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)

To evaluate the specificity and applicability to the study of human tumor cells of the reverse transcription (RT) in situ PCR and RT polymerase chain reaction (PCR) in situ hybridization techniques, we examined five melanoma cell lines and five nonmelanoma lines for tyrosinase mRNA using primers specific for tyrosinase. Each procedural step was optimized and minutely controlled, and results from the in situ techniques and solution-phase RT-PCR were compared. All melanoma lines showed a specific pattern of perinuclear cytoplasmic reaction not seen in nonmelanoma lines. There was exact agreement between the results from the RT in situ PCR and RT-PCR in situ hybridization techniques and those from solution-phase RT-PCR. Ribonuclease digestion abolished cytoplasmic staining, as did omission of the reverse transcriptase step. Nuclear staining was seen in melanoma and nonmelanoma lines, apparently as a result of DNA synthesis from repair-replication and mispriming or nonspecific amplification. Neither high concentrations of deoxyribonuclease nor long incubation periods abolished this effect completely. Demonstration of cytoplasmic mRNA by RT in situ PCR and RT-PCR in situ hybridization specifically identifies cells of melanocytic lineage.
Diagn Mol Pathol 1997 Feb
PMID:Demonstration of cytoplasmic tyrosinase mRNA in tissue-cultured cells by reverse transcription (RT) in situ polymerase chain reaction (PCR) and RT PCR in situ hybridization. 902 34

To gain insight into how tumor antigens are generated and presented, a panel of peptides corresponding to melanoma-specific T cell epitopes were tested for their transport capacity by the transporter associated with antigen processing (TAP). The melanoma epitopes exhibited differential capacities to be transported by TAP in streptolysin O-permeabilized cells, as well as differential competition for peptide binding to TAP. The data indicate that some melanoma-specific epitopes are good substrates for TAP, while others are poor substrates for TAP. One of the epitopes, derived from tyrosinase, was transported into the endoplasmic reticulum (ER), in spite of being a poor competitor for reporter peptide transport and for peptide binding. These results suggest that the melanoma antigens follow distinct pathways for presentation, along the MHC class I pathway.
Mol Immunol 1996 Oct
PMID:Binding and transport of melanoma-specific antigenic peptides by the transporter associated with antigen processing. 907 Jun 64

Dopamine acts, under appropriate conditions, as a selective neurotoxin. This toxicity is attributed to the autoxidation of the neurotransmitter into a reactive quinone that covalently modifies cellular macromolecules (i.e. proteins and nucleic acids). The oxidation of the catecholamine to a quinone is greatly accelerated by the enzyme tyrosinase. There is controversy, however, as to whether or not tyrosinase is expressed in human brain. In the present study, RT-PCR was utilized to demonstrate the presence of tyrosinase mRNA in post-mortem human brain tissues. Using gene-specific amplification primers, specific tyrosinase amplicons were detected following analysis of RNA from substantia nigra of four individuals. Analysis of cerebellar RNA from the same individuals produced no amplification products. Control reactions performed in the absence of reverse transcriptase failed to generate PCR products for any tissue tested. Three amplicons were subjected to direct DNA sequencing and all proved to be identical with tyrosinase sequences, thus obviating the possibility of amplification of a related gene. It is clear, therefore, that the tyrosinase gene is expressed in the human substantia nigra, lending support to previous studies describing tyrosinase-like activity and immunoreactive protein in the brain. This enzyme could be central to dopamine neurotoxicity as well as contribute to the neurodegeneration associated with Parkinson's disease.
Brain Res Mol Brain Res 1997 Apr
PMID:Tyrosinase mRNA is expressed in human substantia nigra. 910 85

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease accounting for >2% of the congenitally deaf population. It is characterized by deafness in association with pigmentary anomalies and various defects of neural crest-derived tissues. At least four types are recognized (WS1, WS2, WS3 and WS4) on the basis of clinical and genetic criteria. Two previously described families seemed to delineate a new subtype characterized by WS2 in conjunction with ocular albinism (OA). Since mutations in the MITF gene are responsible for some instances of WS2, we screened for mutations in one of the WS2-OA families and discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated with compound heterozygosity for a mutant TYR allele and the TYR(R402Q) allele, a functionally significant polymorphism that is associated with moderately reduced tyrosinase catalytic activity. In this family, all of the individuals with the OA phenotype are either homozygous or heterozygous for TYR(R402Q), and heterozyous for the 1 bp deletion in MITF This suggests that the WS2-OA phenotype may result from digenic interaction between a gene for a transcription factor (MITF) and a gene that it regulates (TYR).
Hum Mol Genet 1997 May
PMID:Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). 915 38

