Thermoelectric signature of quantum critical phase in a doped spin-liquid candidate.

Quantum spin liquid is a nontrivial magnetic state of longstanding interest, in which spins are strongly correlated and entangled but do not order; further intriguing is its doped version, which possibly hosts strange metal and unconventional superconductivity. A promising candidate of the doped spin liquid is a triangular-lattice organic conductor, κ-(BEDT-TTF)4Hg2.89Br8, recently found to hold metallicity, spin-liquid-like magnetism, and BEC-like superconductivity. The nature of the metallic state with the spin-liquid behaviour is awaiting to be further clarified. Here, we report the thermoelectric signature that mobile holes in the spin liquid background are in a quantum critical state and it pertains to the BEC-like superconductivity. The Seebeck coefficient divided by temperature, S/T, is enhanced on cooling with logarithmic divergence indicative of quantum criticality. Furthermore, the logarithmic enhancement is correlated with the superconducting transition temperature under pressure variation, and the temperature and magnetic field profile of S/T upon the superconducting transition change with pressure in a consistent way with the previously suggested BEC-BCS crossover. The present results reveal that the quantum criticality in a doped spin liquid emerges in a phase, not at a point, and is involved in the unconventional BEC-like nature.

Identification of Shell Colour Pigments in Marine Snails Clanculus pharaonius and C. margaritarius (Trochoidea; Gastropoda).

Colour and pattern are key traits with important roles in camouflage, warning and attraction. Ideally, in order to begin to understand the evolution and ecology of colour in nature, it is important to identify and, where possible, fully characterise pigments using biochemical methods. The phylum Mollusca includes some of the most beautiful exemplars of biological pigmentation, with the vivid colours of sea shells particularly prized by collectors and scientists alike. Biochemical studies of molluscan shell colour were fairly common in the last century, but few of these studies have been confirmed using modern methods and very few shell pigments have been fully characterised. Here, we use modern chemical and multi-modal spectroscopic techniques to identify two porphyrin pigments and eumelanin in the shell of marine snails Clanculus pharaonius and C margaritarius. The same porphyrins were also identified in coloured foot tissue of both species. We use high performance liquid chromatography (HPLC) to show definitively that these porphyrins are uroporphyrin I and uroporphyrin III. Evidence from confocal microscopy analyses shows that the distribution of porphyrin pigments corresponds to the striking pink-red of C. pharaonius shells, as well as pink-red dots and lines on the early whorls of C. margaritarius and yellow-brown colour of later whorls. Additional HPLC results suggest that eumelanin is likely responsible for black spots. We refer to the two differently coloured porphyrin pigments as trochopuniceus (pink-red) and trochoxouthos (yellow-brown) in order to distinguish between them. Trochopuniceus and trochoxouthos were not found in the shell of a third species of the same superfamily, Calliostoma zizyphinum, despite its superficially similar colouration, suggesting that this species has different shell pigments. These findings have important implications for the study of colour and pattern in molluscs specifically, but in other taxa more generally, since this study shows that homology of visible colour cannot be assumed without identification of pigments.

Heterospecific female mimicry in Ficedula flycatchers.

Mimicry is a widespread phenomenon. Vertebrate visual mimicry often operates in an intraspecific sexual context, with some males resembling conspecific females. Pied flycatcher (Ficedula hypoleuca) dorsal plumage varies from the ancestral black to female-like brown. Experimental studies have shown that conspecific and heterospecific (collared flycatcher, F. albicollis) individuals of both sexes respond, at least initially, to brown individuals as if they were female. We quantified the perceptual and biochemical differences between brown feathers and found that brown pied flycatcher males are indistinguishable from heterospecific, but not from conspecific, females in both aspects. To our knowledge, this is the first evidence of a visual mimetic signalling system in a sexual context where the model is heterospecific to the mimic. By only mimicking heterospecific females, brown pied flycatcher males can establish territories next to the more dominant collared flycatcher in sympatry, suffer less aggression by darker conspecifics in allopatry and preserve within-species sexual recognition throughout the breeding range. A closer look at the evolutionary history and ecology of these two species illustrates how such a mimetic system can evolve. Although likely rare, this phenomenon might not be unique to Ficedula flycatchers.

Age-dependent changes in eumelanin composition in hairs of various ethnic origins.

