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Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill.

BACKGROUND: In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. RESULTS: The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl) carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. CONCLUSIONS: Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

Adenylyl Cyclase Inhibitors↗

Iron-induced accumulation of lipofuscin-like fluorescent pigment in the retinal pigment epithelium.

PURPOSE: One of the most prominent changes that occurs in the retinal pigment epithelium during senescence is the progressive accumulation of the autofluorescent pigment lipofuscin. Experiments were conducted to evaluate the role of nonenzymatic oxidation of photoreceptor outer segments in retinal pigment epithelium lipofuscin formation. METHODS: Albino Fischer rats were given intravitreal injections of ferrous sulfate, a catalyst that promotes nonenzymatic lipid oxidation. At 2 hours, 24 hours, and 7 days after ferrous sulfate administration, the retinas were examined with fluorescence microscopy to assess the formation of fluorescent products. At these same time intervals, organic solvent extracts of the retinas and retinal pigment epithelium-choroid complexes were prepared. The extracts were analyzed with thin layer chromatography to assay for the presence of soluble fluorophores. The ultrastructural appearances of the retinas were examined at the same time points. RESULTS: At both 2 hours and 24 hours after the ferrous sulfate treatment, the photoreceptor outer segments displayed a yellow-green fluorescence emission that was not present in untreated eyes. Associated with this in situ fluorescence were a number of blue-green emitting fluorophores in organic solvent extracts that did not correspond to any of the fluorophores extracted from the retinal pigment epithelium of old animals. One week after the ferrous sulfate treatment, the photoreceptor cells had degenerated and the retinal pigment epithelium contained large amounts of an autofluorescent pigment with a golden-yellow emission typical of lipofuscin. The iron-induced fluorophores could not be extracted from this pigment into either chloroform or dichloromethane. CONCLUSIONS: The initial fluorophores that were formed as a result of nonenzymatic oxidation of outer segment components did not appear to be the same as those responsible for retinal pigment epithelium lipofuscin fluorescence. However, after the oxidized outer segments were phagocytosed by the retinal pigment epithelium, the latter cells became filled with a yellow-emitting fluorescent pigment that was similar in its fluorescence properties to lipofuscin. These observations suggest that lipofuscin fluorophores are not direct products of nonenzymatic lipid oxidation. However, some of these oxidation products may be modified after uptake by the retinal pigment epithelium to form insoluble lipofuscin fluorophores.

Animals↗

Metabolomic and structural signatures of pigmented and non-pigmented Himalayan rice landraces.

BACKGROUND: This study investigated the anti-oxidant properties, starch composition, pasting behavior, structural properties, textural properties and non-targeted metabolomic profiles of pigmented and non-pigmented rice landraces as potential next-generation functional food ingredients. RESULTS: Pigmented rice demonstrated 1.34 times more anti-oxidant activity as compared to non-pigmented rice. Pigmented landraces showcased superior nutritional and functional attributes, including higher total dietary fiber and starch content. Fourier-transform infrared (FTIR) analysis revealed distinct molecular signatures with enhanced peak transmittance, while X-ray diffraction (XRD) indicated greater crystallinity ranging from 36-44.3% in pigmented rice compared with 30-40% in non-pigmented rice, suggesting improved digestibility and processing versatility. Pigmented rice recorded less amylose content hence tended to possess increased adhesiveness values whereas non-pigmented rice revealed greater amylose content hence was coupled with greater hardness values. Field-emission scanning electron microscopy (FE-SEM) images revealed that pigmented rice had densely packed and polygonal starch granules whereas non-pigmented rice had loosely packed starch granules with intergranular voids. Untargeted gas chromatography-mass spectrometry (GC-MS) profiling identified 84 metabolites, including unique compounds such as 3,3-dimethylbutanol and ethanoic acid, along with shared metabolites such as sucrose and linoleic acid, highlighting notable biochemical diversity. Multivariate statistical analyses using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping further differentiated the metabolomic landscapes, with variable importance in the projection (VIP) scores identifying key bioactive contributors. CONCLUSION: Pigmented rice landraces exhibited significant functional and nutritional advantages, making them promising candidates for functional food development and nutritional improvement programs. These findings support their potential role in advancing sustainable and health-oriented food systems. © 2026 Society of Chemical Industry.

