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M Colonna

Publications and source records attributed to M Colonna.

At least 55 records · Page 3Linked to original sources

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

Lack of prognostic value of epidermal growth factor receptor in a series of 229 T1/T2, N0/N1 breast cancers, with well defined prognostic parameters.

The prognostic value of epidermal growth factor receptor (EGF-R) was prospectively assessed in a series of 229 clinical T1-T2, N0-N1 breast carcinomas diagnosed between May 1987 and October 1989. EGF-R expression was determined by measuring the specific Bmax of 125I EGF to tumor plasma membrane preparations. Tumor with a Bmax > or = 3 fmol/mg of protein were considered positive with regard to EGF-R expression. With a median follow-up of 34 months, the 3-year overall and disease-free survivals are respectively 92% and 88% for EGF-R < or = 3, and 91% and 86% EGF-R > 3 fmol, showing no significant difference, even when comparing axillary lymph node status. We did not succeed in finding an EGF-R cut-off value which might be significant in univariate analysis. Multivariate analysis of our data indicates that pT (p = 0.001), pN (p = 0.04), and Scarff-Bloom grade (p = 0.04) are the only significant predictors of disease-free survival among the parameters investigated in this study.

Analysis of Variance

Contraction and growth of deep burn wounds covered by non-meshed and meshed split thickness skin grafts in humans.

A group of 18 burned patients was excised between days 2 and 5 postburn days, while 20 patients were operated later, between days 25 and 35 postburn. After early excision the wounds covered with meshed grafts contracted to a mean wound size of 56 per cent while the wounds covered with non-meshed grafts contracted to a mean wound size of 64 per cent. After late excision wounds covered with meshed grafts contracted to a mean wound size of 40.5 per cent while wounds covered with non-meshed grafts contracted to a mean wound size of 51.5 per cent. With early excision, meshed grafts grew back to a size of 78.5 per cent while non-meshed grafts grew back to a size of 91 per cent. With late excision, meshed grafts grew back to a size of 69.5 per cent while non-meshed grafts grew back to a size of 75.5 per cent.

Adolescent

[Modulation of indications of adjuvant hormone therapy with tamoxifen in T1T2/N0N1 breast cancers. Preliminary results of a multicenter study with 695 cases].

From 1982 to 1990, patients less than 75 years, without any previous or synchonous carcinoma, suffering from an invasive breast cancer classified as T1T2/N0N1/MO according to clinical TNM staging, were enrolled in this study; 82.4% underwent a breast conservative procedure and 17.2% a modified radical mastectomy followed by a postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade, estradiol receptor content, were used to define three groups of patients. The breakdown of patients is not well balanced: 416 women were included in group I (N-, grade I II, ER+) when there was no adjuvant medical treatment, 110 in group II (N-, grade III, ER+), 169 in group III (N+ < or = 3, grade I II, ER+). Patients from the latter two groups were receiving tamoxifene, 20 mg per day for 2 years; Those women not menopaused received first a pelvic irradiation. With a median follow-up of 35 months (1-138) the overall survival is respectively for the three groups 95%, 96%, 96% (P = 0.5) and the disease free survival 86%, 93%, 90% (P = 0.1). The actuarial local regional remission rate is 94%, 97%, 99% (P = 0.07). Such results need to be updated with a longer follow-up, but they show the ability of adjuvant hormonotherapy to tailor the short term survival thanks to prognostic factors.

Adult

Human T-cell receptor (TCR) alpha/beta + CD4-CD8- T cells express oligoclonal TCRs, share junctional motifs across TCR V beta-gene families, and phenotypically resemble memory T cells.

Most human T cells express the TCR alpha/beta and either CD4 or CD8 molecules (single positive, SP); however, small numbers lack CD4 and CD8. In inbred mice, alpha/beta CD4-CD8- (double negative, DN) T cells preferentially express certain beta variable region (V beta) families and may arise via unique developmental pathways. Increased percentages of alpha/beta DN T cells have been identified in some human and murine autoimmune and immunodeficiency diseases. However, their contribution to disease pathology or normal immunity is unknown. To study the cell surface phenotype and TCR diversity of human alpha/beta DN T cells, these cells were isolated from the peripheral blood of healthy adults. The proportion of alpha/beta DN T cells expressing molecules associated with activation (HLA-DR), previous exposure to antigen (CD45RO), and cytotoxic function (CD56, CD57, and CD11b) was increased relative to SP T cells. The TCR V beta repertoire of alpha/beta DN T cells was different from that of alpha/beta SP T cells, although most major gene families were present. For example, higher proportions of V beta 11, a minor gene family in peripheral blood leukocytes, were found in most alpha/beta DN T-cell samples. In contrast to mice, no dominant V beta family was used consistently in different human individuals. Within an individual alpha/beta DN T cells possessed an oligoclonal TCR beta repertoire with conservation of several distinct junctional amino acid motifs with one joined to three different V beta genes in two individuals, suggesting that these cells have undergone a selection process driven by a limited set of ligands. The possibility that they may represent, at least in part, originally SP T cells anergized by down-modulation of CD4 or CD8 must also be entertained. Overall, this study demonstrates that human peripheral blood alpha/beta DN T cells possess unique phenotypic and TCR beta repertoire characteristics when compared with the major alpha/beta SP T cell populations and thus may serve specialized immunologic functions and/or have an unusual origin.

