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  • 1
    Keywords: RECEPTOR ; CANCER ; CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; BLOOD ; CELL ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; TUMORS ; TIME ; PATIENT ; COMPLEX ; T cell ; T cells ; T-CELL ; T-CELLS ; FLOW ; BINDING ; DOWN-REGULATION ; TARGET ; NUMBER ; WOMEN ; cervical cancer ; CERVICAL-CANCER ; LIGANDS ; HLA CLASS-I ; RECEPTORS ; PERIPHERAL-BLOOD ; SERUM ; CHAIN ; ONCOLOGY ; LEVEL ; analysis ; methods ; correlation ; ENGLAND ; BETHESDA SYSTEM ; CYTOTOXICITY RECEPTORS ; G MOLECULES ; HUMAN HEPATOCELLULAR CARCINOMAS ; HUMAN-PAPILLOMAVIRUS INFECTIONS ; NATURAL-KILLER-CELL ; UNIVERSITY-STUDENTS
    Abstract: Background: Cervical cancer is the second most common cancer in women worldwide. NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with epithelial tumors. The aim of this study was to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with cervical cancer or precursor lesions with those from healthy donors. Methods: Peripheral blood with or without heparin was collected to obtain mononuclear cells or sera, respectively. Serum sMICA levels were measured by ELISA and NKG2D-expressing immune cells were analyzed by flow cytometry. Also, a correlation analysis was performed to associate sMICA levels with either NKG2D expression or with the stage of the lesion. Results: Significant amounts of sMICA were detected in sera from nearly all patients. We found a decrease in the number of NKG2D-expressing NK and T cells in both cervical cancer and lesion groups when compared to healthy donors. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing T cells; however, we did not find a significant correlation when the analysis was applied to sMICA and NKG2D expression on NK cells. Conclusion: Our results show for the first time that high sMICA levels are found in sera from patients with both cervical cancer and precursor lesions when compared with healthy donors. We also observed a diminution in the number of NKG2D-expressing NK and T cells in the patient samples; however, a significant negative correlation between sMICA and NKG2D expression was only seen in T cells
    Type of Publication: Journal article published
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  • 2
    Keywords: CELLS ; EXPRESSION ; Germany ; human ; GENE ; GENES ; PROTEIN ; DIFFERENTIATION ; TISSUE ; COMPLEXES ; DOMAIN ; SKIN ; BINDING ; MEMBERS ; DNA-BINDING ; epidermis ; human hair follicle ; FOLLICLE ; INNER-ROOT-SHEATH ; MATRIX ; RE ; hair keratins ; HOMEODOMAIN PROTEINS ; gene regulation ; EPITHELIAL KERATINS ; HOX PROTEINS ; TALE proteins
    Abstract: We previously showed that the homeodomain protein HOXC13 is involved in the expression control of the early human hair keratin genes hHa5 and hHa2, which contain specific HOXC13 binding sites in their proximal promoters. Hox specificity is generally thought to be enhanced by the interaction with members of the TALE superclass of homeodomain proteins Pbx, Meis, and Prep. Using reverse transcription PCR with total human hair follicle RNA, we demonstrated transcripts of the major TALE proteins PBX1-4, MEIS1, 2 and PREP1, 2 in the human hair follicle. In view of the presence of MEIS/PREP responsive elements in close vicinity to the HOXC13 binding sites of the hHa5 and hHa2 promoters, we determined the expression sites of these TALE proteins in the human hair follicle. We found that MEIS1, MEIS2, PREP1 and PREP2 were differentially expressed in the three layers of the inner root sheath. In addition, MEIS2 and PREP1 exhibited expression in the mid-to upper hair cortex, with PREP1 being also expressed in the dermal papilla and the connective tissue sheath of the hair follicle. In virtually all cases, the expression of these TALE proteins was exclusively cytoplasmic. Considering that in contrast, HOXC13 is expressed in the nuclei of matrix, precortex and lower cuticle cells of the hair follicle, our data suggest that despite the presence of MEIS/PREP binding sites in the hHa5 and hHa2 promoters, the HOXC13-controlled activation of these genes in the hair follicle does not seem to involve these TALE proteins as cofactors
    Type of Publication: Journal article published
    PubMed ID: 16292560
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  • 3