Hair pigmentation is one of the most conspicuous phenotypes of humans. From a chemical point of view, however, data remain scarce regarding human hair pigmentation characteristics. To determine melanin content and composition in human eumelanic hair from individuals of different ethnic origins and at different ages, we collected hair from 56 subjects with eumelanic hair from each group of African-American, East Asian, and Caucasian origin. The 56 subjects consist of 14, seven each of males and females, each from four age classes of younger than 11, between 12 and 19, between 20 and 45, and older than 46. We analysed hair colour scale, total melanin value, and contents of pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA). We measured age-dependent increases in the relative quantity of eumelanin in pigmented human hairs in the three ethnic groups. Regarding melanin composition, we observed an increase in the PDCA/PTCA ratio with age in African-American and Caucasian hairs until approaching the quite constant level of the ratio in East Asian hairs in the elderly individuals. Our results evidence differences in the content and composition of eumelanin in human hair among African-American, Caucasian and East Asian individuals. Furthermore, we show evidence of age-dependent changes in the quantity and quality of eumelanin in pigmented human hairs. In particular, the age-dependent modification of the PDCA/PTCA ratio, a marker for 5,6-dihydroxyindole units in eumelanin, suggests a chronological evolution of hair follicle melanocyte phenotype (e.g. decrease in dopachrome tautomerase expression).

Diversity of human hair pigmentation as studied by chemical analysis of eumelanin and pheomelanin.

Hair colour is one of the most conspicuous phenotypes in humans, ranging from black, brown, blond to red. This diversity arises mostly from the quantity and ratio of the black-dark brown eumelanin and the reddish-brown pheomelanin. To study the chemical basis underlying the diversity of hair colour, we have developed several chemical methods to quantify those two pigments. Alkaline H(2) O(2) oxidation affords pyrrole-2,3,5-tricarboxylic acid (PTCA) as a eumelanin marker and thiazole-2,4,5-tricarboxylic acid (TTCA) as a pheomelanin marker. Pheomelanin can also be analysed as 4-amino-3-hydroxyphenylalanine (4-AHP) after hydroiodic acid hydrolysis. Using those methods, we evaluated the contents of eumelanin and pheomelanin (the 'chemical' phenotype) in human hairs of black, dark brown, brown, light brown, blond and red colour (the 'visual' phenotype). Eumelanin contents decrease in that order, with a trace but constant level of pheomelanin, except for red hair which contains about equal levels of pheomelanin and eumelanin. Thus, the chemical phenotype correlates well with the visual phenotype. The genotype of melanocortin-1 receptor (MC1R), a gene regulating the red hair phenotype, is predictive of hair melanin expressed as the log value of eumelanin to pheomelanin ratio, with a dosage effect evident. Hair melanin contents were also analysed in patients with various hypopigmentary disorders including Hermansky-Pudlak syndrome, Menkes disease, proopiomelanocortin deficiency, cystinosis, malnutrition and trace metal deficiency. The chemical phenotype helped evaluate the precise effects of each disease on pigmentation. In studies of human hair, the chemical phenotype will find more and more application as an objective measure of pigmentation.

Lymphangiogenesis associated with acute cellular rejection in rat liver transplantation.

Lymphangiogenesis may be important for the cellular immune response in liver transplantation. In the present study, we examined lymphangiogenesis in liver allografts displaying acute cellular rejection (ACR), or long-term acceptance, or severe ACR plus antibody-mediated rejection (AMR). ACR and subsequent long-term graft acceptance developed in liver transplantations from DA to PVG rats without immunosuppression (mean survival time more than 90 days). Severe ACR and AMR developed in liver transplantations from DA to Lewis rats without immunosuppression (mean survival = 11 days). Normal DA donor livers before transplantation showed a small number of lymphatic vessels around portal veins. DA liver grafts in PVG showed ACR with lymphangiogenesis in portal areas and portal-portal bridging areas with cellular infiltration. Newly formed lymphatic vessels in ACR were characterized by proliferating endothelial cells with expression of the homeobox transcription factor PROX-1 and surrounded by discontinuous basement membranes. Thereafter, the infiltrates spontaneously disappeared, and the grafts survived more than 90 days. During the resolution of the cellular infiltration, expanded lymphatic vessels were packed with many lymphocytes. Thereafter, the number of lymphatic vessels decreased. In contrast, severe ACR and AMR in DA-to-Lewis transplantations showed lymphatic vessels disappeared with edema in the portal areas at day 11. In conclusion, lymphangiogenesis occurred during ACR. It may be involved in the resolution of ACR and reduction of inflammation. In severe ACR and AMR, lymphatic vessels were destroyed, which may be involved in persistent severe inflammation.

