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Biomedical subjects

M Colonna

Publications and source records attributed to M Colonna.

At least 19 recordsLinked to original sources
PubMed1992

Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene.

Human natural killer (NK) cells with the CD3- CD16+ phenotype recognize allospecificities on normal T-cell blasts. The NK-defined specificity 1 (NK-1) is recessively inherited and has been mapped to the major histocompatibility complex between the complement gene cluster and HLA-A. A gene for NK-1, however, has not been identified. Here we demonstrate that NK-1 and the recently defined NK specificity 2 (NK-2) are reciprocally associated with homozygosity for a diallelic polymorphism at amino acid positions 77 and 80 in the putative peptide-binding site of HLA-C (P less than 10(-5)). NK-cell recognition of allogeneic cells may, therefore, be controlled by HLA-C itself or by a closely linked gene(s), which dominantly prevents (resistance alleles) or recessively permits (susceptibility alleles) recognition of still-unknown target determinants.

Base Sequence↗
PubMed1992

Allelic variants of the human putative peptide transporter involved in antigen processing.

Antigen processing for presentation of peptide epitopes by major histocompatibility complex (MHC) class I molecules involves genes in the MHC class II region. Among these, PSF1 and PSF2 encode subunits of a transporter, which presumably delivers cytosolic peptides across the endoplasmic reticulum membrane to class I molecules. This close functional relationship of the transporter and class I heavy chain genes and their linkage within the MHC raise the question of whether PSF1 and PSF2, like most class I genes, are polymorphic. By single-strand conformation polymorphism analysis and DNA sequencing, a small number of amino acid sequence variants of both PSF1 and PSF2 was identified in a panel of cell lines. This limited polymorphism may contribute to a higher degree of variability at the level of the functional transporter, in which different alleles of the PSF1 and PSF2 subunits may be combined. A possible involvement of the PSF1 and PSF2 genes in susceptibility to MHC-associated diseases was examined in a preliminary assessment in patients with ankylosing spondylitis, insulin-dependent diabetes mellitus, or celiac disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Presentation of viral antigen by MHC class I molecules is dependent on a putative peptide transporter heterodimer.

Major histocompatibility complex (MHC) class I molecules present peptides derived from the endogenous protein pool to cytotoxic T lymphocytes, which can thus recognize intracellular antigen. This pathway may depend on a transporter (PSF1) to mediate entry of the cytosolic peptides into a pre-Golgi compartment where they bind to class I heavy chains and promote their stable assembly with beta 2-microglobulin. There is, however, only indirect support for this function of PSF1. Here we show that PSF1 is necessary for the efficient assembly of class I molecules and enables them to present a peptide epitope derived from endogenously synthesized viral antigen. Immunochemical and genetic data demonstrate that the PSF1 polypeptide is associated with a complementary transporter chain, which is polymorphic and is encoded by the PSF2 gene, which is closely linked to PSF1.

Antigens, Viral↗
PubMed1992

Prognostic value of epidermal growth factor receptor in a series of 303 breast cancers.

125I-EGF (epidermal growth factor) binding assay was used in tumoral specimens concerning 303 clinical T1-T2, N0-N1 breast carcinoma diagnosed between May 1987 and October 1989. Binding assay for epidermal growth factor receptor (EGFR) was performed using single saturating concentration of 125I-EGF incubated with membrane preparations in the presence or absence of unlabelled EGF. A median value of 3 fmol EGF binding capacity per mg of membrane was obtained and then selected as the threshold value to define positive and negative EGFR tumour samples. According to this definition, 50.8% of the samples were EGFR positive. We noted an inverse relationship between the expression of EGFR and that of oestrogen receptor, and a decreased EGFR expression with tumour differentiation. With a rather short median follow-up (16 months), the multivariate analysis shows that progesterone receptor appears as the only powerful predictor of disease-free survival (P = 0.002), taking into account that 70% of the patients received an adjuvant medical treatment.

Adult↗
PubMed1991

Infantile form of carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to carnitine palmitoyltransferase II deficiencies.

