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M Colonna

Publications and source records attributed to M Colonna.

At least 91 records · Page 5Linked to original sources
PubMed1999

Cancer registry data based estimation of regional cancer incidence: application to breast and colorectal cancer in French administrative regions.

STUDY OBJECTIVE: In many countries, cancer registries cover only a small part of the national population. Cancer incidence for the rest of the country has therefore to be estimated. This can be done from mortality data using the relation between incidence and mortality observed in the cancer registry areas. Such an approach was used to study geographical variation and trend of colorectal and breast cancer incidence in France where 10% of the national population is covered by cancer registries. DESIGN: This study applies the incidence/mortality ratios of cancer registry areas to regional mortality data to obtain an estimation of cancer incidence at a given point in time. Age and period effects are included in the statistical models. MAIN RESULTS: The incidence estimations are given for 21 administrative regions and three time points (1985, 1990, 1995). The European standardised incidence rates for breast cancer ranged from 86.8 to 128.8. For colorectal cancer, these rates ranged from 48.2 to 79.6 for men, and from 32.5 to 48.8 for women. Breast cancer incidence has increased considerably between 1985 and 1995 with a higher increase in the north than in the south of France. The incidence of colorectal cancer has also increased, albeit to a lesser extent. CONCLUSION: The incidence estimation method proposed leads to regional incidence rates that are useful for planning health care services on a regional basis and may also be used to study regional differences in incidence. This method is useful when only partial incidence data are available.

Adult↗
PubMed1999

[Patterns of health care delivery and breast cancer in the department of Isère in 1955].

BACKGROUND: Caring for cancer patients is expensive, warranting verification that health care organization works in a satisfactory way. A first step of this evaluation deals with the description of the pathway followed in the health care system by the patient. METHODS: 671 breast cancer cases were diagnosed in Isère in 1995. According to the place where each treatment (surgery, chemotherapy, radiotherapy) was performed, we described pathways for the patient, either entirely private, public or mixed. Characteristics of the patient (age, place of residence), of the disease (extent of disease, way of discovery) and of the physician (general practitioner, specialist) might have influenced the choice of this pathway. We described and tested the distribution of these characteristics within the 3 groups using univariate analysis. Relative risk of being affected to the private pathway compared to the public one was computed, after adjusting for age, type of physician, extent of disease, way of discovery and sanitary area, using a multivariate analysis (logistic regression). RESULTS: In the department of Isère, the private pathway cared for 55% of breast cancers, the public one 23% and the mixed one 19%. There was no preferential recruitment according to age, physician type, presence of metastasis or of the rural or urban residence. In sanitary area number 5, characterized by an important attraction of the patients by the nearby department of Rhône, 41% of the patients were cared for the private pathway, compared to 63% in sanitary area 4, where most patients were treated in the main town of Isère: Grenoble. After early breast cancer detection with mammography instead of breast cancer screening, probability of being cared for in the private pathway was 2-fold higher (OR = 2) than in the public one. CONCLUSION: In Isère department, early breast cancer detection with mammography is in favor of the private pathway. This is not true for physician type, neither for characteristics of the patient or extent of the disease. Finally, the distance to next department of oncology or radiotherapy plays a major role.

Aged↗
PubMed1999

[Estimation of the incidence of digestive tract cancers by region].

OBJECTIVES: Information about the incidence of cancer in the national territory is a necessity for decision makers in public health. The aim of this study was to estimate for the first time the incidence of digestive tract cancers in each region of France in 1992 as well as trends in incidence between 1985 and 1995. METHODS: The incidence/mortality ratio established by sex, by age group and by localization in the departments covered by a cancer registry was applied to the mortality of each region studied. The mortality data were fit by applying a log linear model. RESULTS: The highest incidence rates of esophageal cancer were found in the North, in Brittany, Normandy and Picardy. The lowest rates were found in the regions of Midi-Pyrénées, Languedoc-Roussillon, Provence-Alpes-Côte d'Azur, Aquitaine and Poitou-Charentes. The incidence of this cancer decreased slightly between 1985 and 1995. Brittany and Normandy were also high risk regions for gastric cancer, while Provence-Alpes-Côte d'Azur, Midi-Pyrénées and Poitou-Charente were low risk regions. The incidence of gastric cancer also decreased more markedly than that of esophageal cancer. Colorectal cancer was more frequent in Alsace, Lorraine and in the North, it was less common in Provence-Alpes-Côte d'Azur, Midi-Pyrénées and Franche-Comté. The incidence of this cancer increased little over the 10 years of the study. CONCLUSION: There are regional disparities in the incidence and trends of digestive cancer incidence. These are more marked for esophageal cancer and gastric cancer than for colorectal cancer. The data supplied are of use both in the planning of health care and in the study of the causes or the prevention of digestive cancers.