Adult

HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells.

Natural killer (NK) cells recognize alloantigens on normal cells. One of these alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions 77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen correlates with homozygosity for the alternative HLA-C dimorphism, which is shared by the remaining HLA-C alleles. Moreover, NK1- and NK2-specific NK cell lines can be generated by mixed leukocyte cultures in which donor and stimulator are homozygous for the alternative dimorphisms at positions 77-80 of HLA-C. In the present work, the role of HLA-C in NK cell-mediated allorecognition was directly investigated by analyzing the effects produced by transfection of several HLA-C alleles on NK sensitivity of class I-deleted mutant cell lines. Transfection of cells with HLA-C alleles encoding Asn-77-Lys-80 (including HLA-Cw4, -Cw5, and -Cw6) inhibited the lysis of the targets by NK1-specific NK cells, whereas HLA-C alleles encoding Ser-77-Asn-80 (including HLA-Cw1, -Cw7, and -Cw13) protected the targets from NK2-specific NK cells. Thus, HLA-C alleles are the dominant inhibitory ligands that protect targets from lysis by these allospecific NK cells.

Alleles

Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C.

The cytotoxicity of human natural killer (NK) cells is modulated by the major histocompatibility complex human leukocyte antigen (HLA)-C molecules on the surface of the target cell. Alloreactive NK cells specific for the NK-1 alloantigen could be reproducibly generated from individuals that were homozygous for HLA-C with asparagine at residue 77 and lysine at residue 80 [HLA-C(Asn77,Lys80)] by stimulation with target cells that were homozygous for HLA-C(Ser77,Asn80); the reciprocal stimulation yielded NK cells specific for the NK-2 alloantigen. However, neither homozygous target cell stimulated the generation of alloreactive NK cells from heterozygous individuals. Thus, these data reveal an unanticipated difference between human NK alloreactivity defined by this system and murine "hybrid resistance."

Alleles

Linkage disequilibrium between TAP2 variants and HLA class II alleles; no primary association between TAP2 variants and insulin-dependent diabetes mellitus.

The TAP1 and TAP2 genes, located in the HLA class II region, encode subunits of a peptide transporter. Both genes display limited genetic variability; four different nucleotide substitutions have been found in the TAP2 gene. Here studies on linkage disequilibrium between TAP2 variants and HLA class II alleles are reported, in an attempt to evaluate whether TAP2 variants are associated with insulin-dependent diabetes mellitus (IDDM). As reported previously, a significant decrease of homozygosity for TAP2 alleles encoding alanine at residue 665 (665 Ala) and glutamine at 687 (687 Gln) paralleled by an increase in homozygosity for TAP2 alleles encoding threonine at residue 665 (665 Thr) and a stop codon at 687 (687 Stop), was found in both Finnish and Norwegian IDDM patients compared to random controls. However, a strong linkage disequilibrium between these TAP2 polymorphisms and given HLA-DR and -DQ genes was observed among healthy controls. The frequent 665 Thr and 687 Stop variants were in linkage disequilibrium both with the DR4-DQ8 and the DR3-DQ2 haplotypes, haplotypes which are strongly associated with IDDM. In contrast, the DR1-DQ5 and DR13-DQ6 (e.g. DQB1*0603) haplotypes, which are decreased among IDDM patients, were associated with the 665 Ala and 687 Gln variants. Thus, when DR- and DQ-matched patients and controls were compared, associations of the investigated TAP2 variants and IDDM were no longer detectable. These data, therefore, indicate that the associations previously found between certain TAP2 variants and IDDM are secondary to a primary association between this disease and particular DQ alpha beta heterodimers.

ATP Binding Cassette Transporter, Subfamily B, Mem

Haplotypic variation of the transporter associated with antigen processing (TAP) genes and their extension of HLA class II region haplotypes.