Serum 5-S-cysteinyldopa levels in patients with psoriasis undergoing narrowband ultraviolet B phototherapy.

BACKGROUND: Ultraviolet (UV) B radiation from sunlight can result in tanning or burning of the skin. Narrowband UVB (NB-UVB), a relatively new light source that is not yet widely available, is effective for treating generalized psoriasis without the use of psoralens. AIMS: The melanin-related metabolite 5-S-cysteinyldopa (5-S-CD), which reflects pheomelanin production, has been used as a biological marker of melanoma progression, but there are no studies available on therapeutic UVB effects on serum 5-S-CD of human subjects. In the present study, we measured the time course of changes in serum levels of 5-S-CD in patients with psoriasis undergoing NB-UVB phototherapy. METHODS: In total, 11 Japanese patients with generalized psoriasis vulgaris received NB-UVB treatment five times per week, at an initial dose of 0.1 J/cm(2). The dose was increased by 10-20% per treatment for > 20 treatments. Serum samples were taken before and 3, 7, 10, 14 and 28 days after phototherapy. RESULTS: After 4 weeks of NB-UVB treatment, 9 of 11 patients were in remission, confirming the effectiveness of NB-UVB for treating Japanese patients with psoriasis. Two patients withdrew before day 28 because of other complications. Mean level of 5-S-CD in serum was significantly increased on day 7, 10 14 and 28 compared with the level before phototherapy and it peaked on day 10. CONCLUSIONS: Serum 5-S-CD levels were significantly increased by therapeutic UVB exposure. Sustained levels of 5-S-CD in serum appear to reflect the degree of skin injury during NB-UVB phototherapy.

TRP-2 expression protects HEK cells from dopamine- and hydroquinone-induced toxicity.

We previously reported that melanogenic enzyme TRP-2 (or DCT for DOPAchrome tautomerase) expression in WM35 melanoma cells resulted in increased intracellular GSH levels, reduction in DNA damage induced by free radicals, and decreased cell sensitivity to oxidative stress. These effects seemed to depend on a particular cellular context, because none of them were found to occur in HEK epithelial cells. We postulated that the TRP-2 beneficial effect observed in WM35 cells in the oxidative stress situation may relate to quinone metabolization and, more precisely, to the ability of TRP-2 to clear off related toxic metabolites, resulting in a global redox status modification. Here, a comparative protein expression profiling of catecholamine biosynthesis enzymes and detoxification enzymes was conducted in WM35 melanoma cells and in HEK epithelial cells, in comparison with normal human melanocytes. Results showed that WM35 cells, but not HEK cells, expressed enzymes involved in catecholamine biosynthesis, suggesting that their quinone-related toxic metabolites were present in WM35 cells but not in HEK cells. To address the issue of a possible TRP-2 beneficial effect toward quinone toxicity, cell survival experiments were then conducted in HEK cells using dopamine and hydroquinone at toxic concentrations. We showed that TRP-2 expression significantly reduced HEK cell sensitivity to both compounds. This beneficial property of TRP-2 was likely to depend on the integrity of its DOPAchrome tautomerase catalytic site, because both TRP-2(R194Q) and TRP-2(H189G), which have lost their DOPAchrome tautomerase activity, failed to modify the HEK cell response to dopamine and hydroquinone. These results suggest that TRP-2 acts on quinone metabolites other than DOPAchrome, e.g., in the catecholamine pathway, and limits their deleterious effects.

The melanogenic system of the liver pigmented macrophages of Rana esculenta L.--tyrosinase activity.

