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Biomedical subjects

M Colonna

Publications and source records attributed to M Colonna.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Adventitial cyst of the popliteal artery. Report of a case.

A case of cystic degeneration of the popliteal artery in a 58-year-old male is reported. Symptoms consisted of a claudication of abrupt onset and the correct diagnostic clue was initially given by magnetic resonance of the knee and confirmed by angiography. Treatment consisted of surgical removal of the cyst and saphenous vein angioplasty of the popliteal artery, with good anatomic and functional result at one year follow-up. Diagnostic tools and treatment of the condition are briefly discussed.

Humans↗

[Fast growing IB-IIB cancer of the uterine cervix. Apropos of 20 cases].

Twenty cases of fast growing cancer of the uterine cervix (14 IB, three IIA, three IIB FIGO), the definition of which is specified, have been reviewed and compared to a cohort of 160 cases not having this feature, to assess their outcomes. In regard to fast growing carcinomas, the median age was 41 (25-50) years and the median follow-up 22 months (8-213) as compared to 54 years (27-79) and 80 months (5-199) for the reference cohort. The comparison of the two cohorts shows only a difference of breakdown which concerns the pelvic lymph nodes status (P < 0.05, chi 2). Thirteen deaths are reported in the fast growing series instead of 54 in the other series. The 5-year overall survival is respectively 34% (13-55) versus 74% (68-82), the loco-regional free survival 58% (33-84) versus 85% (79-81) (P < 0.001), the 5-year metastasis free survival 61% (38-84) versus 84% (78-90) (P = 0.004). This particular form needs a multidisciplinary approach, and the local regional treatment has to be intensified.

Adult↗

Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells.

Cytotoxicity by natural killer (NK) cells is inhibited by major histocompatibility complex (MHC) class I molecules on target cells. This inhibition may be mediated by NK receptors with different MHC specificities. A family of four NK-specific complementary DNAs (cDNAs), designated NKATs (NK-associated transcripts), was identified that encoded related transmembrane proteins, characterized by an extracellular region with two or three immunoglobulin-superfamily domains and by a cytoplasmic domain with an unusual antigen receptor activation motif (ARAM). The distribution of these cDNAs was clonotypic and correlated with NK cell inhibition by particular class I alleles. Thus, NKAT cDNAs may encode receptors for class I molecules on NK cells.

Amino Acid Sequence↗