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M Tilanus

Publications and source records attributed to M Tilanus.

18 recordsLinked to original sources
PubMed2002

HLA polymorphism in Bulgarians defined by high-resolution typing methods in comparison with other populations.

In the present study we analyzed for the first time HLA class I and class II polymorphisms defined by high-resolution typing methods in the Bulgarian population. Comparisons with other populations of common historical background were performed. Most HLA-A, -B, -DRB alleles and haplotypes observed in the Bulgarian population are also common in Europe. Alleles and haplotypes considered as Mediterranean are relatively frequent in the Bulgarian population. Observation of Oriental alleles confirms the contribution of Asians to the genetic diversity of Bulgarians. The use of high-resolution typing methods allowed to identify allele variants rare for Europeans that were correlated to specific population groups. Phylogenetic and correspondence analyses showed that Bulgarians are more closely related to Macedonians, Greeks, and Romanians than to other European populations and Middle Eastern people living near the Mediterranean. The HLA-A,-B,-DRB1 allele and haplotype diversity defined by high-resolution DNA methods confirm that the Bulgarian population is characterized by features of southern European anthropological type with some influence of additional ethnic groups. Implementation of high-resolution typing methods allows a significantly wider spectrum of HLA variation to be detected, including rare alleles and haplotypes, and further clarifies the origin of Bulgarians.

Bulgaria↗
PubMed2001

The natural history of juxtafoveal and subfoveal choroidal neovascularization in high myopia.

BACKGROUND: To assess the natural history of juxtafoveal and subfoveal choroidal neovascularization in eyes with high myopia. METHODS: We retrospectively reviewed the charts of 31 patients (31 eyes) with myopia > or = 6 diopters, well-defined juxtafoveal (1-200 microm from the foveal center) or subfoveal choroidal neovascularization (CNV) on fluorescein angiography at baseline, no prior laser treatment, age < or = 55 years and presenting visual acuity (VA) > or = 20/200. Initial and final VA were compared with the Wilcoxon signed rank test. Multifactor analysis of variance was used to assess the association between baseline characteristics of the lesion and final VA. RESULTS: Twenty-two patients were females and 9 males with a median age of 44 years (range 14-55). Median diopters spherical equivalent was -11.5 (range -6, -25). Follow-up ranged from 1 to 20 years (median, 3 years). Nine eyes had juxtafoveal CNV and 22 subfoveal involvement. Median final VA (20/100) was significantly worse than median initial VA (20/50)(p = 0.02). A decrease in VA > or = 2 lines occurred in 18 eyes, whereas 8 eyes remained stable and 5 improved (4 juxtafoveal membranes and 1 subfoveal membrane). Of the 9 juxtafoveal CNV, 7 had a final VA > or = 20/40 after a median follow-up of 4 years. By contrast, only 2 of the 22 subfoveal CNV had a final VA > or = 20/40 (median, 20/100) with a median follow-up of 2.5 years. The only factor associated with better final VA was the initial location of CNV (p = 0.0000). CONCLUSION: This study confirms the poor functional outcome of subfoveal CNV in degenerative myopia with more than 70% of patients having a final VA of 20/100 or less. Juxtafoveal CNV shows a better functional prognosis. These differences should be considered when planning treatment strategies.

Adolescent↗
PubMed2000

Detection of a putative HLA-A*31012 processed (intronless) pseudogene in a laryngeal squamous cell carcinoma.

HLA class I and beta-2-microglobulin (beta2m) expression in a moderately differentiated laryngeal squamous cell carcinoma appeared to be downregulated when analyzed by immunohistochemical procedures using the monomorphic anti-HLA class I monoclonal antibody (mAb; W6/32), locus-specific (HCA2 and HC10) and allele-specific (LT129.11 and KRE501) mAbs and anti-beta2m mAbs. To reveal the molecular basis of downregulated HLA class I expression, HLA-A typing was performed on DNA derived from peripheral blood lymphocytes (PBL) and the tumor. Sequencing-based typing (SBT) revealed HLA-A*02011, 31012. In addition to HLA-A*02011, 31012 alleles, the tumor contained an HLA-A*31012 allele, which lacked all introns when sequenced from the initiation codon through exon eight. The 3' UTR region was intact up to at least 200 bp downstream. The mutant HLA-A*31012 is restricted to laryngeal tumor tissue since it was not amplified in flanking tumor-free laryngeal tissue. The mutant HLA-A*31012 shares structural characteristics with processed pseudogenes, i.e., absence of introns and an intact 3' UTR. This indicates that the mutant HLA-A*31012 allele resulted from a retroposition (reverse transcription and integration) from the processed transcript of the wild-type HLA-A*31012 allele within a clonal tumor cell. Genes Chromosomes Cancer 27:26-34, 2000.

3' Untranslated Regions↗
PubMed2000

Criteria to define HLA haplotype loss in human solid tumors.

Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta2m). The number of STR identified in the HLA region is still increasing. In this study, seven representative STR markers covering the 6p/6q arms of chromosome 6 including the HLA region and two for chromosome 15 flanking the beta2m gene, were selected as minimally required for reliable LOH studies. A multiplex polymerase chain reaction (PCR) strategy is proposed when small number of cells are available in microdissected tumor samples.

Biomarkers, Tumor↗
PubMed2000

Microsatellite analysis of microdissected tumor cells and 6p high density microsatellite analysis in head and neck squamous cell carcinomas with down-regulated human leukocyte antigen class I expression.

Down-regulated human leukocyte antigen (HLA) class I expression is frequently correlated with allelic loss at 6p21.3, which is the location of the HLA coding sequence, in head and neck squamous cell carcinomas (HNSCCs). Previously, we have demonstrated loss of heterozygosity (LOH) at 6p21.3 for at least one locus in 49% of the HNSCCs using 5 microsatellite markers spanning the 4 megabase HLA region. In the present study, the detection threshold (25%) to assign LOH was addressed by laser-assisted microdissection of tumor cells from tumors containing marginal loss. In addition, we describe high density microsatellite analysis of chromosome 6p21.3 in HNSCC with down-regulated HLA class I expression. The purpose of this study was to refine the identification of genetic alterations at 6p21.3 and to pinpoint allelic loss to individual HLA class I genes, using additional markers closely located to the HLA-A, -B, and -C loci and the transporter associated with antigen processing (TAP) genes. LOH analysis by amplification of microsatellite markers and subsequent fluorescent detection is a rapid and sensitive technique to predict HLA class I loss phenotypes in tumors. LOH can be identified at 25% relative signal reduction. Analysis of heterogeneous tumor samples and samples containing a small amount of tumor cells is facilitated by laser-assisted microdissection of tumor cells. In addition, we showed that accurate HLA LOH analysis requires application of microsatellite markers in close proximity to HLA class I and TAP genes.

Base Sequence↗
PubMed1999

Mutation in the beta 2m gene is not a frequent event in head and neck squamous cell carcinomas.

In cryostat sections of 84 head and neck squamous cell carcinomas (HNSCC) HLA class I and beta 2m expression was analysed using monomorphic and locus specific monoclonal antibodies. Loss of expression was heterogeneous and none of the tumours tested showed a total loss of HLA class I and/or beta 2m when analysed with W6/32, which recognises HLA class I determinants and anti-beta 2m MoAbs. Weak HLA class I and beta 2m expression was found in 9 tumours (11%) and heterogeneous expression was found in 2 tumours (2%). When analysed with locus-specific antibodies (HCA2 and HC10, anti-HLA-A and anti-HLA-B/C, respectively) 37 tumours (44%) showed a loss, weak or heterogeneous expression of one or both loci. Tumours showing a down-regulated HLA class I expression were analysed for mutations in either allele of the beta 2m gene by sequencing based mutation analysis (SBMA). Exon 1 and exons 2 and 3 were amplified separately by PCR using M13-tailed intron-specific primers. PCR products were sequenced in two directions. In none of the tumours mutations in the beta 2m gene were detected. In 59% of the tumours with down-regulated HLA class I expression, lost or down-regulated TAP 1 expression was found when analysed with anti-TAP 1 antibodies. This indicates an important role for TAP in down-regulation of HLA class I expression in HNSCC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas.

Loss at the chromosomal region 6p21.3 is a frequent event in head and neck squamous cell carcinomas (HNSCC). Since the human leukocyte antigen (HLA) complex is located at 6p21.3, loss of heterozygosity (LOH) of this region may provide tumour cells with an immune-escape tumour phenotype. In the present study, we have studied the correlation of HLA class I, TAP1 and TAP2 expression and LOH at 6p21.3. HLA class I and TAP1 and TAP2 protein expression was analysed by immunohistochemical procedures. A panel of 41 HNSCC with downregulated HLA class I expression was selected for LOH studies using 5 microsatellite markers located at 6p21.3 (D6S105, D6S265, D6S276, D6S273, D6S291) and 2 markers located at the chromosome 6 centromere (D6S473) and the 6p telomere (D6S277). In addition, LOH of the beta-2-nmicroglobulin (beta2m) gene was studied using 2 microsatellite markers flanking the beta2m gene (D15S126 and D15S153) and was correlated with beta2m and HLA class I expression. In 20/41 (49%) of the HNSCC, allelic loss for at least one locus at 6p21.3 was found. Loss at 15q was found in 4/10 (40%) HNSCC with downregulated beta2m expression and in 12/41 (29%) HNSCC with downregulated HLA class I expression. Our data show that downregulation of HLA class I expression is correlated with loss of chromosomal regions at 6p21.3 in HNSCC. In addition, LOH at 6p21.3 and 15q in 10 paired samples of DNA derived from the primary HNSCC, the lymph node metastases and from peripheral blood lymphocytes (PBLs) was studied. Five (5/10) primary tumours contained the same deletion as the corresponding lymph node metastases. The other cases contained deletions either in the primary tumour (3 cases) or in the lymph node metastases (1 case) or no deletions at all (1 case).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Atypical central lesions in serpiginous choroiditis treated with oral prednisone.

PURPOSE: To demonstrate the effect of oral prednisone in the treatment of atypical isolated central lesions in two patients with serpiginous choroiditis. METHODS: Two patients with a history of serpiginous choroiditis in the fellow eye developed an isolated central lesion. One patient showed combined detachment of the retinal pigment epithelium and serous detachment of the retina, while the other showed thickening of the retinal pigment epithelium and shallow detachment of the retina. Both patients were treated with 80 mg/day of oral prednisone. RESULTS: In both patients regression of the lesion and improvement of visual acuity was achieved within several days without the development of a chorioretinal scar. In one patient the lesion recurred after discontinuation of the prednisone. With continuation of a low dose of prednisone for several months definite regression of the lesion and improvement of visual acuity to near-normal values was achieved in both patients. CONCLUSION: In two patients with visual loss due to an atypical central lesion in serpiginous choroiditis, regression of the lesion without the development of a typical chorioretinal scar and subsequent improvement of visual acuity was achieved with the administration of oral prednisone.

Administration, Oral↗
PubMed1998

Description of a new DRB1*11 allele (DRB1*1132).

We describe a new DRB1*11 allele which is similar to DRB1*11011 except at codon 74, where a GCG is changed for a GTG leading to an alanine/valine substitution. This new allele was carried by a Caucasian patient suffering from rheumatoid arthritis and by her healthy daughter. The motif at codon 74 of the new DRB1*11 is not found in any other known DRB alleles, nor among the published DQA1, DQB1, DPA1 or DPB1 alleles, and therefore suggests a mechanism of point mutation.

Alleles↗
PubMed1997

A new DRB1*15 allele (DRB1*1506) identified by sequence-based typing.

A new DRB1*15 allele (DRB1*1506) was detected during the studies of the 12th International Histocompatibility Workshop within the Allele and Haplotype Society #11 which studied the DR2 and DR51 antigens. The new allele was found in four unrelated Asian Indian individuals by sequence-based typing. It has a base substitution from T to C in codon 50 at a previously considered conserved position.

Alleles↗
PubMed1993

Deletion at chromosome 16p13.3 as a cause of Rubinstein-Taybi syndrome: clinical aspects.

In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. We investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome.

Adolescent↗
PubMed1987

Oligonucleotide genotyping shows that alleles at the HLA-DR beta III locus of the DRw52 supertypic group segregate independently of known DR or Dw specificities.