Despite the importance of the substrate 4-hydroxyanisole in melanoma therapy, the kinetics of its oxidation catalyzed by tyrosinase has never been properly characterized. This approach is reported here for the first time. The applicability to 4-hydroxyanisole of the reaction mechanism of tyrosinase previously proposed for other monophenols has been corroborated. The Michaelis constant for the oxidation of 4-hydroxyanisole catalyzed by mushroom tyrosinase was (62 +/- 1.5) microM at pH 7 and increased when the pH decreased, reaching a value of (195 +/- 5) microM at pH 5.5. However the maximum steady-state rate, whose value was (0.54 +/- 0.01) microM/min, did not change with the pH. The apparent catalytic constant was (184 +/- 5) s-1, around twenty three times higher than that previously described for L-tyrosine (8 s-1).
Biochem Mol Biol Int 1997 May
PMID:Kinetic study of the oxidation of 4-hydroxyanisole catalyzed by tyrosinase. 916 22

We analyzed the tyrosinase (TYR) gene of 12 Korean patients with various types of oculocutaneous albinism (OCA). We identified five different mutations in the TYR gene in 4 patients with severe OCA and in 2 patients with mild OCA, but found no mutations in the 6 patients with mild OCA phenotypes. Among the 5 mutations, a frameshift mutation, P310insC, was detected most frequently (allele frequency = 0.5), and the other mutations were found less frequently, two of which, L288delT and IVS2-7t-->a,-10(-)-11deltt, are novel. This study may provide valuable information for the molecular diagnosis of and accurate genetic counseling for OCA1 in Koreans and perhaps other Asian groups.
Mol Cells 1997 Apr 30
PMID:Prevalent and novel mutations of the tyrosinase gene in Korean patients with tyrosinase-deficient oculocutaneous albinism. 916 30

We have previously shown that all CBA/J mice exposed to 4-nitroquinoline-1-oxide (4NQO) eventually develop oral cavity squamous cell carcinomas, and two-thirds of these tumors have Ha-ras-1 (Hras1) point mutations at codon 12. Half of the tumors with Hras1 mutations have loss of heterozygosity (LOH) at Hras1. In the study reported here, seven tumors with LOH at Hras1, six heterozygous for Hras1, and six without Hras1 mutations were analyzed to define the extent of LOH on chromosome (Chr) 7. Microsatellite polymorphisms present in CBA/J mice were used as informative allelic markers. Tumors with LOH at Hras1 showed consistent allelic loss at the distal portion of Chr 7. The boundary of allelic loss lay between the tyrosinase and hemoglobin beta chain loci, which are 6 cM apart. None of the tumors that remained heterozygous for Hras1 or had no Hras1 mutations had evidence of chromosomal loss involving Chr 7. Because LOH was only detected in advanced lesions long after exposure to 4NQO had ceased, we presume that the chromosomal alterations by which LOH occurred were independent of the carcinogen exposure. The development of LOH in only half of the tumors with Hras1 point mutations suggests that LOH was not caused by the initial Hras1 point mutation but was a highly selected event during tumorigenesis.
Mol Carcinog 1997 May
PMID:Consistent allelic loss on mouse chromosome 7 distal to tyrosinase in 4-nitroquinoline-1-oxide-induced oral cavity tumors with loss of heterozygosity at Ha-ras-1. 918 Sep 23