Stable cell surface presentation of HLA class I molecules requires active transport of antigenic peptides across the endoplasmic reticulum by products of two genes, TAP1 and TAP2, which map in the major histocompatibility complex class II region. Alleles of each gene are derived from a combination of variable sites at each locus. In this study, TAP1 and TAP2 alleles were identified in homozygous typing cell (HTC) lines, allowing resolution of specific haplotypes in conjunction with the highly polymorphic HLA class II region haplotypes. Three alleles at each TAP locus were found from which eight haplotypes could be assigned. Determination of TAP1 and TAP2 alleles in cell lines homozygous at DR, DQ, and DP created eight additional haplotypes beyond the number observed with these class II genes alone. Complete analysis of DR, DQ, TAP, and DP genotypes in 66 HTCs resulted in the following groups: 1) 46 homozygotes; 2) nine homozygous at DR, DQ, and TAP, but heterozygous at DP; 3) four homozygous at DR, DQ, and DP, but heterozygous at one or both TAP genes; 4) four homozygous at DR and DQ, but heterozygous at TAP and DP; and 5) three complex genotypes heterozygous at DP, TAP, and at least one of DQA1, DQB1, or DRB1 loci. TAP1 and TAP2 genes map in an area of frequent recombination. TAP alleles were determined in five DQB1, DPB1 recombinant individuals, three of which were informative. Recombination was found between DQB1 and the TAP loci in two individuals and between TAP and DPB1 in the other individual.

ATP Binding Cassette Transporter, Subfamily B, Mem

Protein tyrosine kinase activity as a prognostic parameter in breast cancer, a pilot study.

Protein tyrosine kinase (PTK) activity was assayed in cytosolic extracts from normal breast tissue, benign tumors, and 84 T1-T2, N0-N1 M0, breast carcinomas. Normal breast tissue extracts yielded an average value of 1.9 +/- 1.1 pmol 32P incorporated/min/mg protein, whereas a mean of 12.5 +/- 6.1 was obtained for cancer samples. With a median follow-up of 34 months, in the series of 40 patients classified N-, PTK positive patients presented a significantly smaller 3-year disease free survival than the PTK negative ones. Multivariate analysis shows that PTK activity emerges as a potential prognostic factor in breast cancer (p = 0.02). These preliminary results will be updated on a bigger cohort of patients.

Adult

Post-carotid endarterectomy hyperperfusion syndrome: preliminary observations for identifying at risk patients by transcranial Doppler sonography and the acetazolamide test.

Patients at risk of hyperperfusion syndrome after carotid endarterectomy are often severely hypertensive and have a high grade internal carotid artery stenosis with disordered autoregulation due to a loss of reserve capacity (RC). Cerebral RC can be studied by sophisticated and expensive technical devices (SPECT, PET). Recently it has been demonstrated that the transcranial Doppler (TCD) and acetazolamide provocation test can be used to assess RC. From September 1991 to January 1992, 36 patients were studied by the TCD and acetazolamide test prior to carotid endarterectomy to identify patients at high risk of the hyperperfusion syndrome. Preoperatively, the patients were studied by TCD at rest and after vasolidation with acetazolamide 1 g intravenously (i.v.). Mean blood flow velocity on the middle cerebral artery (MCAv) was recorded for the following 20 min at 5 min intervals. MCAv at rest was 49 +/- 17 cm/s. After acetzaolamide infusion in 33 patients (92%), the mean MCAv was 62 +/- 19 cm/s with an increase of 19 +/- 13 cm/s (normal RC). In three patients (8%), the mean MCAv was 43 +/- 22 cm/s with a decrease of -6 +/- 3 cm/s with respect to base values (reduction of RC). (t = 3.30; p = 0.0022). All these patients were hypertensive (BP > 180/100 mmHg) and had a carotid artery stenosis > 90%. Postoperatively, the three patients with reduction of RC complained of homolateral headache. TCD showed a mean MCAv of 67 +/- 17 cm/s, an increase compared to the preoperative rest values of 17 +/- 8 cm/s, the 33 patients with normal RC showed a mean change in MCAv -2 +/- 12 cm/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide

The selection for shunting in patients with severe bilateral carotid lesions.

Patients with severe bilateral carotid lesions (stenosis and contralateral internal carotid occlusion) are at high risk of having a stroke, and carotid endarterectomy has been proposed as the best treatment. In spite of improvements in surgical technique, this operation is still associated with significant perioperative complications (5-13%) which are frequently (up to 40%) correlated with intolerance to internal carotid artery clamping. For this reason, intraoperative cerebral monitoring able to accurately detect ischaemia during surgery would be useful. Reviewing our experience from the last 7 years in 74 patients operated on for stenosis and contralateral occlusion of the internal carotid artery, we found a 1.3% neurological morbidity and 1.3% mortality rate. Presenting symptoms included focal transient ischaemia attacks (TIAs) in 57 patients, stroke in 16 patients and two patients were asymptomatic. Half of these patients (37) were operated on under general anaesthesia with electroencephalogram (EEG) monitoring, stump pressure measurement and selective shunting. In this group, two patients (5.4%) sustained a postoperative stroke, one of which was fatal. The remaining 37 patients were operated on under local-regional anaesthesia with selective shunting on the basis of neurological deficit onset or loss of consciousness during the test clamp. There were no postoperative neurological complications in this group but one patient died of acute myocardial infarction on the 6th postoperative day. This experience suggests that it is possible to perform carotid endarterectomy in patients with severe bilateral lesions with a postoperative complication rate similar to that in patients with less complicated obstructive lesions if accurate intraoperative cerebral monitoring is used.

