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M Colonna

Publications and source records attributed to M Colonna.

At least 109 records · Page 6Linked to original sources
PubMed1997

[Empirical Bayes estimates of relative risk: principles and examples].

Most atlases, such as cancer incidence or mortality atlases, show information for geographical subunits with major differences in population size. Under such conditions, classical epidemiological mapping indexes (SIR, SMR) are unsatisfactory. Regional pattern, if they exist, cannot be shown. Empirical Bayes methods produce smoothed relative risk estimators useful for solving this problem. We present some elementary principles of these methods using cancer incidence data in the French department of Isere.

Bayes Theorem↗
PubMed1997

[Combination of induction chemotherapy with surgery and/or radiotherapy in locally advanced head and neck cancers. A retrospective analysis of a series of 125 patients].

The prognosis of locally advanced cancers of the head and the neck is pejorative, particularly when nodal involvement is present. In order to improve local control and to reduce distant failures, we have treated stages III and IV patients with induction chemotherapy. From May 1986 to November 1992, 125 patients with squamous cell carcinoma of the head and neck were treated by induction chemotherapy: cisplatine (100 mg/m2 at J1) and 5FU (1 g/m2 from J1 to J5 in continuous infusion) every 21 days subsequent local therapy consisted of surgery for patients with resectable disease, and/or radiotherapy. One hundred and nineteen patients were assessable (110 men and 9 women) with a median age of 57 years (range: 36-78). All patients had performance status inferior or equal to 2. According to the TNM of UICC classification 50 patients were stage IV (42%), 61 stage III (51%), 7 stage II (6%) and a stage I (1%). One hundred (84%) patients have received at least 3 cycles of chemotherapy. Seventy-four patients (62%, IC: 60.4-63.5) had clinical objective response (complete response (CR) or partial response (PR)) with 24 patients (20%) CR and 50 patients (42%) PR. Local therapy included surgery in 81 patients (68%) and radiotherapy alone in 42 patients (35%). Overall, 103 patients (87%) were rendered clinically disease-free by treatment on this protocol. The toxicities of cisplatine and 5-FU chemotherapy consisted predominantly of myelosuppression (5%) and renal toxicities (4%) and were moderate as described for this combination. At a median follow-up of 32 months, the median survival is 38 months (CI 95%, 18-54 months), and the median time to progression is 62 months. The oropharynx localization reached statistical significance for survival rates (Log-rank test, p = 0.02).

Adult↗
PubMed1996

Protection from lysis by natural killer cells of group 1 and 2 specificity is mediated by residue 80 in human histocompatibility leukocyte antigen C alleles and also occurs with empty major histocompatibility complex molecules.

Recognition of major histocompatibility complex class I molecules by natural killer (NR) cells leads to inhibition of target cell lysis. Based on the capacity of different human histocompatibility leukocyte antigen (HLA)-C and HLA-B molecules to inhibit target cell lysis by NK lines and clones, three NK allospecificities have been defined: NK1 and NK2 cells are inhibited by different HLA-C allotypes and NK3 cells by some HLA-B allotypes. The NK1 and NK2 inhibitory ligands on target cells correspond to a dimorphism of HLA-C at residues 77 and 80 in the alpha 1 helix: Asn77-Lys80 in NK1 and Ser77-Asn80 in NK2 inhibitory ligands. It has been reported that protection from NK1 killers depended on the presence of the Lys residue at position 80, an upward pointing residue near the end of the alpha 1 helix (and not on Asn77), whereas inhibition of NK2 effector cells required Ser77, a residue deep in the F pocket and interacting with the peptide (and not Asn80). As part of ongoing experiments to investigate the structural requirements for NK cell inhibition by HLA-C locus alleles, we also examined the effects of mutations at residues 77 and 80 on the ability of HLA-C alleles to confer protection from NK lysis. We present data confirming that the NK1 specificity depended on Lys80 (and not on Asn77); however recognition of NK2 ligands by NK cells was also controlled by the amino acid at position 80 (Asn), and mutation of Ser77 had no effect. Furthermore, bound peptide was shown to be unnecessary for the inhibition of NK cell-mediated lysis since HLA-C molecules assembled in the absence of peptide in RMA-S cells at 26 degrees C were fully competent to inhibit NK cells specifically. The implications of these data for peptide-independent recognition of HLA-C by NK receptors are discussed.

Alleles↗
PubMed1996

Tyrosine phosphorylation of a human killer inhibitory receptor recruits protein tyrosine phosphatase 1C.