Adolescent↗
PubMed1998

Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules.

Leukocyte activation can be negatively regulated by inhibitory receptors specific for MHC class I molecules. While one inhibitory receptor, Ig-like transcript 2 (ILT2), is expressed by all lymphoid and myelomonocytic cell types, other receptors display a more selective tissue distribution. Here we characterize an inhibitory receptor, termed ILT4, which is selectively expressed in monocytes, macrophages, and dendritic cells (DCs), binds classical class I molecules and the nonclassical class I molecules HLA-G, and transduces negative signals that can inhibit early signaling events triggered by stimulatory receptors. ILT4 may control inflammatory responses and cytotoxicity mediated by myelomonocytic cells and may modulate their Ag-presenting functions, focusing immune responses to microbial challenges and avoiding autoreactivity.

Animals↗
PubMed1998

NK cell natural cytotoxicity and IFN-gamma production are not always coordinately regulated: engagement of DX9 KIR+ NK cells by HLA-B7 variants and target cells.

DX9 mAb-binding killer cell-inhibitory receptors (KIR) recognize HLA-B molecules that express the Bw4 public serologic epitope. We assessed DX9+ NK cell fine specificity recognition of HLA-B7 variants and HLA-B27 alleles by 51Cr release natural cytotoxicity assays and by flow cytometry and enzyme-linked immunospot (ELISPOT) IFN-gamma synthesis and release assays. 721.221 target cell expression of Bw4+ HLA-B27 alleles specifically inhibited DX9+ NK cell natural cytotoxicity and IFN-gamma synthesis and release. A triple substitution of HLA-B7 at residues 80, 82, and 83 known to induce expression of the Bw4 serologic epitope also specifically inhibited DX9+ NK cell natural cytotoxicity and IFN-gamma responses. Single HLA-B7 amino acid substitution variants were recognized in the same decreasing rank order by DX9+ NK cells and Bw4-reactive mAbs: G83R > R82L > N80T = HLA-B7. Natural cytotoxicity inhibition was reversed by the presence of blocking DX9 mAb. Natural cytotoxicity and IFN-gamma production were coordinately regulated by a panel of HLA-B7 variants expressed on 721.221 cells, suggesting that these two effector functions are inhibited by the same KIR-mediated signaling mechanisms. In contrast, some NK cell clones killed 721.221 and K562 target cells equally well but released much more IFN-gamma in response to K562 target cells. Differential regulation of natural cytotoxicity and IFN-gamma release shows that NK cell effector functions respond to distinct signals.

Alleles↗
PubMed1998

Signaling through human killer cell activating receptors triggers tyrosine phosphorylation of an associated protein complex.

Our understanding of the biology of human natural killer (NK) cells has significantly advanced in recent years upon identification of a family of NK cell-expressed genes that encode killer cell inhibitory receptors (KIR). Individual KIR can selectively bind various HLA class I allotypes and consequently transduce inhibitory signals that block NK cell lysis of ligand-bearing target cells. A distinct subset of related and linked genes express truncated versions of KIR that are otherwise highly homologous in amino acid sequence. Interestingly, these receptors appear to transmit stimulatory signals into NK cells and have been termed killer cell activating receptors (KAR). In this report, we demonstrate that recognition of HLA-Cw3 by the p50 KAR, NKAT8, can potentiate the cytotoxic response of appropriate NK cell clones. Specific cross-linking of this KAR with a monoclonal antibody resulted in intracellular calcium mobilization, protein tyrosine phosphorylation, and phosphorylation of the MAP kinases, ERK1 and ERK2. In addition, we identified a KAR-associated disulfide-linked dimer of a 13-kDa protein that was absent in the Jurkat T cell line and is predicted to participate in these activation signaling events. Upon treatment of NK cells with pervanadate, the disulfide-linked p13 and additional proteins of 25, 30, 37 and 50-95 kDa were identified as KAR-associated tyrosine phosphoproteins. Importantly, p13 was inducibly tyrosine phosphorylated upon cross-linking of NKAT8, which strongly suggests that the associated p13 provides KAR with appropriate cytoplasmic structure to couple with tyrosine kinase-mediated signaling effectors.