Oryza↗

Comparative chemical characterization of pigmented and less pigmented cell walls of Alternaria tenuissima.

Alternaria tenuissima, the parasitic fungus, was obtained from the pruned upper-cut surfaces of mulberry stems. This fungus contains dark pigment because of the presence of melanin in the cell wall. To obtain less-pigmented cell walls, this fungus was grown under dark condition. When the pigmented and less-pigmented cell walls were chemically analyzed, no differences were observed in amino-acid composition, hexoses, or pentoses. However, in pigmented cell walls, higher contents of melanin (2.6%) were found than in less-pigmented cell walls (0.3%). Interestingly, a significant difference was observed in the relative fatty-acid compositions between these two types of cell walls. Among the major fatty acids, there were increased concentrations of tetradecanoic acid (C14:0), hexadecanoic acid (C16:0), 9-hexadecenoic acid (C16: 1,Delta 9), and 9-octadecanoic acid (C18:1,Delta 9) and a concomitant decrease in 9,12-octadecadienoic acid (C18:2,Delta 9,12) in less-pigmented compared with pigmented cell walls. This difference in fatty-acid composition may be related to the higher percentage of melanin in the pigmented than the less-pigmented cell walls. Lesser amounts of 9,12-octadecadienoic acid in less-pigmented cell walls may have been caused by the growth of the fungus under environmental stress conditions. An interesting observation was the presence in pigmented cell walls only of methyl-substituted fatty acids with carbon numbers C14 to C17, but their occurrence could not be ascertained in the present study.

Alternaria↗

Development of pigment cells in the brain of ascidian tadpole larvae: insights into the origins of vertebrate pigment cells.

In vertebrates, melanins produced in specialized pigment cells are required for visual acuity, camouflage, sexual display and protection from ultra violet (UV) radiation. There are three pigment cell types that are classified based on their distinct embryonic origins. Retinal pigment epithelium (RPE) cells originate from the outer layer of the optic cup. Pigment cells of the pineal organ are formed from the developing diencephalon. Melanocytes are derived from the neural crest unique to vertebrate embryos. Some of these pigment cells also play roles that are independent of the activity of tyrosinase, the key melanogenesis enzyme, or melanin: production of substrate(s) for catecholamine synthesis, maintenance of endolymph composition in the cochlea, maintenance of photoreceptor cells in the retina and retinoid metabolism essential for the visual cycle. To deduce the evolutionary origins of vertebrate pigment cells and a possible archetypal genetic circuitry, which may have been modified and utilized to generate multiple pigment cell types, comparison of developmental mechanisms of pigment cells between vertebrates and closely related invertebrate ascidians are proposed to provide useful information. The tadpole-type larva of ascidians possesses two melanin-containing pigment cells, termed the otolith and ocellus pigment cells, in the brain that are believed to be required for photo- and geotactic responses during swimming. In this review, current knowledge on the development of the two ascidian pigment cells is summarized, i.e. complete cell lineage, structure and expression of genes encoding two melanogenesis enzymes, and molecular developmental mechanisms involving BMP-CHORDIN antagonism, and possible evolutionary relationships between ascidian and vertebrate pigment cells are discussed.

Animals↗

Pigment gallstones form as a composite of bacterial microcolonies and pigment solids.

Although previous studies have suggested that bacteria may contribute to pigment gallstone formation, the current experiments provide evidence that bacteria have a central role in this process. The studies included scanning electron microscopy (SEM) of gallstones, measurements of bacterial adherence to gallstones in vitro, and determination of glycocalyx elaboration by biliary bacteria. Gallstones from 85 patients were studied under SEM. Twenty-five (78%) of 32 pigment stones had evidence of bacterial microcolonies throughout the interior of the stones. Bacteria were absent from the interior of all 35 cholesterol stones studied. Composite stones (stones with separate pigment and cholesterol portions) showed evidence of bacteria within the pigment portions in 14 (78%) of 18 cases. Biliary bacteria adhered to the surface of pigment gallstones in vitro in 35 (90%) of 39 cases, compared with three (8%) of 39 cholesterol stones. Glycocalyx was elaborated by bacteria isolated from nine (82%) of 11 patients with either pigment or composite gallstones. One (33%) of three bacterial species from patients with cholesterol gallstone disease produced glycocalyx. These studies indicate that most pigment gallstones obtained from patients in Western cultures form as a composite of bacteria, bacterial glycocalyx, and pigment solids. Bacteria were found in the majority of black as well as brown pigment stones. These findings serve as the basis of a new theory of pigment stone formation in which bacteria and glycocalyx are postulated to be responsible for the precipitation and subsequent agglomeration of bilirubin pigment. These results also suggest that sepsis is more common in pigment gallstone disease because the stones can serve as a sanctuary for bacteria.