Natural killer (NK) cells express killer inhibitory receptors that mediate negative regulation of NK cell cytotoxicity upon binding to MHC class I molecules on target cells. Unrelated inhibitory receptors on B cells have recently been shown to function through recruitment of phosphotyrosine phosphatase 1C (PTP-1C). Here, we show that a human killer inhibitory receptor specific for HLA-C also recruits PTP-1C after phosphorylation induced either by the pharmacological agent phenylarsine oxide or by conjugation with target cells. This recruitment is mediated by the binding of specific cytoplasmic phosphotyrosine-containing sequences to PTP-1C. These results implicate PTP-1C as a cytosolic component of the negative signaling pathway through NK cell inhibitory receptors.

Amino Acid Sequence↗
PubMed1996

A human killer inhibitory receptor specific for HLA-A1,2.

Killer inhibitory receptors (KIRs) are transmembrane glycoproteins, expressed on NK cells and a small subset of T cells, that inhibit cell-mediated cytotoxicity upon binding to polymorphic MHC class I determinants on target cells. Although human KIRs specific for HLA-C and HLA-B molecules have been characterized, none have been shown to interact with HLA-A. Here we demonstrate that a member of the KIR cDNA family, designated NKAT4, encodes a 70-kDa receptor specific for HLA-A3.

Antibodies, Monoclonal↗
PubMed1996

Human natural killer cell inhibitory receptors bind to HLA class I molecules.

To obtain direct evidence that human natural killer cell (NK) inhibitory receptors physically interact with polymorphic determinants of major histocompatibility complex class I molecules, a receptor termed NK-associated transcript-2 has been produced as a soluble fusion protein with the human IgG1 Fc portion. This soluble receptor binds specifically to HLA-C alleles with serine 77 and asparagine 80 in cell adhesion assays.

Alleles↗
PubMed1996

Natural killer clones recognize specific soluble HLA class I molecules.

Enhancement of major histocompatibility complex (MHC) class I expression leads to protection from natural killer (NK) cell recognition in several systems. MHC class I gene products are released from the cell surface and can be found in sera as soluble forms. To investigate the possible immunoregulatory role of soluble HLA (sHLA) in NK cell-target recognition, several sHLA antigens were studied for their ability to induce NK cell cytotoxicity modulation. NK cell-target recognition was inhibited by the addition of sHLA during the cytotoxicity assay. Our results indicate that sHLA molecules can down-regulate NK killing at the effector level. Moreover, different NK clones are able to specifically recognize different sHLA antigens. Kp43 molecules seem to be involved in the NK recognition of sHLA-B7.

Antigens, CD↗
PubMed1996

Severe head injuries: an outcome prediction and survival analysis.

OBJECTIVE: To identify the predictors determined early after admission and associated with unfavorable outcome or early (within 48 h) death after severe head injury. DESIGN: Prospective cohort study. SETTING: A neurosurgical intensive care unit in a university hospital. PATIENTS: 198 consecutive comatose patients hospitalized from 1989 to 1992. RESULTS: Logistic regression showed that a combination of age, best motor response score from the Glasgow Coma Scale, and hypoxia provided a good prediction model of unfavorable outcome (sensitivity = 0.93). The length of participation of survivors was 6 to 61 months (median 27.1). The Cox model demonstrated age, motor score less than 3, mydriasis, and hypoxia as poor prognosis factors. CONCLUSIONS: Clinicians can determine the odds of a good outcome from the combination of three easily measurable factors using a simple diagram constructed from logistic regression. Survival analysis showed that motor score adjusted values greater than 3 had the same prognosis.

Adult↗
PubMed1996

Protein tyrosine kinase activity in 350 T1/T2, N0/N1 breast cancer. Preliminary results.

Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of the mitogenic signal and are involved in the control of cell proliferation, differentiation, and transformation processes. PTKs can be subdivided into two major types: membrane associated PTKs consisting essentially of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogenic and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using phosphate transfer from [32P]-ATP to poly-Glu-Tyr as an artificial substrate. According to our previously reported pilot study, we chose a cut-off value of 12 pmol 32P incorporated min-1 mg-1 protein, corresponding to the median value. We found positive PTK levels (> or = 12 pmol/min/mg) to be correlated with a loss of differentiation according to Scarff-Bloom grade (p < 0.001), negative PR (p = 0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0-82), patients with a positive PTK level presented a smaller 3-year disease free survival than in the PTK negative group of patients (p = 0.07). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic factor.

Adult↗
PubMed1996

Prognostic value of quantitative cytometry in a series of 415 T1T2/N0N1/M0 breast cancer patients--preliminary results.