    Keywords: ACID, ACIDS, AMINO-ACIDS, analysis, antibodies, antibody, ASSOCIATION, chromosome, CLUSTERS, DNA, DO
    Abstract: In a search for genes overexpressed in human sexual hairs, several partial complementary DNA ( cDNA) sequences were isolated. Screening of a human scalp cDNA library with one fragment led to the isolation of a full-length cDNA clone, which showed identity to another known sequence, termed KAP24-1 (AB09693). Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon and was located ca. 86 kb away from the chromosome 21q22.1 keratin-associated protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254 amino acids, exhibited a high content of serine, proline, and tyrosine, but low cysteine content and possessed several carboxyterminal tyrosine-containing tandem decameric repeat structures. Evolutionary tree analysis showed no association to other KAP family members. In situ hybridization and indirect immunofluorescence microscopy studies using an antibody derived from KAP24.1 demonstrated specific expression in the middle/upper hair cuticle. The structure of the KRTAP24, its proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat motifs in the protein and its localization in the hair cuticle points to KAP24.1 being a novel human KAP family member
    Type of Publication: Journal article published
    PubMed ID: 17235325
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  • 4
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; GROWTH ; CELL ; Germany ; human ; PROSTATE ; TOOL ; GENE ; DIFFERENTIATION ; COMPLEX ; COMPLEXES ; MOTIFS ; FAMILY ; MARKER ; BINDING ; MEMBER ; MEMBERS ; SEQUENCE ; TYPE-1 ; TARGET ; ELEMENT ; ASSAY ; VECTOR ; MOBILITY ; PROMOTER ; ELEMENTS ; keratin ; RESPONSIVE ELEMENT ; FOLLICLE ; HAIR-FOLLICLES ; HUMAN SKIN ; CONSTITUTIVE EXPRESSION ; HUMAN TYPE-I ; ABSENCE ; MOTIF ; keratins ; HAIR FOLLICLE ; HOMOLOGY ; adrogens ; ANTIGEN GENE ; DERMAL PAPILLA CELLS ; IMMUNOCYTOCHEMICAL LOCALIZATION
    Abstract: Previous work had shown that most members of the complex human hair keratin family were expressed in terminal scalp hairs. An exception to this rule was the type I hair keratin hHa7, which was only detected in some but not all vellus hairs of the human scalp (Langbein et al, 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual hairs. Medullated beard, axillary, and pubic hairs arise during puberty from small, unmedullated vellus hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG(A)/(T)ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on hair follicles and might be a suitable tool for investigations of androgen-dependent hair disorders
    Type of Publication: Journal article published
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  • 5
    Keywords: EXPRESSION ; Germany ; human ; COMMON ; DISEASE ; RISK ; FAMILY ; SKIN ; polymorphism ; etiology ; MALES ; RISK FACTOR ; REGION ; REGIONS ; MUTATIONS ; keratin ; INDIVIDUALS ; BODY ; FOLLICLE ; HUMAN TYPE-I ; SEGMENT ; BODIES ; CORTEX ; HAIR FOLLICLE ; PROPENSITIES ; ethnic ; genodermatoses ; HHB6 ; MONILETHRIX ; shaving
    Abstract: Pseudofolliculitis barbae (PFB) is a common hair disorder characterized by a pustular foreign body inflammatory reaction that is induced by ingrown hairs of the facial and submental (barbea) regions after regular shaving. It occurs predominantly in black males, while it is rather rare and usually far less severe in Caucasian males. Black individuals have a higher propensity of developing PFB due to their genetic predisposition for curly hair which inherently possesses a much higher risk of growing back into the skin than straight or wavy hair. The PFB process is, however, not gender dependent nor restricted to the face, but can occur in any skin region once regular shaving, plucking, or other traumatic means of hair removal are instituted. Through a family study and a large-scale investigation of randomly sampled PFB-affected and -unaffected individuals, this study demonstrates that an unusual single-nucleotide polymorphism, which gives rise to a disruptive Ala12Thr substitution in the 1A alpha-helical segment of the companion layer-specific keratin K6hf of the hair follicle, is partially responsible for the phenotypic expression and represents an additional genetic risk factor for PFB
    Type of Publication: Journal article published
    PubMed ID: 15086549
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