Cell Line↗
PubMed1998

C-type lectin-like receptors in peptide-specific HLA class I-restricted cytotoxic T lymphocytes: differential expression and modulation of effector functions in clones sharing identical TCR structure and epitope specificity.

C-type lectin-like inhibitory receptors are heterodimers consisting of CD94 and NKG2-A-B molecules expressed on NK cells and on a subset of activated T lymphocytes. Their inhibitory effects on NK cytotoxicity and on the NK-like activity of T cell clones have been demonstrated, but no data are currently available on antigen-specific class I-restricted cytotoxic T lymphocytes (CTL). We have generated a panel of HLA-A2.1-restricted CTL clones directed against a nonapeptide derived from a melanoma-associated antigen, dopachrome tautomerase (TRP-2). All clones were CD8+ and TCR alphabeta+. About half of them expressed a CD94bright phenotype, whereas the remaining were CD94dim. Only the CD94bright CTL expressed the NKG2-A-B gene, consistent with the expression of a C-type, lectin-like, inhibitory CD94/NKG2-A-B heterodimer. Both CD94bright and CD94dim clones appeared to require similar amounts of synthetic epitope sensitizing target cells. Addition of anti-CD94 mAb resulted in a significant increase of specific killing by CD94bright, but not by CD94dim clones in the presence of suboptimal concentrations of peptide, whereas, when optimal amounts were used, the mAb did not induce a significant modulation of the cytotoxicity. Antigen-induced inward [Ca2+]i fluxes were unaffected, but an enhancement of TCR down-modulation could be observed in the presence of anti-CD94 mAb at high concentration of antigenic peptide. The analysis of the TCR-Vbeta repertoire of the CTL clones by RT-PCR and immunofluorescence revealed that all clones regardless of CD94 phenotype shared Vbeta22 expression. Most importantly, sequence analysis showed that they all expressed identical Vbeta22 TCR rearranged with Jbeta2.1 and Cbeta2. Taken together, these data indicate that different expression of functionally active lectin-like inhibitory receptors can be detected in CTL clones sharing identical TCR sequence and peptide specificity.

Amino Acid Sequence↗
PubMed1998

Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor complex.

The leukocyte receptor complex (LRC) on human chromosome 19q13.4 encompasses at least four families of related genes: immunoglobulin-like transcripts (ILT), killer cell inhibitory receptors (KIR), the leukocyte-associated inhibitory receptors (LAIR) and the Fcalpha receptor (Fc(alpha)R). We determined the genomic organization of a region of DNA spanning the junction of the ILT and KIR gene complexes. Extensive sequence data were collected for ILT3, two novel genes, ILT9 and ILT10, and one novel KIR locus (KIRCI). These loci, along with other reported sequences from the region, encoded a leader sequence split into two exons, upstream of two to four immunoglobulin (Ig) domains, each on a separate exon. Downstream of the Ig domains, however, the organization differs markedly between inhibitory and activating ILT. These data are consistent with a highly conserved gene arrangement for all superfamily members suggesting duplication of primordial sequences. ILT3 and KIRCI were in the same head-to-tail orientation as has been described for other KIR loci which may facilitate addition or loss of genes between different haplotypes.

Base Sequence↗
PubMed1998

[Prostate cancer in Isère and Tarn (France) between 1985 and 1995: evolution of therapeutic indications].