Adult

[Sexual dimorphism of deciduous teeth in medico-legal identification].

Sexual identification of immature skeletal remains is still a difficult problem to solve in Forensic Anthropology. For this reason we have attempted to use sexual dimorphism of deciduous teeth. Mesial-distal and vestibular-palatal crown diameters of maxillary deciduous molars were obtained from 80 (40 male, 40 female) Apulian (southern Italian) children with age included from 3 to 11. In addition, for each tooth, three dental indexes were calculated from crown measurements. Data, so obtained, were separately analyzed using discriminant functions. The results revealed that the combinations of crown diameters were not able to give significant functions for "sexing" immature skeletal remains. Only specific combinations of dental indexes gave significant results. The best function, obtained by the association of crown index of 54, 55, 65 and crown module of 64, allow correct sex determination of prepuberal human skeleton with a misclassification of 20%.

Child

[Determination of skeletal sex using discriminant analysis of ulnar measurements].

Twelve ulnar measurements take on a series of 80 skeletons (40 male, 40 female) of a known Southern Italian population have been used in 9 combinations to produce discriminant functions for skeletal sex determination. The highest percentage of correct sex classification (95%) was obtained by the association of the minimum circumference and the maximal length. Using other four discriminant functions sex is correctly identified in 93.75% of the sample; in addition two of these functions, obtained by the associations of: minimum circumference and distal epiphyseal breadth, height of proximal articular surface, superior breadth and corio-olecranic distance, allowed to have a sex determination even by fragmented ulnae. For each discriminant function proposed, coefficients of discrimination, section points, male and female centroid and the percentage of misclassification are reported. Practical applications of this method will be certainly of aid in sexual identification in case of forensic interest.

Adult

[Surgical treatment of gynecomastia. Indications and methods].

In this paper the authors present their experience in the surgical treatment of gynecomastia; the different surgical techniques used (liposuction, adenomammectomy, liposuction associated with adenomammectomy) are compared bilaterally 42 patients (37 patients) were affected of bilateral gynecomastia, 5 patients monolateral only (age 18-38 years) were treated in the Department of Plastic and Reconstructive Surgery-Ca' Granda Hospital of Milan, from 1985 to 1991. 12 patients were treated by the adenomammectomy technique; plain liposuction alone was used in 4 patients only. The associated method (liposuction and adenomammectomy) was performed on 26 patients. The results obtained suggest that the associated method is usually the most effective, because esthetic results are excellent and post-operative complications are very low. In selected cases however the other techniques should be preferred, and the criteria of selection are discussed.

Adolescent

Blood brain barrier breaking. Is still an absolute contraindication to early surgical reperfusion of the brain?

In the early treatment of the patients with cerebrovascular insufficiency due to internal carotid artery stenosis, the presence of a cerebral infarct and especially the blood brain barrier breaking (BBB) are considered by many as a contraindication to early reperfusion by carotid endarterectomy (CEA). Generally, it has been recommended to differ the operation at least for 4-6 weeks because of the high risk to convert an ischemic infarct into an hemorrhagic one. On the other hand, because unfavorable natural history has been reported as for the progressing unstable neurological deficit as for the minor recent strokes, respectively by Millikan and Dosik, it seem to be justified a more aggressive management with the aim of: 1) eliminating the stenosis as embolic source of emboli; 2) obtaining early brain reperfusion to increase the probability of good recovery. Some previous experiences reported in the literature demonstrated satisfactory results of early reperfusion even in presence of BBB. The Authors present 4 cases of early CEA in patients with BBB. After the CT scan the patients have been submitted preoperatively to non invasive tests (duplex scanning and transcranial Doppler sonography) to assess the presence of the internal carotid artery stenosis and the viability of the intracranial cerebral arteries with special regard to the middle cerebral artery. All the patients underwent CEA in loco-regional anesthesia and particularly systemic blood pressure was carefully monitored and any hypertensive status was early corrected by prompt antihypertensive therapy (i.v. nitrates and or calcium blocking agents).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged