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Biomedical subjects

D Iliev

Publications and source records attributed to D Iliev.

At least 19 recordsLinked to original sources

Genomic DNA pooling for whole-genome association scans in complex disease: empirical demonstration of efficacy in rheumatoid arthritis.

A pragmatic approach that balances the benefit of a whole-genome association (WGA) experiment against the cost of individual genotyping is to use pooled genomic DNA samples. We aimed to determine the feasibility of this approach in a WGA scan in rheumatoid arthritis (RA) using the validated human leucocyte antigen (HLA) and PTPN22 associations as test loci. A total of 203 269 single-nucleotide polymorphisms (SNPs) on the Affymetrix 100K GeneChip and Illumina Infinium microarrays were examined. A new approach to the estimation of allele frequencies from Affymetrix hybridization intensities was developed involving weighting for quality signals from the probe quartets. SNPs were ranked by z-scores, combined from United Kingdom and New Zealand case-control cohorts. Within a 1.7 Mb HLA region, 33 of the 257 SNPs and at PTPN22, 21 of the 45 SNPs, were ranked within the top 100 associated SNPs genome wide. Within PTPN22, individual genotyping of SNP rs1343125 within MAGI3 confirmed association and provided some evidence for association independent of the PTPN22 620W variant (P=0.03). Our results emphasize the feasibility of using genomic DNA pooling for the detection of association with complex disease susceptibility alleles. The results also underscore the importance of the HLA and PTPN22 loci in RA aetiology.

Arthritis, Rheumatoid↗

[Pregnancy after treatment of primary sterility with zoladex in patient with essential thrombocytopenia].

We have a patient with essential /idiopathic/ thrombocitopeny and primary sterility, who becomes pregnant after medical and operative treatment. With the beginning of the menarche her menstrual cycle goes irregular with menstrual bleeding duration from 8 to 20 days, cystic ovaries, non-ovulation cycles, trombocytopeny and anemia. A laparotomy was performed twice, because of the existence of hemoperitoneum, caused by a rupture of the corpus luteum. After achieving a amenorrhoea with Zoladex treatment, a splenectomia was performed. As a result we observe a physiological recovery of the menstrual cycle, the ovulation cycle and the pregnancy. The patient's hematology and hemostaseology statuses went back to normal.

Amenorrhea↗

Transcriptional analysis of LPS-stimulated activation of trout (Oncorhynchus mykiss) monocyte/macrophage cells in primary culture treated with cortisol.

Primary immune responses to pathogen invasion are mediated by the innate immune system in which tissue macrophages play a key role. During infectious processes glucocorticoids generally may function to dampen inflammatory responses. In this study, the ability of cortisol to directly modulate the transcriptional response of rainbow trout macrophages to the cellular activator lipopolysaccharide (LPS) was investigated. The results indicate that cortisol significantly inhibits the well-described LPS-dependent induction of the expression of TNF-alpha2, a pro-inflammatory cytokine. In order to further characterize the molecular effects of LPS and the immunomodulatory role of cortisol, the in vitro macrophage response to LPS in the absence or presence of 12-h cortisol exposure was analyzed utilizing a salmonid-specific microarray platform. Genes that were stimulated or inhibited with LPS plus cortisol fell into several major functional groups. The first, a general "response" group comprising genes within ontology classes including the response to external stimuli, stress, humoral immunity and apoptosis, exhibited a significant increase after LPS stimulation, whereas suppression of this response was observed in the presence of cortisol. LPS stimulated other genes in a second group involved in cell signalling and also genes in a third group involved in the activation of transcription. Categories activated with cortisol were mainly related to various aspects of metabolism (including protein biosynthesis, binding and transport of ions) and structural proteins (mainly cytoskeleton and microtubules). The immunomodulatory action of cortisol on LPS-stimulated macrophages therefore appears more complex than simply the antagonism of LPS-induced transcriptional responses.

Animals↗

Characterization of a highly inducible novel CC chemokine from differentiated rainbow trout (Oncorhynchus mykiss) macrophages.

A full-length cDNA clone encoding a novel trout CC chemokine was identified in expressed sequence tags generated from lipopolysaccharide (LPS)-stimulated in vitro differentiated macrophages isolated from the head kidney of the rainbow trout (Oncorhynchus mykiss). The putative 101-amino-acid protein is 38% similar to Macaca mulatta CCL4 (macrophage inflammatory protein 1beta) but is also similar to several other related mammalian CC chemokines, including human Act-2. Real-time PCR and conventional RT-PCR revealed significant up-regulation of transcript levels of the trout CCL4-like mRNA in LPS-stimulated in vitro differentiated macrophages. In unstimulated trout, CCL4-like mRNA expression was detected at different levels in all tissues tested, whereas in LPS-challenged animals (6 mg/kg), CCL4-like mRNA increased in intestine, ovary and spleen at both 24 h and 72 h post-injection. In gills, CCL4-like mRNA expression was inhibited after LPS administration. Based on the highly regulated expression pattern exhibited by the trout CCL4-like mRNA, it is likely that this chemokine plays an important regulatory role in the immune response of trout.

Amino Acid Sequence↗

[Endometriosis during postmenopausal period--probable causes for its origin and development].

A very rare--casuistic--case of endometriosis is presented, which appeared ten years after surgical menopause (hysterectomy and ovariectomy) without concomitant use of hormone replacement therapy or phytoestrogens. The possibilities of endogenous production and exogenous supply of estrogens in the female organism are discussed as well as the possible causes of proliferation of endometrial lesions during postmenopausal period. When menopause is induced by surgery (a stress for the organism) without exogenous supply of estrogens (HRT, phytoestrogens, xenoestrogens) the production of suprarenal hormones, including androgens, increases. The peripheral conversion of androgens into estrogens in fat tissue is increased and implanted during hysterectomy endometrial lesions in vagina walls are stimulated.

Aged↗

[Diagnosis of eczema. Can you recognize what your patient's symptom?].

The term eczema is applied to specific non-infectious inflammatory reactions of the skin, and covers a number of etiologically highly heterogeneous conditions which, however, demonstrate common features in terms of clinical presentation and pathogenesis. Eczematous disorders account for approximately 20% of the dermatological disturbances. They include allergic, contact and irritant contact dermatitis, atopic dermatitis, seborrheic dermatitis, nummular-microbial and dyshidrotic eczema, and stasis eczema. They have a high individual and socio-economic impact, and are dependent on individual predisposition.

Dermatitis, Atopic↗

[Dermatological local therapy. How to control eczema].

The success of a topical treatment of eczema depends not only on the active agent employed, but also to a large extent on the choice of a suitable base. In the overview, therefore, not only the physical effects of the various galenic preparations (solution, shaking mixture, cream, etc.) are considered, but also the pharmacological and clinical effects of the topical corticoids and alternatives, such as, for example, bufexamac, dyes, coal tar, capsaicin, as also radiation treatment with UV-A in combination with psoralens.

Administration, Topical↗

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Amino Acid Sequence↗

BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines.

Human BRG1 is a component of the evolutionarily conserved SWI-SNF chromatin remodeling complex. BRG1 has been implicated in growth control through its interaction with the tumor suppressor pRb and may consequently serve as a negative regulator of proliferation. Postulating that BRG1 may itself be a tumor suppressor gene, we screened a panel of tumor cell lines to determine whether the gene is targeted for mutation. We report that the COOH-terminal region of BRG1 is homozygously deleted in two carcinoma cell lines, prostate TSU-Pr1 and lung A-427. In addition, biallelic inactivations of BRG1 were observed in four other cell lines derived from carcinomas of the breast, lung, pancreas, and prostate; their mutations in BRG1 included three frameshift lesions and one nonsense lesion. Point mutations were also discovered in a number of other cell lines, however in most cases any effect of these mutations on BRG1 function remains to be established. A variety of different mutations within BRG1, in several cell lines, suggest that BRG1 may be targeted for disruption in human tumors. Significantly, reintroduction of BRG1 into cells lacking BRG1 expression was sufficient to reverse their transformed phenotype inducing growth arrest and a flattened morphology. These data strongly support the model that BRG1 may function as a tumor suppressor and strengthen the hypothesis that the regulation of gene expression through chromatin remodeling is critical for cancer progression. It will be important to confirm these observations in primary tumors.

Base Sequence↗

Hand eczema in metalworker trainees--an analysis of risk factors.

The present study, as part of PROMETES (Swiss Prospective Metal Worker Eczema Study), was performed to examine risk factors for the development of occupational hand dermatitis in metal-worker trainees. Since this disease is very common, a high standard of preventive measures is necessary, especially for persons with an endogenous disposition for the development of eczema, e.g., atopics. Within the cohort of 201 healthy young men, 47 (23%) showed at least mild signs of hand eczema at 1 point of the 2.5 year observation period. Various occupational and domestic exposures, skin protection behaviour, regeneration time, and smoking habits, as well as atopic disposition, were studied with regard to their influence on the skin condition of the metalworker trainees. By multivariate analysis, we determined 3 important risk factors for the development of hand eczema in the cohort. (i) We showed once more the important influence of an atopic disposition as a major risk factor for occupational contact dermatitis. (ii) Furthermore, the results suggest that, apart from chemical irritants, mechanical factors should not be underestimated in their role as irritants to the epidermal barrier. (iii) Additionally, an insufficient amount of skin recovery time seems to support a cumulative sub-irritant effect on the skin, which may lead to irritant contact dermatitis.

Dermatitis, Occupational↗

[The European Council and health: the added value of a pan-European approach].

The Council of Europe, from its creation in 1949, has been involved in establishing regulations in various field of skills. A group of conventions and actions shows the creation of status objectives. In the field of health, the Council's actions were to improve the economic and social progress in Europe. The European Committee of Health founded in 1954, is particularly in charge of health in order to establish recommendations for the members-states such as the implementation of experts groups and the preparation of precious reports. This article exposes the main decisions.

Europe↗

Role of the atopy score and of single atopic features as risk factors for the development of hand eczema in trainee metal workers.

This study was performed as part of PROMETES (Swiss Prospective Metal Worker Eczema Study) to examine the role of atopy as a possible risk factor for the development of hand eczema in trainee metal workers. In a cohort of 201 young men without any skin problems at the start of their apprenticeship, 9.5% developed signs of dermatitis on their hands within a period of 6 months. The 2. 5-year incidence was 23%. We did not find a significantly increased risk for hand eczema in those participants with an atopic skin diathesis according to the atopy score of Diepgen et al. (Dermatosen 1991; 39: 79-83) Analysis of individual atopic signs and symptoms showed reported metal reactivity to have a significant influence on the onset of early skin damage within 6 months, whereas a history of flexural eczema appeared to be significantly related to the overall incidence over 2.5 years.

Adolescent↗

Is occupational irritant contact dermatitis predictable by cutaneous bioengineering methods? Results of the Swiss Metalworkers' Eczema Study (PROMETES).

BACKGROUND: Since identification of subjects with high eczema risk by screening tests is desirable, different skin bioengineering methods were studied for their validity as predictive measures for the development of hand eczema. METHODS: 205 metalworker trainees were followed up over 2.5 years from the beginning of their apprenticeship to observe the occurrence of hand eczema. Within the first weeks of their training they underwent a number of noninvasive biophysical tests. Transepidermal water loss, skin moisture and skin roughness were measured, and irritation tests with dimethyl sulfoxide (DMSO), sodium hydroxide (NaOH) and sodium lauryl sulfate were conducted. Sensitivity, specificity and predictive values of the performed tests and test combinations were calculated. RESULTS: None of the observed single biophysical methods can be considered a valid screening test. CONCLUSION: A combination of short irritation tests (DMSO and NaOH tests) and the measurement of skin moisture, however, allows to identify individuals at high risk for hand dermatitis with a high sensitivity, though low specificity.

Adult↗

[Effect of a baby whey bath on skin physiology parameters in young children].

Although the skin of babies is very sensitive to irritants and baby baths are widely used in child care, there have been no investigations concerning their efficacy and safety so far. In the presented work we investigate the effect of a baby bath containing 80% and after another 2 weeks of treatment with a whey baby bath. During the study all infants were bathed at a temperature between 35 and 38 degrees C for 5 to 15 min every other day. The results showed a slightly lower skin moisture, a lower skin-pH and after an initial minimal increase a reduction of skin redness values. However, none of the results were statistically significant. The tested baby bath was well tolerated by the babies' skin based on a reduction of skin-pH. In contrast to relatively aggressive soaps we found a protective effect of the tested baby bath on the acid mantle of the skin.

Baths↗

[Assessment of the quality of life of patients in dermatology].

A judgement on the patient's quality of life cannot be based solely on the information about the clinical severity of a disease. Very often there is no correlation between these parameters. It is necessary to assess the quality of life by a health status questionnaire since non-life threatening diseases common in dermatology influence the quality of life very much. The most frequently used questionnaires are the SF-36 and the Nottingham Health Profile. However, these forms do not evaluate all dermatologic patients adequately. Therefore specific tools such as the DLQI (Dermatology Life Quality Index) and Skindex have been established for dermatology. Further disease-specific questionnaires have been created to measure time related changes in dermatological patients.

Activities of Daily Living↗

Occupational protein contact dermatitis with type I allergy to different kinds of meat and vegetables.

OBJECTIVE: Even though occupational protein contact dermatitis is not an uncommon finding in occupational dermatology, reports about multiple sensitizations are rare. High-molecular-weight substances such as proteins can pass the epidermis only if it is damaged and cause a sensitization. In a high percentage of case, atopic dermatitis might be the cause of this damage but cannot be regarded as the only cause. An interesting case is presented that was carefully worked up. METHODS: Scratch, intracutaneous, and prick or prick-to-prick tests with native occupational allergens were performed as single tests. The patient was patch-tested with the European Standard Series. The determination of allergen-specific IgE was performed by ImmunoCAP. The results were subdivided into six classes. In addition, oral provocations with relevant allergens were performed. RESULTS: The skin tests showed positive type I allergies to beef, lamb, horse, and pork meat, to pork and horse blood as well as to rye and wheat flour, raw potato, and pasta. Weak positive reactions could be found for fowl, duck, goose, and turkey in intracutaneous testing. The ImmunoCAP showed elevated specific IgE values for pork meat, raw potato, and rye and wheat flour. The oral provocation did not show any systemic or skin change. CONCLUSIONS: This case report demonstrates how an initial case of contact urticaria turns into protein contact dermatitis. It shows that the diagnosis can be made by means of scratch or prick tests with native occupational allergens. The determination of allergen-specific IgE by ImmunoCAP might be helpful, but a negative result does not exclude protein contact dermatitis.

Dermatitis, Allergic Contact↗