Adult↗

[Comparative study of lipid peroxidation in the eye pigment epithelium of pigmented and albino animals].

The induction of lipid peroxidation in the eye pigment epithelium of pigmented rabbits by the Fe2+ + ascorbate and xanthine--xanthine oxidase systems did not result in accumulation of malonic dialdehyde. In albino rabbits the lipid peroxidation of the non-pigmented pigment epithelium and retina occurred at a high rate under the same conditions. The rate of lipid peroxidation also showed an increase after removal of melanoprotein granules from the pigmented pigment epithelium. The latter inhibited the rate of lipid peroxidation in the eye retina. In albino animals the rate of lipid peroxidation in a mixture of the tow tissues (i.e. pigment epithelium and retina) is almost 4 times that in the pigmented animals. Consequently, the pigmented pigment epithelium of the eye is much more resistant to the effect of prooxidant systems as compared to the non-pigmented one. It is assumed that one of the main functions of the melanoprotein granules in the eye pigment epithelium cells is their protective effect.

Albinism↗

The distribution of calcium salt precipitates in the core, periphery and shell of cholesterol, black pigment and brown pigment gallstones.

Calcium bilirubinate, palmitate, carbonate and phosphate have been identified in the cores of cholesterol and pigment gallstones, suggesting a role for precipitated calcium salts in the early events of gallstone formation. Previous studies that compared the calcium salt contents of cholesterol and pigment stones required destruction of gallstone structure. We have used scanning electron microscopy with windowless energy-dispersive x-ray microanalysis to determine the prevalence of calcium salts in a series of cholesterol (n = 105), black pigment (n = 35) and brown pigment (n = 6) gallstones obtained from 146 consecutive patients undergoing cholecystectomy. These techniques provide specific identification of cholesterol and individual calcium salts as they occur within the core, periphery and shell of gallstones without destroying stone structure. Calcium precipitates more than 0.5 micron in diameter can be detected in a cholesterol background at a detection limit of 0.01% by weight. Calcium salts were detected in the centers of 88% of cholesterol and 100% of black (p < 0.05 vs. cholesterol) and brown pigment stones. Calcium bilirubinate was identified in the cores of 54% of cholesterol and in all pigment stones (p < 0.001 black pigment vs. cholesterol). Calcium palmitate was detected in all brown pigment stones, in 39% of cholesterol stones (p < 0.001 vs. brown pigment) and in 31% of black stones (p < 0.01 vs. brown pigment). Peripheral calcium salts were detected less in cholesterol (19%) than in black or brown stones (100%, p < 0.05). Fourteen percent of cholesterol and black pigment stones were surrounded by shells containing mostly calcium carbonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Binding of 14C-imipramine by pigmented and non-pigmented tissues.

When pigmented and non-pigmented rabbit irides were incubated with various concentrations of 14C-imipramine at equilibrium (120 min), the accumulation of the drug by the pigmented iris was 1.5 times as great as that by the non-pigmented iris. The accumulated drug is lost from both types of irides in a complex fashion. However, even after 120 min of washing, the differences in accumulation remain nearly constant. When accumulation of the drug in the non-pigmented iris was analyzed by discontinuous sucrose density gradient, it was observed that the drug was bound mainly by the low density sucrose fractions where the synaptosomes separate. On the contrary, in the pigmented iris approximately 70% of the drug was found in the melanin-containing fraction. The homogenate from the substantia nigra accumulated 1.5 times more than that from the human brain cortex. The affinity of the drug for bovine iris melanin granules and the synthetic L-dopa melanin was 9.9 X 10(5) M-1 and 3.8 X 10(3) M-1, respectively. On the rabbit iris sphincter muscles, imipramine was evaluated for antimuscarinic effects. The apparent dissociation constants, KB values, for the antagonist in the non-pigmented and pigmented iris were 1.7 X 10(-7) M and 3.8 X 10(-6) M, respectively. The low antimuscarinic activity in the pigmented iris is attributed to the loss of the drug to the pigment. On this basis, relevancy of the drug binding by pigmented tissues to the effects of this tricyclic drug is discussed.