Identifying prognostic markers in local regional breast carcinomas remains an important challenge today. DNA content obtained by flow cytometry, has been found to be of prognostic value; results with other methods remain less clear. This report describes DNA image cytometry patterns which are assessed with respect to disease-free survival. From June 1982 to December 1992, 415 patients under 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), N0 (65.1%) N1 (34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28-75) and 58.8% of the patients were premenopausal; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade and, oestrogen receptor content were used in decision-making for adjuvant treatment: hormonotherapy (48%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was carried out on air dried smears to be analysed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index; DNA histogram, integrated optical density, DNA malignancy grade, ploidy balance. With a median follow-up of 36 months (0-105), proliferation index (P = 0.0008), DNA histogram (P = 0.0017), integrated optical density (IOD) (P = 0.018) and DNA malignancy grade (P = 0.017) had a significant prognostic value on disease-free survival estimated by the Kaplan-Meier method. When these parameters were included in a Cox proportional regression hazards model, PR (P = 0.01), Scarff-Bloom histological grading (P = 0.02), axillary clearance (P = 0.04) were significant; however, in the same model, taking into account the axillary lymph node histological status, IOD was significant for pN- patients (P = 0.03), and proliferation index (P = 0.03) was significant for pN+. Such results need to be updated with a longer median follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), should be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance.

Adult↗
PubMed1996

Natural killer cell receptors specific for MHC class I molecules.

Human natural killer cell receptors for MHC class I molecules have been recently identified by cDNA cloning. They are structurally distinct from murine natural killer cell receptors and can be either inhibitory or stimulatory. Despite structural differences, murine and human receptors are diverse and specific for distinct class I ligands. Their characterization provides insight into natural killer cell functions.

Animals↗
PubMed1996

Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation.

Recognition of major histocompatibility (MHC) class I complexes on target cells by killer cell inhibitory receptors (KIR) blocks natural killer (NK) and T cell cytotoxic function. The inhibitory effect of KIR ligation requires the phosphotyrosine-dependent association of KIR with the cytoplasmic SH2-containing protein tyrosine phosphatase SHP-1. Using a somatic genetic model, we first define a requirement for the Src family protein tyrosine kinase (PTK) Lck in mediating KIR tyrosine phosphorylation. We then investigate how KIR ligation interrupts PTK-dependent NK cell activation signals. Specifically, we show that KIR ligation inhibits the Fc receptor (FcR)-induced tyrosine phosphorylation of the FcR-associated zeta signaling chain, the PTK ZAP-70, and phospholipase C gamma. Overexpression of catalytically inactive SHP-1 (acting as a dominant negative) restores the tyrosine phosphorylation of these signaling events and reverses KIR-mediated inhibition of NK cell cytotoxic function. These results suggest sequential roles for Lck and SHP-1 in the inhibition of PTK following MHC recognition by NK cells.

Amino Acid Sequence↗
PubMed1996

Nerve regeneration through autogenous vein grafts: an SEM evaluation.

The role of autogenous vein grafts in nerve regeneration was studied in a rat model. Three groups of animals underwent autogenous vein grafting for ischiatic nerve regeneration, and were sacrificed 30, 60, and 90 days after surgery. Samples obtained were processed for S.E.M. study. Nerve regeneration consisted of two stages: the first (up to 60 days) was characterized by the presence of active endothelial cells; the second (after 60 days) by cell disappearance, with the venous wall acting as a protective conduit throughout both steps. Complete qualitative morphologic and functional studies of neural regeneration are presented, confirming previous investigations.

Animals↗
PubMed1996

The effects of scalp expansion on the cranial bone: a clinical, histological, and instrumental study.

The effects of chronic compression of the cranial bone due to progressive expansion of the scalp have been investigated. Ten patients were studied, 6 adults and 4 children, who were treated for congenital (microtia) or acquired (burns or traumatic) deformities by chronic expansion over a 2-month period. All underwent computed tomography scans of the expansion site prior to introduction of the expansion device, immediately before removal, and at 9 months after the operation. A case of postburn alopecia was lost to the study, because the patient, who had ultimated scalp expansion, did not return for flap advancement. Instead, she came back 3 months later, without the expander, which had been removed at another institution following an automobile accident. In this case, because of slower healing, we performed computed tomography scans 18 months postoperation. During the second procedure (expander removal and flap transposition), bone samples for histological examination were collected directly underneath and along the perimeter of the expanders. Macroscopically, the bone appeared thinned and had a reduced convexity. This reaction, although temporary, appeared more intense in the children and in the posttraumatic cases. Histological examination showed osteoclastic activation, bony hypotrophy, and reaction (deposition of osteoid matrix) under the device, with consequent bone resorption and remodeling. A marked hyperplasia with a hyperostotic reaction was observed around the expanders. At 9 months postoperation, in most cases, a complete normalization was confirmed by computed tomography scans. Expansion of target (fontanellar and sagittal) areas of the skull in children, as well as previous trauma to both scalp and skull should be taken into consideration as a risk factor. Further investigations are suggested.

Adolescent↗