Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously identified damage-recognition proteins that bind to cisplatin[cis-diamminedichloroplatinum(II), a DNA cross-linking agent]- or u.v.-modified DNA in HeLa cells [Chao, Huang, Huang & Lin-Chao (1991) Mol. Cell. Biol. 11, 2075-2080; Chao, Huang, Lee & Lin-Chao (1991) Biochem. J. 277, 875-878]. In the present study we compared damage-recognition proteins in cells expressing different sensitivities to DNA damage. An increase in damage-recognition proteins and an enhancement of plasmid re-activation were detected in HeLa cells resistant to cisplatin and u.v. However, repair-defective cells derived from xeroderma-pigmentosum (a rare skin disease) patients did not express less cisplatin damage-recognition proteins than repair-competent cells, suggesting that damage-recognition-protein expression may not be related to DNA repair. By contrast, cells resistant to DNA damage consistently expressed high levels of u.v.-modified-DNA damage-recognition proteins. The results support the notion that u.v. damage-recognition proteins are different from those that bind to cisplatin. These findings also suggest that the damage-recognition proteins identified could be used as potential indicators of the sensitivity or resistance of cells to u.v.
 ...
PMID:Damage-recognition proteins as a potential indicator of DNA-damage-mediated sensitivity or resistance of human cells to ultraviolet radiation. 154 Jan 36

Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal filament assembly and function. We have extended our earlier studies to include 8 more incidences of EHK. In half of these families, we were unable to locate a mutation within the rod domains of either K1 or K10. However, polymorphic restriction site and sequence analysis of the other families revealed a mutational hot spot within the 1A alpha-helical segment of K10. These involve Arginine to Histidine, Arginine to Cysteine and Arginine to Leucine substitutions at residue 10 of the rod domain. Interestingly, mutations in the corresponding Arginine residue in keratin K14 have been identified in patients with epidermolysis bullosa simplex. The large number of mutations found at this position in both keratins K10 and K14 suggests that other epithelia cell disorders will be discovered that are caused by the corresponding mutation in related type I keratin genes.
Hum Mol Genet 1993 Dec
PMID:A mutational hot spot in keratin 10 (KRT 10) in patients with epidermolytic hyperkeratosis. 750 30

Darier's disease is a dominantly inherited skin disorder in which there is abnormal adhesion between keratinocytes. We and others have recently mapped the disease gene to chromosome 12q23-q 24.1. In the present study we have established that the disease gene lies between the loci D12S78 and D12S79 which are 12cM apart. We have also obtained direct evidence that the disease is unlikely to result from a mutation in one of the members of the keratin gene cluster on chromosome 12q.
Hum Mol Genet 1994 Jan
PMID:The gene for Darier's disease maps between D12S78 and D12S79. 751 59

In this study, we analyzed the reliability and usefulness of the polymerase chain reaction (PCR) for the detection of T-cell receptor (TCR)gamma gene monoclonal rearrangement. We first tested for the specificity and sensitivity of this strategy, against the classical criteria of Southern blot analysis (SBA). Of the 27 samples tested, results agreed in all but two. Broader analysis of these cases demonstrated the high specificity (absence of false positives) of the PCR strategy, together with its limited sensitivity (10% of false negatives). The usefulness of this PCR approach was then tested on a panel of 28 biopsy specimens of cutaneous lymphocytic infiltrates. Monoclonal TCR gamma rearrangement was detected in seven of eight cases of early stage mycosis fungoides (MF), one of two Sezary syndrome (SS) cases, two of two non-MF T-cell lymphoma, and two of three lymphomatoid papulosis. Monoclonality was not detected in any of the 11 benign cases (parapsoriasis and inflammatory dermatosis). Results obtained with this new molecular strategy provide additional support for the hypothesis of a monoclonal origin for most early stage T-cell MF. They also suggest the heterogeneous nature of some lymphomatoid papulosis lesions. Therefore, due to the difficulty in detecting T-cell monoclonality by immunohistochemical techniques, PCR can be a useful alternative strategy to SBA. It could also be used as a complementary technique in the routine diagnosis of T-cell cutaneous infiltrates.
Diagn Mol Pathol 1994 Dec
PMID:Value of PCR detection of TCR gamma gene rearrangement in the diagnosis of cutaneous lymphocytic infiltrates. 786 39

Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal dominant skin disease characterized by impaired keratinocyte cohesion and consequent blister formation. In the present study we have used linkage analysis to map the gene for this disease to a region of chromosome 3q between D3S1589 and D3S1316. The maximum combined two point lod score in four families studied was 14.60 at theta = 0 at the D3S1290 microsatellite repeat. These findings suggest the presence of a gene not previously known to be involved in keratinocyte cohesion at this site.
Hum Mol Genet 1994 Jul
PMID:Localization of the gene whose mutations underlie Hailey-Hailey disease to chromosome 3q. 798 84

