Biomedical subjects
Publications and source records attributed to G Agrup.
Urinary excretion of 5-S-cysteinyldopa was investigated in 12 genetically dark-skinned men living in Sweden. Ten subjects showed excretion values in the same range as persons of Swedish origin, whereas the excretion was higher in 2 subjects.
The hypothesis that only melanosomal catecholic amino acids contribute to melanin formation was tested by studying adult bovine eyes in which pigment synthesis is considered to be low or absent. Dopa and 5-S-cysteinyldopa were investigated in different cell fractions of the choroid and retinal pigment epithelium of cattle. Most of the dopa and 5-S-cysteinyldopa was found in the cytoplasm and very little in the large granule fraction. The presence of cysteinyldopa in the adult eye is evidence of tyrosinase activity, but the catechol amino acids in the cytoplasm probably do not give rise to melanin formation. It is assumed that they instead are excreted from the cells.
Determinations of the urinary excretion of 5-S-cysteinyldopa were performed in 571 patients previously treated by surgery for melanoma or melanoma metastasis. 90% of the 161 patients with metastases showed values exceeding 0.15 mg/24 h, and 9% of the 410 patients without metastases had such values. The increase in 5-S-cysteinyldopa excretion was generally more pronounced in men with metastases than in women, 98% of the men and 77% of the women with metastases showing values exceeding 0.15 mg/24 h. High levels of 5-S-cysteinyldopa are of grave prognostic significan4% died within one month, and only 3% survived for more than a year. In Sweden, determination of 5-S-cysteinyldopa in patients operated on for melanoma gives maximum information in the winter (October--March), when sun exposure does not influence the excretion levels.
ESR spectra of synthetic melanins formed from dopa and from 5-S-cysteinyldopa and of melanins isolated from human melanomas were studied. Alkali-soluble melanin synthesized from cysteinyldopa showed a signal similar to that of insoluble melanin synthesized from dopa, but also a simple fine structure. Trichochromes C and F synthesized from 5-S-cysteinyldopa had a broader signal than dopamelanin, and in addition a hyperfine structure that could be explained by the presence of manganous ions. An insoluble eumelanin from a human melanoma with a sulphur content of 5% showed an ESR spectrum consisting of one line like dopamelanin. An alkali-soluble phaeomelanin from a human melanoma with a sulphur content of 10% showed a very broad signal with a hyperfine structure that could be explained by the presence of manganous ions.
A previous finding of pronounced excretion of trichochromes in a patient with metastasizing melanoma and diffuse melanosis prompted this study on trichochromes in another patient with these two features. The patient now reported also excreted large amounts of trichochromes. Iit is suggested that diffuse melanosis in metastatic melanoma patients is due to deposition of trichochromes in the tissue.
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A method is described for quantitative determination of 5-S-cysteinyldopa and Dopa in serum involving high-pressure liquid chromatographic analysis (HPLC) and electrochemical detection. The chromatographic system allows estimation of injected amounts corresponding to 25 pg of 5-S-cysteinyldopa and Dopa. In normal subjects the mean serum 5-S-cysteinyldopa concentration was 2.8 ng/ml (range 0.4--12 ng/ml) and the mean serum Dopa 6.3 ng/ml (range 4--10 ng/ml). Patients with melanoma metastases showed increased serum concentrations of 5-S-cysteinyldopa.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
The urine of patients with melanoma metastases and increased urinary excretion of 5-S-cysteinyldopa was examined for trichochromes. Five of 16 patients showed urinary excretion of trichochromes B and C. None excreted trichochromes E or F. All patients showing trichochrome excretion had very large amounts of cysteinyldopa in their urine.
The excretion of the specific melanocytic metabolite 5-S-cysteinyldopa was studied in patients with psoriasis treated by 8-methoxypsoralen and UVA light. A pronounced increase was found after only 2 days treatment, although no increase in pigmentation could yet be observed. Peak values for urinary 5-S-cysteinyldopa were noted after 1 or 2 weeks treatment. Increase in pigmentation persisted after the excretion maxima for 5-S-cysteinyldopa.
Red cock feathers (Rhode Island) were found to contain dopa and cysteinyldopa, trichochromes B and C, and two unidentified trichochromes. Trichochromes E and F were not found. Previous findings of trichochromes E and F may be explained as artifacts.
Free dopa and 5-S-cysteinyldopa were extracted from two human melanomas. Subsequent hydrolysis of carefully washed melanoma tissue released dopa and 5-S-cysteinyldopa, indication the presence of these catechol amino acids in proteins. Cysteinyldopa-containing proteins may represent the antigens previously demonstrated in human melanomas.
The presence of trichochromes B and C in red human hair was confirmed with an analytical procedure which does not give rise to the formation of these compounds as artifacts. The trichochrome precursor 5-S-cysteinyldopa previously demonstrated in red guinea-pig hair was not detected in red human hair.
Decarboxytrichochromes B and C were isolated from a melanoma metastasis in a red-haired man, indicating the presence of trichochromes B and C in the tissue. Trichochromes E and F were not detected.
The usefulness of the formaldehyde (FA) and glyoxylic acid (GA) methods for the fluorescence histochemical demonstration of dopa thioethers has been tested using protein droplet models. Similar fluorescence intensities were recorded from these compounds after either FA or GA treatment. Cysteinyldopa gave a high fluorescence yield similar to that obtained from dopamine and dopa in the FA reaction, whereas gluatitodopa showed a lower, although clearly visible fluorescence. Since the FA method seemed to be the most useful one for demonstration of catechol thioethers, the FA-induced fluorophores of these compounds were further characterized by microspectrofluorometry. The spectral characteristics of the thioether fluorophores (excitation maxima at 420 nm and emission maxima at 480-485 nm) distinguish these substances from dopa and other compounds fluorogenic in the Falck-Hillarp method. Dopa thioethers are proposed to form fluorophores with FA in a manner analogous to that of the primary catecholamines i.e. via low-fluorescent tetrahydroisoquinolines, along two different pathways, to strongly fluorescent 3,4-dihydroisoquinolines and 2-methyl-dihydroisoquinolinium compounds. These dihydroisoquinolines are in a pH-dependent tautomeric equilbrium with their quinoidal forms as reflected by a characteristic spectral shift upon acidification. The results of this study provide the guide-lines for the characterization of fluorogenic compounds in pigment-forming cells.
5-S-cysteinyldopa is metabolized by O-methylation on incubation with a liver extract and S-adenosyl methionine. O-methylated 5-S-cysteinyldopa isolated from melanoma urines by ion exchange and paper chromatography was identified by gas chromatography-mass spectrometry and NMR.