The objective is to describe the evolution of therapeutic practices of prostate carcinoma in the departements of Tarn and Isère in France for the 1985-1995 period. This retrospective study is based on patient folders for whom a prostate carcinoma has been diagnosed between 1985 and 1995. A sample of 871 patients have been included after randomisation stratified on the year and the department of the diagnostic in the files of the cancer registries of Tarn and Isère. Therapeutic practices of the prostate cancer have significantly evolved between 1985 and 1989. The rate of radical prostatectomies increased from 1986 whereas the rate of radiotherapy remained stable. This evolution has been made to the detriment of non curative treatments with the decrease of the rate of hormonotherapies. This is due to the important development of diagnostic technics which led to an earlier diagnostic of these cancers; but, the evolution of therapeutic technics and particularly of the radical prostatectomy allowed the evolution of indications for the treatment of this cancer, with the increase of the rate of radical prostatectomies and the decrease of the rate of radiotherapies at the same stage of disease evolution. For 1990 to 1995, there was no major evolution. Some indications are discussed in this disease touching old man, with a slow evolution.

Adenocarcinoma↗
PubMed1998

[Intravascular treatment of iliac aneurysms].

INTRODUCTION: We investigated the feasibility of the intravascular treatment of iliac aneurysms in patients at high perioperative risk. MATERIAL AND METHODS: January, 1996, to December, 1997, seven iliac aneurysms in 5 patients were treated using endovascular procedures. The patients were 4 men and 1 woman whose mean age was 70 years (range: 61-74 years). Four of 7 aneurysms were in the common iliac artery (2 true aneurysms and 2 anastomotic aneurysms after aortoiliac bypass) and 3 were true internal iliac artery aneurysms. Preoperative CT and arteriography were performed in all cases to define the vascular morphology of the aneurysm, including its exact diameter and length. All procedures were performed in the operating room by a team of vascular radiologists and vascular surgeons, using a portable digital RX system (Philips BV29). The femoral approach was always used, which was percutaneous under local anesthesia in 4 cases and surgical under epidural anesthesia in the other 3 cases, according to the patient's general condition and to common femoral artery morphology. Six endovascular Passager grafts were positioned in the common iliac artery using over-the-wire techniques; platinum coil embolization of the aneurysmatic internal iliac artery had been performed in 2 cases. Coil embolization of the hypogastric artery aneurysm was the only treatment in 1 case. Bilateral aneurysms were treated separately, at intervals of no less than 3 months. RESULTS: Immediate aneurysm exclusion was obtained in all cases, as confirmed at 2-20 months' follow-up in 6 cases. A displaced prosthesis needed reoperation in 1 case. No complications were observed during or early after the procedures, which were always well tolerated by the patients. DISCUSSION: The endovascular treatment of iliac aneurysms is a relatively recent procedure and thus only short- and mid-run results are currently available, which appear satisfactory in 85% of the world's literature cases. Prosthesis displacement and intimal hyperplasia are reported as the main causes of failure. Lacking long-term results, we reserve this method to selected cases. Shorter hospitalization is another advantage. CONCLUSIONS: This little invasive procedure appears suitable for high-risk patients and in the aneurysmatic complications metachronous to surgical bypass.

Aged↗
PubMed1997

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↗
PubMed1997

Major histocompatibility complex class I molecules modulate activation threshold and early signaling of T cell antigen receptor-gamma/delta stimulated by nonpeptidic ligands.

Killer cell inhibitory receptors and CD94-NKG2-A/B heterodimers are major histocompatibility complex class I-specific inhibitory receptors expressed by natural killer cells, T cell antigen receptor (TCR)-gamma/delta cells, and a subset of TCR-alpha/beta cells. We studied the functional interaction between TCR-gamma/delta and CD94, this inhibitory receptor being expressed on the majority of gamma/delta T cells. When engaged by human histocompatibility leukocyte antigen class I molecules, CD94 downmodulates activation of human TCR-gamma/delta by phosphorylated ligands. CD94-mediated inhibition is more effective at low than at high doses of TCR ligand, which may focus T cell responses towards antigen-presenting cells presenting high amounts of antigen. CD94 engagement has major effects on TCR signaling cascade. It facilitates recruitment of SHP-1 phosphatase to TCR-CD3 complex and affects phosphorylation of Lck and ZAP-70 kinase, but not of CD3 zeta chain upon TCR triggering. These events may cause abortion of proximal TCR-mediated signaling and set a higher TCR activation threshold.

Antigens, CD↗
PubMed1997

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↗
PubMed1997

A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing.