Junctional epidermolysis bullosa inversa is an autosomal recessive blistering skin disease with an ultrastructural hemidesmosome defect similar to that of the Herlitz disease, yet with a non-lethal and different course of the disease. Its delineation is based on five geographically associated Norwegian families where all parents are likely to carry a mutant EBR2A allele identical in descent. Three informative families show a lod score of +1.65 at zero recombination to a trinucleotide repeat marker in intron 20 of the laminin gamma 1 (LAMC1, previously LAMB2) locus on 1q31. The four patients of these families are all homozygous for the 146 bp LAMC1 allele present only on 5% of random Norwegian chromosomes. The daughter of a deceased patient in a fourth family carries the same 146 bp allele. This extreme association confirms that the disease locus, EBR2A, is at or closely linked to LAMC1. Localized and generalized Mitis types as well as the majority of tested families with the Herlitz type of junctional epidermolysis bullosa appeared not to be similarly linked or associated to LAMC1. The MspI and AluI RFLPs of LAMC1 showed absolute allelic association. Each of the two RFLP haplotypes showed association to either 'long' or 'short' intron 20 STR alleles.
Hum Mol Genet 1994 Aug
PMID:Junctional epidermolysis bullosa inversa (locus EBR2A) assigned to 1q31 by linkage and association to LAMC1. 798 20

Darier's disease is a rare autosomal dominant skin disorder in which there is abnormal adhesion between keratinocytes. It appears to be associated with an increased prevalence of neuropsychiatric disorders including mental retardation and epilepsy. In addition we have previously reported a family in which major affective disorder cosegregates with Darier's disease. In the present study we have localized the gene for Darier's disease to chromosome 12q23-q24.1 by linkage analysis in five British pedigrees. We obtained a maximum two point lod score of 4.29 with marker D12S84 at zero recombination fraction. All five families showed evidence of linkage between the disease gene and markers in this region. Subsequent identification of the Darier's disease gene will provide insights into normal mechanisms of cell adhesion and may be of importance in the genetic investigation of neuropsychiatric disorders as well as elucidating the pathogenesis of Darier's disease itself.
Hum Mol Genet 1993 Nov
PMID:The gene for Darier's disease maps to chromosome 12q23-q24.1. 828 Nov 34

The complex nature of epidermal tissue homeostasis is borne out by the range of diseases affecting this tissue. Indeed, mutations in proteins involved in intracellular integrity and cell-cell or cell-matrix adhesion can cause disease in an appropriate epidermal compartment. The most important realization in epidermal disease in the last two years has been that point mutations in key structural genes can result in filaments collapsing, cell cytolysis, or cell adhesion defects; and that these defects can result in severe human skin disease. Now that these associations have been made, the important next step will be to alleviate the suffering of these patients. Animal models will be an important part of these investigations; many molecules including growth factors, oncogenes, and cell adhesion molecules have been targeted to the epidermis of transgenic mice to investigate their role in disease. Such animal models should also elucidate the causes of diseases like psoriasis, a very common skin disease, the molecular basis of which remains elusive. Gene therapy involving the replacement of defective genes or local delivery of therapeutic molecules will be one of the main goals in alleviating these known epidermal diseases. Such protocols in the epidermis are aided by the relative accessibility of the skin and the presence of the "stem cells" in relatively accessible compartments. Indeed, as the last few years have shed much light on the genetic causes of epidermal disease, it is hoped that the next several years will prove as illuminating in the alleviation of these diseases.
Mol Med 1995 Jan
PMID:The latest fashions in skin disease. 852 91

The nuclear microprobe is used for element analysis of human skin cross sections, providing new insight into the physiology of normal and pathological conditions. Special interest is focused on trace elements as they work as secondary messengers or regulatory substances. The distribution of ions in normal tissues serves as reference for pathological changes. Calcium (Ca2+) is assumed to take an important role in the differentiation process of the epidermis. This paper presents new data on elemental and trace elemental distributions in skin. Samples are prepared from skin biopsies obtained from patients with skin disorder and from individuals with no records of skin disorder serving as controls. Using the nuclear microprobe, both elemental maps and quantitative depth profiles are obtained. Previous findings of abnormal Fe distribution in psoriatic skin are confirmed, and new observations of altered Zn and Ca profiles in atopic skin are reported. The relation to possible physiological/biochemical mechanisms and apoptosis ("programmed cell death") is discussed. The study is a part in a larger survey aiming at an understanding of the formation of a mature stratum corneum with a functional barrier, and its changed properties in cases of skin disorder.
Cell Mol Biol (Noisy-le-grand) 1996 Feb
PMID:Pixe analysis of pathological skin with special reference to psoriasis and atopic dry skin. 883 72

Hidrotic ectodermal dysplasia (HED), Clouston type, is an autosomal dominant skin disorder which is most common in the French-Canadian population and is characterized by hair defects, nail dystrophy and palmoplantar hyperkeratosis. Biophysical and biochemical studies conducted in HED suggested a molecular abnormality of keratins. We tested eight French-Canadian families segregating HED for linkage to microsatellite markers flanking the known keratin genes and were able to exclude linkage to these loci. Therefore, a genome-wide search for the HED gene was initiated. The first lod score above 3.00 was obtained with the marker D13S175 located in the pericentromeric region of chromosome 13q (Zmax = 8.12 at zero recombination). The cumulative lod scores were above 3.00 for six other markers in the region. A multipoint linkage analysis using the markers D13S175, D13S141 and D13S143 gave a maximum lod score of 11.12 at D13S141 with the one-lod-unit support interval spanning a 12.7 cM region which includes D13S175 and D13S141. Haplotype analysis allowed us to establish D13S143 as the telomeric flanking marker for the HED candidate region.
Hum Mol Genet 1996 Apr
PMID:The gene responsible for Clouston hidrotic ectodermal dysplasia maps to the pericentromeric region of chromosome 13q. 884 50


1 2 3 4 5 6 7 8 9 10 Next >>