Reported cases of carnitine palmitoyltransferase II (CPT II) deficiency are characterized only by a muscular symptomatology in young adults although the defect is expressed in extra-muscular tissues as well as in skeletal muscle. We describe here a CPT II deficiency associating hypoketotic hypoglycemia, high plasma creatine kinase level, heart beat disorders, and sudden death in a 3-mo-old boy. CPT II defect (-90%) diagnosed in fibroblasts is qualitatively similar to that (-75%) of two "classical" CPT II-deficient patients previously studied: It resulted from a decreased amount of CPT II probably arising from its reduced biosynthesis. Consequences of CPT II deficiency studied in fibroblasts differed in both sets of patients. An impaired oxidation of long-chain fatty acids was found in the proband but not in patients with the "classical" form of the deficiency. The metabolic and clinical consequences of CPT II deficiency might depend, in part, on the magnitude of residual CPT II activity. With 25% residual activity CPT II would become rate limiting in skeletal muscle but not in liver, heart, and fibroblasts. As observed in the patient described herein, CPT II activity ought to be more reduced to induce an impaired oxidation of long-chain fatty acids in these tissues.

Blotting, Western↗
PubMed1991

Autosomal dominant deletions of the mitochondrial genome in a case of progressive encephalomyopathy.

Multiple deletions of the mitochondrial genome were found in a family in which the proband had ataxia and ketoacidotic comas. A progressive multiorgan involvement appeared in the course of the disease, and histopathological investigation demonstrated mitochondrial myopathy features with ragged red fibers. A defect of oxidative phosphorylation was found in both skeletal muscle and lymphocytes. It is surprising that various mtDNA deletions were detected both in the proband and in his healthy mother and maternal aunt but not in the rest of the maternal progeny. All the deletions were located between Cox II and cytochrome b genes, and short (4-5 bp) repeated sequences were consistently present at the boundaries of the rearrangements in different tissues. Therefore, the deletions appear not to be transmitted per se but to be inherited in a Mendelian manner, being possibly dominant. Both the Mendelian inheritance of the trait and the variety of the deletions in carriers suggest that a nuclearly encoded factor(s) might be involved in the triggering of the deletions. However, the presence of the rearrangements in healthy individuals raises the question of whether mtDNA deletions actually cause the clinical expression of the disease.

Base Sequence↗
PubMed1991

[Incidence of colonic and rectal tumors as a function of the urban and rural characteristics of the residential area in the Isère district (1979-1985), France].

From 1979 to 1985, 1443 new malignant tumors of the colon and 1017 of the rectum appear in the departement of Isère (France). Using the urban category of "Zone de Peuplement Industriel et Urbain" (Z.P.I.U), we were able to classify place of residence within 3 strata, according to the proportion of inhabitants of the rural (or urban) type. For both sexes, incidence of colon carcinomas is higher in urban categories than in rural ones. For males, incidence of rectal carcinomas is higher within areas of the rural type. Going from the urban category of the rural one, "urban" being the level of reference. Relative Risks for men are 1,0.9 and 0.6 for the colon, and 1, 1.3 and 1.2 for the rectum. For women, RR's are 1,0.8, and 0.7 for colon, and 1,1.0, and 0.8 for the rectum. Same results are described in the literature, with higher risks for colon cancers in urban areas. Our results reporting lower incidence for rectal carcinomas in Isère among men, are in contradiction with other results in the literature. This work supports the idea that epidemiology of large bowel carcinomas should focus onto segments. Second, when categories of residence allow it, it is worthwhile looking at gradients that bring more information on the relation, than the simple dichotomy: urban versus rural.

Colonic Neoplasms↗
PubMed1990

Reassessment of HLA association with celiac disease in special reference to the DP association.

Patients with the late-onset form of celiac disease have been studied for HLA association by conventional serology (DR and DQ typing) and by oligonucleotide probing with gene amplification (DP typing). Patients and controls were sampled in the Bologna area of northern Italy. Almost all patients were positive for DQw2 (94%), being DR3 positive (72%) and/or DR7 positive (65%). The proportion of DR3/7 heterozygotes in the patients was significantly increased over that expected from the Hardy-Weinberg equilibrium. No positive association with DR5 and no significant increase of DR5/7 heterozygotes were observed. Among the DP alleles reported to exhibit an association with celiac disease in other populations, only DPB3 showed a moderate increase of a borderline significance, not attributable to a linkage disequilibrium with DQw2.

Alleles↗
PubMed1990

Susceptibility or resistance to lysis by alloreactive natural killer cells is governed by a gene in the human major histocompatibility complex between BF and HLA-B.