The aim of this study was to demonstrate that modification of the cellular redox-equilibrium occurs as a consequence of antioxidant nutrients intake (carotenoids, vitamine E and vitamine C) and that these nutrients play a role in the pigmentation of the skin without any UV exposure. We conducted a randomized, double-blind study in 20 healthy subjects to evaluate and to compare the efficacy of two mixtures of dietary antioxidants with regard to direct determination of melanin and carotenes by chromametry at selected skin sites and multiple reflection spectrometry from a 1 cm2 region of skin of different parts of the body. Efficacy was assessed by a significant improvement of these parameters, in comparison with measurements performed on the day of randomization, before dietary supplement intake. The formulations per capsule of study dietary supplements are: 13 mg of beta-carotene, 2 mg of lycopene, 5 mg of vitamine E and 30 mg of vitamine C (B13/L2) or 3 mg of beta-carotene, 3 mg of lycopene, 5 mg of vitamine E and 30 mg of vitamine C (B3/L3). A 8-week B13/L2-supplementation lead to a detectable carotenodermia whereas the B3/L3-supplementation not. Signicative increase of melanin concentrations in skin were found after 4, 5, 6 and 8 weeks of dietary antioxidant intake in both groups (p < 0.05). These results are discussed with regard to the redox control theory of melanocytes which regulates the tyrosinase activity.
Biochem Mol Biol Int 1997 Aug
PMID:Evidence for antioxidant nutrients-induced pigmentation in skin: results of a clinical trial. 928 71

The TP-ras transgenic mouse line expresses an activated human T24 Ha-ras gene with a mutation in codon 12, regulated by a mouse tyrosinase promoter. The transgene is expressed in melanocytes of the skin, eyes, and brain. The mice develop cutaneous melanoma when treated with 7,12-dimethylbenz[a]anthracene. Cell lines have been generated from the cutaneous tumors and metastatic lesions. By using fluorescence in situ hybridization with mouse whole chromosome paints, the cell lines were characterized for chromosomal abnormalities. Key findings in the tumor cells included translocations of chromosome 4 and alterations in chromosome 6. One tumor cell line contained a double translocation involving chromosomes 3 and 6. To extend the results of the chromosome 4 painting, Southern analysis of the p15INK4B, p16INK4A, and p19INK4D genes was performed. Our data indicated that there were homozygous and partial allelic deletions and polymorphisms in the region of chromosome 4 containing these genes, resulting in the absence or reduced expression of the p16 product. These findings are similar to those reported for human melanoma, and the TP-ras transgenic mouse may therefore be a valuable model for studying novel strategies for melanoma prevention and treatment.
Mol Carcinog 1997 Sep
PMID:Chromosomal and genetic alterations of 7,12-dimethylbenz[a]anthracene-induced melanoma from TP-ras transgenic mice. 932 38

During the pachytene stage of meiotic prophase in male mammals, the X and Y chromosomes become transcriptionally inactive and establish a chromatin domain, the sex body, that is visually distinct from the transcriptionally active autosomes. We used objective criteria to assess these chromatin differences by DNase I sensitivity (DS) of sex chromosome and autosomal sequences at both the cytological and molecular levels. For cytological studies, in situ nick translation techniques were used on air-dried preparations of testicular cells. For molecular studies, nuclei from pachytene spermatocytes were subjected to nuclease sensitivity assays. Both sex-linked and autosomal sequences were assessed, including some gene sequences that are expressed and some that are not expressed in pachytene spermatocytes. There was a wide range of DS in different genomic sequences; however, the sex-linked sequences generally were less nuclease sensitive than were autosomal sequences. Interestingly, a hot spot of recombination (within the Eb gene) showed a high level of nuclease sensitivity, while a cold spot of recombination (centromeric satellite region) exhibited lower sensitivity, more similar to that of sex-linked sequences. We also examined the nuclease sensitivity of a tyrosinase transgene insert, TyBS. In one line of mice, the transgene insert is X-linked, whereas in another, it is autosomal. The transgene was less nuclease sensitive when X-linked than as an autosomal insert. These results support the hypothesis that in pachytene spermatocytes the XY chromosome pair is more condensed and inaccessible to enzymatic digest, whereas the autosomal chromatin is in a more open configuration. In addition, we examined the nuclease sensitivity of some of the same genes in the earlier leptotene/zygotene prophase stage, when the sex chromatin is not maximally condensed. We found that while autosomal gene nuclease sensitivity was equivalent to that at the pachytene stage, X-linked sequences were more nuclease sensitive. Overall, these differences in chromatin nuclease sensitivity correlate with differences in meiotic recombination activity and may be mechanistically related.
Mol Reprod Dev 1998 Jan
PMID:Chromatin configuration during meiosis I prophase of spermatogenesis. 940 97


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