Using locus- and allele-specific oligonucleotide probes, we have studied the polymorphism of the HLA-DR beta III locus within the haplotypes of the DRw52 supertypic group. DNA from a number of homozygous typing cells typed for both Dw and DR was used. The DR beta III polymorphisms, DRw52a and DRw52b, do not segregate with Dw typing, or with DR typing, indicating that the determinants responsible for Dw-defined T-cell response and for DR haplotypic recognition are not encoded by the DR beta III locus. Hence, we can conclude that these DR specificities are encoded by the other functional DR locus, DR beta I, while the DR beta III locus encodes only the supertypic product.

Base Sequence↗
PubMed1987

An experimental comparison of three methods for trephination of the cornea and the consequent variations in the configurations of the trephine openings.

We used the pig eye as an experimental model. The corneas of 51 whole eyes were trephined in a laboratory setting, using three different techniques to compare the variations in the trephine openings. Since it is difficult to assess the diameter of the hole created by trephination, we measured both the epithelial and endothelial diameters, as well as the angle between the epithelial surface and the cut of the excised corneal button, since these dimensions reflect the true shape of the hole. Trephination with either a free-standing trephine blade without a handle or with a motor-driven instrument gave the same results. However, our findings showed that the results obtained using a trephine in a holder--as is commonly used in clinical practice--were statistically significantly inferior.

Animals↗
PubMed1986

Polymorphisms within the HLA-DR3 haplotypes. I. HLA-DR polymorphisms detected at the protein and DNA levels are reflected by T-cell recognition.

HLA-DR molecules were isolated from eight different HLA-DR3 homozygous B-cell lines by immunoprecipitation with monoclonal antibodies, and they were subsequently analyzed by two-dimensional gel electrophoresis. We found that HLA-DR3 homozygous B-cell lines of consanguineous origin express two types of HLA-DR molecules. One type of HLA-DR molecule was present in all the cell lines tested, whereas the second DR molecule appears to be polymorphic. DNA isolated from the different HLA-DR3 homozygous cell lines was studied by Southern blot analysis to determine whether any DR beta restriction fragment length polymorphism could be observed. Polymorphisms detected at both the product and genomic level have been compared to each other, and their relations to the serological (HLA-DR) and cellular (HLA-D and LB-Q1) typing data will be discussed.

Antibodies, Monoclonal↗
PubMed1986

DNATYPE--a personal computer program for HLA-DR typing based upon restriction fragment length polymorphisms.

The use of specific cDNA probes and selected combinations of restriction endonucleases makes it possible to characterize specific antigens by the molecular weights of the hybridized restriction enzyme digests of DNA. We have developed a simple program suitable for personal computers which utilizes such results to deduce HLA-DR phenotypes of any nucleated cell from which DNA may be extracted.

Computers↗
PubMed1986

Reduced complexity of RFLP for HLA-DR typing by the use of a DR beta 3' cDNA probe.

The polymorphism of the HLA system has been defined by alloantisera, monoclonal antibodies, MLC reactivity, protein chemistry and RFLP patterns in DNA analysis. Typing for the alleles of HLA-DR at the DNA level as an additional typing technique is useful since any nucleated cell can be used. Moreover, it is not known whether the additional polymorphism found at the DNA level in an unambiguous serotype is of functional importance and thus needs to be included in HLA-DR typing. A main problem in DNA typing is the interpretation of the complex patterns in Southern blot analysis, especially in heterozygous individuals. Therefore we constructed subprobes from full length DR beta, DQ alpha and DQ beta cDNA to reduce the number of hybridizing fragments while retaining the discriminating capacity. The clearest differences among DR alleles have been found using the restriction enzyme PvuII and the subprobe containing the 3' untranslated region of the DR beta probe. Although further characterization is necessary to be able to type at the DNA level, the simplified patterns facilitate DNA typing in heterozygous individuals for a number of haplotypes. Interestingly, the number of fragments thus obtained corresponds with the number of genes described for DR1 to DRw8 haplotypes. Based upon the finding of common hybridizing patterns in DR3, DR5 and DRw6 it may be concluded that DR3, DR5 and DRw6 have been evolved from a common ancestor. For the same reason DR4, DR7 and DRw9 may have evolved in an identical way.

Cloning, Molecular↗