Immunoglobulin-like transcript (ILT) 3 is a novel cell surface molecule of the immunoglobulin superfamily, which is selectively expressed by myeloid antigen presenting cells (APCs) such as monocytes, macrophages, and dendritic cells. The cytoplasmic region of ILT3 contains putative immunoreceptor tyrosine-based inhibitory motifs that suggest an inhibitory function of ILT3. Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors. Signal extinction involves SH2-containing protein tyrosine phosphatase 1, which is recruited by ILT3 upon cross-linking. ILT3 can also function in antigen capture and presentation. It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells. Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.

Amino Acid Sequence↗
PubMed1997

Human histocompatibility leukocyte antigen (HLA)-G molecules inhibit NKAT3 expressing natural killer cells.

The crucial immunological function of the classical human major histocompatibility complex (MHC) class I molecules, human histocompatibility leukocyte antigen (HLA)-A, -B, and -C, is the presentation of peptides to T cells. A secondary function is the inhibition of natural killer (NK) cells, mediated by binding of class I molecules to NK receptors. In contrast, the function of the nonclassical human MHC class I molecules, HLA-E, -F, and -G, is still a mystery. The specific expression of HLA-G in placental trophoblast suggests an important role for this molecule in the immunological interaction between mother and child. The fetus, semiallograft by its genotype, escapes maternal allorecognition by downregulation of HLA-A and HLA-B molecules at this interface. It has been suggested that the maternal NK recognition of this downregulation is balanced by the expression of HLA-G, thus preventing damage to the placenta. Here, we describe the partial inhibition of NK lysis of the MHC class I negative cell line LCL721.221 upon HLA-G transfection. We present three NK lines that are inhibited via the interaction of their NKAT3 receptor with HLA-G and with HLA-Bw4 molecules. Inhibition can be blocked by the anti-NKAT3 antibody 5.133. In conclusion, NK inhibition by HLA-G via NKAT3 may contribute to the survival of the fetal semiallograft in the mother during pregnancy.

Cells, Cultured↗
PubMed1997

Cloning of novel immunoglobulin superfamily receptors expressed on human myeloid and lymphoid cells: structural evidence for new stimulatory and inhibitory pathways.

We have identified two novel human cDNA encoding transmembrane proteins of the immunoglobulin superfamily (IgSF). The two cDNA, called immunoglobulin-like transcripts 1 and 2 (ILT1 and ILT2), are expressed in myeloid and lymphoid cells and are homologous to bovine Fc gamma2R, human killer cell inhibitory receptors (KIR), human Fc alphaR, and mouse gp49. Furthermore, ILT1 and ILT2 are encoded on chromosome 19, as are Fc alphaR and KIR. While the ILT1 and ILT2 extracellular domains are homologous, the transmembrane and cytoplasmic domains differ substantially. ILT1 has an arginine within the transmembrane region, followed by a short cytoplasmic tail, similar to human Fc alphaRI and bovine Fc gamma2R. ILT2 has a long cytoplasmic tail, which contains two YxxV and two YxxL pairs similar to the immunoreceptor tyrosine-based inhibitory motifs in KIR that are known to bind the phosphotyrosine phosphatase SHP-1. These cytoplasmic features suggest that ILT1 and ILT2 may mediate novel transmembrane signals by which myeloid and lymphoid cell responses can be either activated or inhibited.

Alternative Splicing↗
PubMed1997

HLA-A typing: comparison between serology, the amplification refractory mutation system with polymerase chain reaction and sequencing.

In this study we typed HLA-A polymorphisms by a new sequence-based typing (SBT) method, which involved one PCR reaction and four sequencing reactions covering exon 2 and exon 3. This method allowed complete identification of all known HLA-A alleles and revealed the presence of a new allele, named HLA-A*2608. We also introduced sequencing of exon 4 for some samples in order to discriminate the allelic pairs that are identical in exon 2 and 3, thus improving SBT resolution. Finally, we compared the results obtained by SBT with data obtained by serological typing and the amplification refractory mutation system (ARMS-PCR). Together, our results suggest that the SBT here described provides an optimal HLA-A typing technique that may be useful in selecting donor-recipient pairs in bone marrow transplantation between unrelated individuals.

Adult↗