The enzyme system responsible for Amphibian Kupffer Cell (KC) melanogenesis has not been entirely elucidated. This research demonstrates that the KC melanosomes of Rana esculenta L. possess a tyrosine-hydroxylase (TH) activity, showing that a tyrosinase is the enzyme involved in the melanogenesis. The TH reaction depends on catalytic Dopa as a cofactor and is not affected by catalase or H2O2, showing that it is catalysed by the tyrosinase and not by the peroxidase present in the melanosomes. The TH reaction is activated by Cu2+ ions but not by other tyrosinase activators such as limited proteolysis, protein ageing, and Sodium Dodecyl Sulphate (SDS). SDS inhibited the KC TH activity even below the critical micelle concentration. All these results suggest that the KC-tyrosinase differs in structure from other known tyrosinases. Using anti-KC-tyrosinase antobodies, we observed that the sites of the tyrosinase location within the cell are the same as those described in the melanocytes. In the immunoblots, the anti-KC-tyrosinase antibodies also recognised two protein bands, at the higher molecular weight ranges, in the protein electrophoretic pattern. Moreover, the tyrosinase activity was limited to the highest molecular weight band of about 260 kDa, suggesting that the enzyme activity could depend on a molecular aggregate. The melanin produced in the liver was found to be a 5,6-dihydroxyindole-rich eumelanin similar to the Sepia melanin.

Intrathecal administration of ATP produces long-lasting allodynia in rats: differential mechanisms in the phase of the induction and maintenance.

Several lines of evidence suggest that extracellular ATP plays a role in pain signaling through the activation of ionotropic P2X-receptors, especially homomeric P2X3- and heteromeric P2X2/3-receptors on capsaicin-sensitive and -insensitive primary afferent neurons, respectively, at peripheral and spinal sites. We investigated the mechanisms of the induction and maintenance of mechanical allodynia produced by a single intrathecal (i.t.) administration of ATP in rats. We found that i.t. administration of ATP and the P2X-receptor agonist alpha,beta-methylene-ATP produced tactile allodynia which lasted more than 1 week. The i.t. ATP- and alpha,beta-methylene-ATP-produced long-lasting allodynia remained in neonatal capsaicin-treated adult rats. I.t. administration of a P2X3/P2X2/3-receptor selective antagonist completely prevented the induction (co-administration on day 0) and partially attenuated the early phase (day 1 post-ATP administration), but not the late phase (day 7 post-ATP administration) of maintenance of allodynia. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 completely prevented the induction phase, but not the early and late phases of maintenance of allodynia. Immunohistochemical and immunoblotting studies for microglial and astrocytic markers revealed that i.t. ATP administration caused spinal microglial activation within 1 day, and astrocytic activation which peaked at 1-3 days after ATP administration. Furthermore, minocycline, a microglial inhibitor, attenuated the induction but not the early and late phases of maintenance, while fluorocitrate, a glial metabolic inhibitor, attenuated the induction and the early phase but not the late phase of maintenance. Taken together, these results suggest that the activation of P2X-receptors, most likely spinal P2X2/3-receptors on capsaicin-insensitive primary afferent neurons, triggers the induction of long-lasting allodynia through NMDA receptors, and the induction and early maintenance phase, but not the late phase, is mediated through the functions of spinal glial cells.

Reduplicated basal lamina of the peritubular capillaries in renal biopsy specimens.

Reduplicated basal lamina of the peritubular capillaries (PTC) is usually found in kidney allografts in association with chronic transplant nephropathy and sometimes in native renal biopsies. In order to assess the incidence of this phenomenon in native renal biopsy specimens, we have carried out a retrospective review of the diagnostic ultrastructural pathology records of 80 consecutive renal biopsies excluding renal allografts and children with clinical signs of heavy proteinuria. Reduplicated basal lamina of the PTC was found in 19 out of the 80 cases (23.8%) with renal diseases. It was frequently seen in lupus nephritis, IgA nephropathy, and membranoproliferative glomerulonephropathy, being the subtypes of mesangial proliferative lesions. In a few cases it was also found in anti-neutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis and benign nephrosclerosis renal biopsies. Reduplicated basal lamina of the PTC was strongly associated with glomerular and peritubular inflammation, and tubular necrosis. Peritubular interstitial edema, slight to moderately increased collagen fibrils, many spiraled collagen fibrils (indicative of degeneration), and collagen fibrils drawing from basal lamina were found around the reduplicated basal lamina of the PTC but not in normal basal lamina. These results indicate that in native renal biopsy specimens, reduplication of the basal lamina of the PTC is associated with endothelial cell injury and capillary permeability abnormality.

A new antigen retrieval method using citraconic anhydride for immunoelectron microscopy: localization of surfactant pro-protein C (proSP-C) in the type II alveolar epithelial cells.