The specificity recognized on normal allogeneic cells by a given alloreactive (1-anti-A) natural killer clone is controlled by a gene locus termed EC1. Because the EC1 locus was previously shown to be located on chromosome 6, families characterized by a recombinant major histocompatibility complex haplotype were analyzed to map this locus more precisely. The breakpoint of recombination was studied by standard HLA typing, complement typing, and restriction fragment length polymorphism analysis of a series of genes located between the complement cluster genes and HLA-B within the major histocompatibility complex region. Three of 10 families analyzed were informative. From the data obtained, the EC1 locus maps between BF and HLA-B and presumably is one of the normal genes recently described in this region.

Antigens, Differentiation↗
PubMed1990

[Can oximetry contribute to the detection of apnea? The use of a mathematical analysis of the oximetry signal].

The aim of this study was to test the efficacy of nocturnal oximetry as a means of continuous recording of SaO2 in the identification of apnoeic events in the recognition of non-apnoeic desaturation. The oscillations of SaO2 in relation to successive periods of apnoea during the course of the sleep apnoea syndrome (SAS) or with apnoeic episodes in patients with chronic airflow obstruction (BPCO) or restricted disease, were identified using a new delta index quantifying the variations of SaO2 during the night. 26 successive patients in whom there was an indication for nocturnal oximetry were included in a prospective study comparing nocturnal oximetry and polysomnography during 34 nights. In the apnoeic patients we found a strong correlation (r = .85. p. less than .01) between the apnoeic period and the delta index. In BPCO the number of apnoea was correlated with the delta index (r = .96. p. less than .01). A minimal threshold of the delta index fixed at 1.5 was satisfactory for detecting apnoea if the initial SaO2 was less than 93%. The value of the adequate for affected detection ought to be fixed at .8 (95% sensitivity) when the initial SaO2 was greater than 93%. A detection of apnoeic events thus seems possible by this method.

Apnea↗
PubMed1990

[Critical analysis of a clustering method applied to the study of geographic distribution of cancer].

Cancer registration permits to elaborate atlases that describe the spatial distribution of incidence within the registration area. The division of this area in small units is usually an administrative one, leading a wide range of unit sizes. Hence, results of indirect standardization are often difficult to interpret, due to the large variability of the observed cases. We used Huel's method (1986), which is based on the grouping of contiguous geographical zones that have the same incidence level. Here are displayed the results for cancer incidence within the "département de l'Isère" (France). We focus on method mechanisms and on the impact of the choice of the risk level.

Cluster Analysis↗
PubMed1989

Serological detection and molecular localization of allelic HLA-DP supertypic epitopes.

A DP serological allospecificity was identified using 125I-labeled preparations of HLA class II molecules isolated from cells of HLA homozygous typing cell lines, SLE (DRw6, DQw1, DPw3) and WT46 (DRw6, DQw1, DPw2), and depleted of DR molecules by absorption with an anti-DR monoclonal antibody. The specificity, provisionally called WT, was carried by class II molecules possessing the characteristics of DP molecules on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and detected primarily in DPw1, DPw3 and DPw5 cells and exceptionally in some DPw2 cells including WT46 and DPw4 cells on a large panel of DP-pretyped B cell lines mostly derived from the 10th International Histocompatibility Workshop B cell reference panel. It was apparently allelic to another DP serological specificity BUT previously defined on DP molecules isolated from cells of DPw2+ HLA deletion mutant cell line LCL 721.82. On the same cell panel; the BUT specificity was negative in all DPw1, DPw3 and DPw5 cells, and positive in all DPw2 and DPw4 cells and also in DPw2B and DPw4B cells except the cells typed WT+. This DP association pattern was similar to that of the known allelic sequences, GGPM and DEAV, in DP beta F segment, one of the six variable segments in the second exon of DP beta gene. Thus, genomic DNA from 22 B cell lines pretyped for BUT and WT specificities were enzymatically amplified for the second exon of DP beta gene by the use of locus-specific oligonucleotide primers and hybridized with 32P-labeled oligonucleotide probes corresponding to the F segment sequence variations. This oligonucleotide typing showed perfect one-to-one correlation with the BUT and WT serological typing. The typing also revealed that WT46 cells, although typed DPw2, have the DEAV sequence common to DPw1, DPw3 and DPw5.

Alleles↗