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Biomedical subjects

H Rorsman

Publications and source records attributed to H Rorsman.

At least 73 records · Page 4Linked to original sources

5-OH-dopa, product of and substrate for tyrosinase.

The formation of 5-OH-dopa on incubation of tyrosine or dopa with mushroom tyrosinase was studied. Dopa oxidase activity was defined by measuring the formation of 5-S- and 2-S-cysteinyldopa from dopa in the presence of excess amounts of cysteine. This procedure quantitating the immediate nucleophilic reaction products of dopaquinone constitutes a new method for assessing tyrosinase activity. The rate of 5-OH-dopa formation from dopa was similar to that of the formation of dopa from tyrosine. The rate of dopaquinone formation was one order of magnitude higher. When tyrosine was oxidized in the presence of ascorbic acid, 5-OH-dopa formation represented 14% of the original amount of tyrosine. At low concentration of dopa, formation of 5-OH-dopa was proportional to the dopa concentration. At high concentrations the relative quantity of 5-OH-dopa formed decreased. Tyrosine in high concentrations inhibited the formation of 5-OH-dopa from dopa. 5-OH-dopa proved to be a substrate for tyrosinase. The rate of oxidation of 5-OH-dopa was similar to that of dopa. The oxidation products of 5-OH-dopa were transformed into relatively stable fluorophores.

Basidiomycota↗

5-S-Cysteinyldopa in ganglion stellatum.

5-S-Cysteinyldopa, an amino acid formed by nucleophilic addition of cysteine to dopaquinone, has been detected in the ganglion stellatum of the cow in amounts varying between 21 and 35 ng/g ganglionic tissue. Dopa was present in slightly higher quantities. Cysteinyldopa has previously been regarded as a substance unique for the melanocytes, where it forms melanin after oxidation and polymerization. At present only hypothetical explanations of our finding can be offered. The content of 5-S-cysteinyldopa in ganglion stellatum may be the result of dopa oxidation in ganglionic cells. An uptake mechanism for circulating cysteinyldopa may exist. Localization of cysteinyldopa to aberrant melanocytes or to aged SIF-cells in the ganglia should also be borne in mind.

3,4-Dihydroxyphenylacetic Acid↗

DOPA in sympathetic nerve tissue--a possible source of serum DOPA in albino animals.

Dopa, catecholamines, and dopac were determined in superior cervical ganglia of albino rats. The average amount of dopa in ganglia of control animals was 1.1--1.6 micrograms/g. The concentrations of catecholamines and dopac were similar to values reported by others. The tyrosine hydroxylase inhibitor alpha-methylparatyrosine methyl ester caused marked decrease in the dopa concentration in the ganglia. The effect of reserpine was less pronounced. The aromatic amino acid decarboxylase inhibitor NSD 1015 markedly increased the dopa concentration.

3,4-Dihydroxyphenylacetic Acid↗

5-S-Cysteinyldopa and dopa in serum during treatment with 8-methoxypsoralen and UVA light.

5-S-Cysteinyldopa and dopa concentrations in serum were studied by high-performance liquid chromatography (HPLC) in patients with psoriasis treated by 8-methoxypsoralen and UVA light. A marked increase in 5-S-Cysteinyldopa was found after 3 days' treatment, although no increase in pigmentation could yet be observed. The highest concentrations of 5-S-Cysteinyldopa in serum were noted after 1 or 2 weeks' treatment. In one patient who showed no increase in serum 5-S-Cysteinyldopa treatment was unsuccessful. During PUVA treatment of 3 patients with psoriasis confined to the palms and/or soles a delayed increase in serum 5-S-Cysteinyldopa was noted after 5 weeks. This delayed response after treatment of a small area of the body is remarkable, and may indicate the formation of a systemic melanocyte stimulation factor. There was no increase in the serum dopa concentrations during PUVA treatment, and dopa analysis was of no value in assessing the activity of the melanocytes. Some unexpectedly high dopa values recorded before and during PUVA treatment may be explained by the fact that dopa originates in the nervous system or the adrenals.

Adult↗

Treatment of malignant melanoma with dacarbazin (DTIC-DOME) with special reference to urinary excretion of 5-S-cysteinyldopa.

Seventeen patients were given DTIC, 200 mg/m2/day in five-day courses every four to six weeks. In four patients (stage II) treated on an adjuvant basis, tumor recurrence has been verified in three. Four of the palliatively treated patients were also given DTIC by regional intra-arterial infusion with minimal positive tumor effect and minimal toxicity. 5-S-cysteinyldopa excretion in urine was checked continuously in all patients. Tumor recurrence was revealed in two patients given DTIC on an adjuvant basis three and four months before clinical signs of tumor. In the palliatively treated patients, 5-S-cysteinyldopa excretion increased in 5/6 patients judged to have stable disease, before tumor progression was clinically detectable. The use of 5-S-cysteinyldopa examination is a valuable adjunct to the follow-up of the effect of DTIC therapy in melanoma patients.

Adult↗

Ranking of glucocorticoid creams and ointments.

