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Biomedical subjects

M Colonna

Publications and source records attributed to M Colonna.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1996

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↗
PubMed1996

[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↗
PubMed1995

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↗
PubMed1995

A recent increase in the incidence of prostatic carcinoma in a French population: role of ultrasonography and prostatic specific antigen.

Between 1979 and 1990, the incidence rate (World Standard) for cancer of the prostate in the region of Isère (France) increased from 22.1 to 45.0 cases per 100,000 men, although there was no concurrent increase in mortality (16.0 to 17.6 cases per 100,000 men). This represents a mean increase per year of 6.3% for incidence, compared with 1.3% (NS) for mortality. Incidence of cases with metastases at diagnosis also remained stable with time. In this area, Prostatic Specific Antigen assays began in 1987, and rectal ultrasonography was implemented in 1984, but activity peaked only in 1988. Thus, during 1986-1988, there was both an implementation of new diagnostic procedures and an increase in the incidence of prostatic carcinoma, which suggests that the latter was the result of increased detection of small latent carcinomas. This has implications for public health since apart from increasing costs, it might unduly disturb the life of otherwise healthy people.

Adult↗
PubMed1994

NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80.

Natural killer (NK) cell clones have been previously described which are inhibited by HLA-C alleles with Asn77-Lys80 (NK1-specific cells) or by HLA-C alleles with Ser77-Asn80 (NK2-specific cells). In the present work, the generation of NK cells with HLA-B-related specificities was attempted by stimulation of a Bw4 homozygous responder by a Bw6 homozygous donor. Two NK clones were found, which were inhibited by HLA-Bw4 (but not by HLA-Bw6) allotypes and by some HLA-A allotypes that share the Bw4 public epitope. Inhibition of NK cell-mediated lysis strongly correlated with the presence of an Ile residue at position 80 of the protective allele. These NK cell clones define a new specificity termed NK3.

Alleles↗