In the attempt to develop a pre-embedding immunoelectron microscopic method with improved ultrastructral morphology, we examined an antigen retrieval (AR) method using citraconic anhydride, and compared the effects of glutaraldehyde fixation with routine paraformaldehyde fixation in the pre-embedding immunoelectron microscopic method with reference to the localization of surfactant-associated pro-protein C (proSP-C) in the lung. The glutaraldehyde-fixed tissues were immunostained after AR in 0.05% citraconic anhydride solution, pH 7.4, at 98 degrees C for 60 min. In routine pre-embedding immunoelectron microscopic method using paraformaldehyde fixation, proSP-C positive products were distributed sporadically in the type II alveolar epithelial cells. In glutaraldehyde-fixed tissues without the AR method, proSP-C products were not detected, however after AR in citraconic anhydride proSP-C positive products were distributed specifically, in rough endoplasmic reticulum membranes, Golgi complex membranes, multivesicular bodies and osmiophilic lamellar bodies. The positive proSP-C products also showed lattice-like structures in the alveoli. Thus, the present AR method provides successful pre-embedding immunoelectron microscopy of glutaraldehyde-fixed tissues.

Eumelanin and phaeomelanin contents of depigmented and repigmented skin in vitiligo patients.

BACKGROUND: There are two chemically distinct types of melanin: the red-yellow phaeomelanin and the brown-black eumelanin. Both types of melanin have been detected in human hair, epidermis and cultured melanocytes. OBJECTIVES: In a preliminary study, to quantify levels of both eumelanin and phaeomelanin in depigmented as well as repigmented patches of vitiligo following psoralen plus ultraviolet A (PUVA) therapy. METHODS: We enrolled five patients with vitiligo for this study. We took biopsies from depigmented as well as repigmented lesions after PUVA therapy. The eumelanin and phaeomelanin contents of the skin biopsies were quantified by high-performance liquid chromatography. RESULTS: The mean concentrations in depigmented lesions were 229.4 ng per piece for phaeomelanin and 572 ng per piece for eumelanin (mean phaeomelanin/eumelanin ratio 0.36). In repigmented lesions, the mean concentration of phaeomelanin was 74.8 ng per piece and that of eumelanin was 1657.6 ng per piece (mean phaeomelanin/eumelanin ratio 0.049). CONCLUSIONS: Depigmented lesions showed both types of melanin, and contained a substantial amount of phaeomelanin, whereas repigmented lesions after PUVA showed predominantly eumelanin. We detected melanin in depigmented lesions of vitiligo of 5 years duration, suggesting that some residual melanocytes are still active in depigmented lesions.

Rate constants for the first two chemical steps of eumelanogenesis.

The kinetics of the initial cyclization and redox exchange reactions involved in the eumelanogenic pathway have been studied previously but because of the difficulty of detecting the intermediate cyclodopa by optical means (because its absorbance is in the same range as dopa which is present in excess in the experimental system) no accurate value for the redox exchange reaction has so far been obtained and there is no available analytical methodology that can be applied to the successive first- and second-order reactions involved. We have synthesized cyclodopa and examined the kinetics of the formation of dopachrome following the pulse radiolytic generation of dopaquinone in its presence. From this direct measurement we determined that the rate constant of the reaction between cyclodopa and dopaquinone is 5.3 x 10(6)/M/s. Employing this value in a computational model of the combined cyclization and redox exchange reactions we calculate that the observed kinetics of dopaquinone decay and dopachrome formation are compatible with a cyclization rate constant of 3.8/s.

Melanoma inhibitory activity (MIA) as a serum marker for early detection of post-surgical relapse in melanoma patients: comparison with 5-S-cysteinyldopa.

One of the principal applications of tumour markers is the early detection of recurrent disease in the follow-up of patients. In the study described here, we compared the usefulness of two serum markers for melanoma, 5-S-cysteinyldopa (5-S-CD) and melanoma inhibitory activity (MIA), in the monitoring of postsurgical melanoma patients. A total of 154 serum samples taken from 45 melanoma patients, who underwent surgery of the primary tumour and were under periodical follow-up for 13 to 180 months, were analysed. Serum MIA measurements were performed using an enzyme-linked immunosorbent assay (ELISA), and 5-S-CD levels were determined using high performance liquid chromatography (HPLC). In 72 serum samples taken from a group of 31 non-progressive patients with a median follow-up of 48.5 months, false positive rates of both markers were equally low, being 6.9% (five out of 72) for 5-S-CD and 8.3% (six out of 72) for MIA. In contrast, the sensitivity of MIA at the time point of the first clinical relapse in 14 progressive patients was significantly greater than that of 5-S-CD (0.64 [nine out of 14] versus 0.21 [three out of 14]; P < 0.05). Furthermore, seven patients showed abnormal serum MIA values 4-53 months prior to the clinical detection of metastasis, and the elevated levels were often noted on multiple occasions. These results show that MIA was superior to 5-S-CD in monitoring melanoma patients under periodical follow-up after the primary surgery. Repeated elevation of serum MIA levels may predict the presence of clinically undetectable occult metastases, which warrants further prospective investigations to assess the prognostic significance of serum MIA levels in postsurgical melanoma patients.

Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression: 10 years' experience.

5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. In this study, we measured serum levels of 5-S-CD in 2648 samples taken from 218 patients in order to evaluate the usefulness of this parameter in following melanoma progression and prognosis. 5-S-CD levels were significantly elevated above the upper limit of the normal range (10 nmol/l) in stage IV melanoma patients. The sensitivity of elevated serum 5-S-CD levels in detecting distant metastasis was 73%, while the specificity was 98% and the positive predictive value 94%. The sensitivity was improved to 77% when cases of amelanotic melanoma were excluded. Patients without metastases had elevated 5-S-CD values in 5% of the 1480 serum samples. Changes in serum 5-S-CD levels were followed during disease progression until the end stage in 49 patients. In 33% of the patients, elevation of serum 5-S-CD levels preceded clinical detection of visceral metastases, and in 37% elevation of 5-S-CD levels occurred at the same time as visceral metastasis. Patients with elevated 5-S-CD levels before or after surgical treatment had significantly shorter survival times than those with normal levels. These results show that the level of 5-S-CD in the serum is a sensitive and specific marker in predicting distant metastases. Elevated serum levels of 5-S-CD, before or after surgical treatment, is associated with a poor prognosis.

Heart rate variability in normotensive healthy children with aging.

Although the heart rate variability (HRV) values in adults decrease with aging, those in children show a variety of changes. The present study was designed to investigate the relationship between HRV and aging, physique and blood pressure in 70 healthy male school children, between 6 and 12 years of age. The subjects were divided into 3 age groups (6-7, 8-9 and 10-12 years) and 3 other groups according to physique (thin, under -10%; normal, -10-20% and obese, over 20% of obesity index). After recording a 24-h ambulatory electrocardiograph, HRV was determined spectrally, using 3 components: the total-frequency (TF) component (0.01 to 0.5 Hz), the low-frequency (LF) component (0.04 to 0.15 Hz), the high-frequency (HF) component (0.15 to 0.5 Hz) and also a two component ratio (LF/HF). The HRV values between the 3 age groups had a significant effect on TF, LF and LF/HF during the 24-h period, with the values increasing with age. The HRV values between the 3 physique groups had no significant effect. Therefore, changes in HRV in school children are affected by age and not physique. It is possible that the increase in HRV values with age is caused by the development of the autonomic nervous system.

5-S-cysteinyldopa as diagnostic tumor marker for uveal malignant melanoma.

PURPOSE: To evaluate the clinical significance of 5-S-cysteinyldopa (5-S-CD), a major intermediate in melanin synthesis, as a potential diagnostic tumor marker for uveal malignant melanoma. METHODS: The levels of 5-S-CD in the serum were measured by high-performance liquid chromatography in 16 patients with primary uveal melanoma. The levels of 5-S-CD were also measured in both aqueous and vitreous humor in 10 patients with uveal melanoma. The serum of healthy volunteers and patients with skin diseases other than melanoma, and the intraocular fluids of patients with cataract and vitreoretinal diseases were used as controls. RESULTS: Serum concentrations of 5-S-CD in patients with uveal melanoma in the absence of extraocular metastases were close to those of controls; however, serum concentrations of 5-S-CD were significantly elevated in patients with extraocular metastases of melanoma. Concentrations of 5-S-CD in the intraocular fluids, especially vitreous humor, were higher in patients with uveal melanoma than in controls. CONCLUSIONS: 5-S-CD in intraocular fluids may serve as a useful biochemical marker for the diagnosis of uveal melanoma. Serum 5-S-CD may contribute to the assessment of the presence and progression of extraocular metastases in patients with uveal melanoma.