20 corticosteroids ointments and 19 corticosteroid creams available on the Swedish market in January 1977 were tested for their blanching effect. Three ointments and three creams showing pronounced blanching were tested only without occlusion. Hydrocortisone preparations were tested only with occlusion. Other preparations were tested with and without occlusion. All ointments and creams were tested at four randomized sites on the flexor aspect of the forearm in each of 11 or 12 subjects. When used occlusion was applied for 6 hours. Repeated readings were made, using scores 0, 1, 2, and 3. The reading at the time when most preparations showed blanching were analysed statistically. The scores for blanching showed a Poisson distribution when the mean score was less than or equal to 1. Classification of preparations according to blanching was facilitated by the fact that statistical methods for Poisson distribution could be used. A ranking of corticosteroids based on vasoconstriction was obtained, and four different groups for ointments and four for creams emerged. The arbitrary nature of any ranking and grouping of steroids is evident from the data presented.

Administration, Topical↗

5-S-cysteinyldopa, dopa, and dopamine in the kidney and some other tissues.

5-S-Cysteinyldopa, dopa, and dopamine levels were determined by HPLC and electrochemical detection in serum, urine, kidney, spleen, heart, and sympathetic ganglion of guinea-pig. The kidney showed high levels of 5-S-cysteinyldopa, but also of dopa and dopamine, thus demonstrating the role of the renal ti-sue in the excretion of these substances. The concentrations found in spleen and heart may indicate specific catechol-containing structures in these organs.

Animals↗

Dopa and 5-S-cysteinyldopa in the serum of albino, black, and red guinea pigs.

Dopa and 5-S-cysteinyldopa levels in serum of albino, red, and black guinea-pigs were quantified. The levels of both amino acids were lower in the albino than in the pigmented animals. It is suggested that the serum levels of dopa and 5-S-cysteinyldopa in pigmented animals reflect tyrosine and dopa oxidation activity in the melanocytes.

Animals↗

5-S-cysteinyldopa as a substrate for tyrosinase.

Oxidation of 5-S-cysteinyldopa by mushroom tyrosinase was studied by measuring 5-S-cysteinyldopa consumption with HPLC. 5-S-cysteinyldopa was found to be a substrate for tyrosinase, but our results suggests that a self-catalysed oxidation induced by enzymatically formed 5-S-cysteinyl dopaquinone also takes place. Dopa oxidation by tyrosinase was determined by measuring substrate consumption with HPLC. The oxidation of 5-S-cysteinyldopa was markedly accelerated in the presence of dopa. This could be explained by dopaquinone oxidation of 5-S-cysteinyldopa, which has a lower oxidation potential than dopa.

Catechol Oxidase↗

5-hydroxydopa, a new compound in the Raper-Mason scheme of melanogenesis.

Oxidation of tyrosine or dopa by tyrosinase leads to the formation of 5-OH-dopa, a compound previously unknown in melanogenesis. 5-OH-dopa, first detected as an unknown compound on HPLC of the dopa-tyrosinase incubate, was purified by Al2O3-adsorption, semipreparative HPLC, and ion-exchange chromatography. 5-OH-dopa was identified by comparison with the authentic compound in several chromatographic systems, by electrochemical oxidation studies and by mass spectrometry.

Chemical Phenomena↗

Melanogenesis in cultured human neuroblastomas.

The catecholic amino acids, dopa and 5-S-cysteinyldopa, and the dopamine metabolite, homovanillic acid, were determined in 8 neuroblastomas. 5-S-Cysteinyldopa and/or dopa were detected in all cases and homovanillic acid was present in 5. Dopa was also found in two tumours in which no definite histological diagnosis could be made. Neuroblastoma cells were cultured from 7 patients. The ageing of human sympathoblasts in culture was accompanied by modifications in the ability to synthetize dopa, which is a precursor of catecholamines as well as of melanins, and the metabolite homovanillic acid. An increase in the levels of 5-S-cysteinyldopa, a metabolite of the melanocytes, has been observed. Concurrent modifications of ultrastructural morphology with the disappearance of granular vesicles and appearance of melanosomes were noticed. This modulation of the original phenotypic expression commonly resulted in cell death, but in one case of metastatic adenopathy of a neuroblastoma we have been able to establish a permanent pigmented cell line.

Animals↗

Analysis of cysteinyldopas, dopa, dopamine, noradrenaline and adrenaline in serum and urine using high-performance liquid chromatography and electrochemical detection.

The catecholic amino acids, dopa, 2-S- and 5-S-cysteinyldopa, and 2,5-S,S-dicysteinyldopa were determined qualitatively in serum from patients with malignant melanoma by reversed-phase high-performance liquid chromatography, using electrochemical detection. In urine the catecholamines dopamine, noradrenaline and adrenaline were also determined qualitatively, as well as the above-mentioned compounds, in a single chromatographic run. The conditions were optimized by changing the pH of the mobile phase and by the addition of methanesulphonic acid. A comparison was made between the performance of four commercial reversed-phase packing materials containing chemically bonded octadecyl groups, using a standard mixture of catecholic amino acids. The influence of ionic strength, pH and amount of methanesulphonic acid on retention was investigated.

Adsorption↗

Intracellular distribution of dopa and 5-S-cysteinyldopa in pigment cells with minimal pigment formation.

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.

Animals↗

5 years' experience of 5-S-cysteinyldopa in melanoma diagnosis.

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.

Adult↗