structures innervated by the tentorial nerve can cause pain with characteristics of trigeminal and cervical involvement.
Adult↗
A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.
Amino Acid Sequence↗
The CD94/NKG2-A inhibitory receptor complex is involved in natural killer cell-mediated recognition of cells expressing HLA-G1.
Human NK cells bear surface receptors that inhibit their cytolytic activity upon specific recognition of MHC class Ia Ags; little is known about the capacity of class Ib molecules to regulate NK cell function. We have studied the roles of different NK inhibitory receptors in recognition of the class Ib HLA-G. To this end, we analyzed the ability of an HLA-defective tumor cell line (721.221) transfected with the membrane form of HLA-G1, which contains the three external domains, to inhibit the cytolytic activity mediated by a panel of NK clones from several donors. A substantial proportion of peripheral blood NK clones appeared to be significantly inhibited by the HLA-G1-transfected cell line (referred to as .221-G1); nevertheless, no relation was observed between the expression and the function of serologically identifiable Ig-SF receptors (p58/p70) and specific recognition of .221-G1 cells. Moreover, p58 killer cell inhibitory receptor-IgG soluble fusion proteins specifically bound to 721.221 transfectants bearing their corresponding HLA-C ligands, but only a weak reactivity with .221-G1 cells was detectable. By contrast, most NK clones blocked by HLA-G1 expressed the CD94/NKG2-A inhibitory receptor, and moreover, CD94-specific mAbs reconstituted their cytolytic activity comparably to anti-HLA class I mAbs. These data support the idea that the CD94/NKG2 receptor complex is involved in the recognition of cells expressing HLA-G1.
Antibodies, Monoclonal↗
Antifibroproliferative effect of tenidap in chronic antigen-induced arthritis.
OBJECTIVE: To determine whether tenidap regulates extracellular matrix metabolism in chronic arthritis. METHODS: Antigen arthritis was induced in the knees of 30 rabbits. Animals were distributed into 3 groups: untreated, tenidap-treated, and diclofenac-treated rabbits. Three weeks after disease induction, synovial membranes were extracted and processed for histopathologic examination and detection of type I collagen (CI) and fibronectin (FN) by immunoperoxidase. Simultaneously, we analyzed the in vitro effect of tenidap on healthy synovial cell (SC) proliferation, FN expression and synthesis, and expression of transforming growth factor beta1 (TGFbeta1) messenger RNA. RESULTS: Untreated animals showed synovial lining hyperplasia, cellular infiltration at the sublining, and increased deposition of matrix proteins. These findings were not apparent in tenidap-treated rabbits, where CI and FN had the same distribution as in healthy synovial membranes. In vitro, tenidap inhibited SC proliferation (> or =25 microM) and down-regulated the expression and synthesis of FN in a dose-dependent manner (> or =1 microM). This antifibrotic effect was associated with a reduction of TGFbeta1 message. CONCLUSION: Tenidap down-regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease-modifying agent for rheumatoid arthritis.
Animals↗