Animals↗

Effects of the actin-stabilizing drug, jasplakinolide, on pigment granule motility in isolated retinal pigment epithelial (RPE) cells of green sunfish, Lepomis cyanellus.

The retinal pigment epithelium (RPE) of teleosts contains pigment granules that migrate in response to changes in light condition. Dissociated, cultured RPE cells in vitro can be triggered to aggregate or disperse pigment granules by the application of cAMP or dopamine, respectively. Previous research using the actin-disrupting drug, cytochalasin D, suggested that pigment granule motility is actin dependent. To further examine the role of actin in pigment granule motility, we tested the effects of the actin-stabilizing drug, jasplakinolide, on pigment granule motility. Pigment granules in previously dispersed RPE cells remained dispersed after jasplakinolide exposure (0.1-1 microM), but the drug halted movement of most pigment granules and stimulated rapid bi-directional movements in a small subset of granules. Jasplakinolide also blocked net pigment granule aggregation and interfered with the maintenance of full aggregation. Although jasplakinolide did not block pigment granule dispersion, it did alter the motility of dispersing granules compared to control cells; rather than the normal saltatory, primarily centrifugal movements, granules of jasplakinolide-treated cells demonstrated slow, creeping centrifugal movements and more rapid bi-directional movements. Jasplakinolide also altered cell morphology; the length and thickness of apical projections increased, and enlarged, paddle-like structures, which contained F-actin appeared at the tips of projections. Actin antibody labeling of jasplakinolide-treated cells revealed a more reticulated network of actin compared to antibody-labeled control cells. These results indicate that jasplakinolide-induced disruption of the actin network compromises normal pigment granule dispersion and aggregation in isolated RPE cells, thus providing further evidence that these movements are actin dependent.

Actins↗

[Studies of Nocardia pellegrino SN 5108 pigment mutants: reasons for differences in pigmentation (author's transl)].

Yellow and white mutants of the strains Nocardia pellegrino SN 5108 R have been isolated. Regarding their morphological and physiological properties, the mutants are identical with the wild type bacteria with the exception of their pigmentation and lipid composition. However, the pigment composition (number, Rf-values and spectra of the pigment components) of the yellow mutant is identical with that of the wild type; as a consequence, the modified pigmentation of the yellow mutant cannot be explained by an altered pigment synthesis. The wild type cells and the mutant SN 5108 G contain three main pigment components designated as I, II and III. Components II and III posses a marked indicator character and show a bathochromic shift in solutions of pH 12 or higher. Components II and III contain functional groups which are able to react with acetic acid yielding acetylated products; after acetylating, no bathochromic shift in alkali occurs. Intact cells of the wild type retain their orange-red pigmentation in buffer solution with a pH-value of 12 or higher. Cells of the yellow mutant, however, change the yellow color immediately after the alkali treatment to orange-red; this new color is identical with that of the wild type and can be changed to yellow by placing the cells into 1 N HCl. Regarding these facts it seems to be very probable that the functional groups of the pigment components II and III are differently bound in the wild type and mutant cells. In the mutant, they are accessible to OH- ions yielding a bathochromic shift while in the wild type cells, OH- ions are unable to provoke this shift. It seems to be also probable that different lipids in the two strains are responsible for the binding of the pigments. So far known, this is the first observation about the occurence of pigment mutants with an altered pigment binding site in the cells.

Binding Sites↗

Stimulation of distinct D2 dopaminergic and alpha 2-adrenergic receptors induces light-adaptive pigment dispersion in teleost retinal pigment epithelium.

In the retinal pigment epithelium (RPE) of lower vertebrates, melanin pigment granules aggregate and disperse in response to changes in light conditions. Pigment granules aggregate into the RPE cell body in the dark and disperse into the long apical projections in the light. Pigment granule movement retains its light sensitivity in vitro only if RPE is explanted together with neural retina. In the absence of retina, RPE pigment granules no longer move in response to light onset or offset. Using a preparation of mechanically isolated fragments of RPE from green sunfish, Lepomis cyanellus, we investigated the effects of catecholamines on pigment migration. We report here that 3,4-dihydoxyphenylethylamine (dopamine) and clonidine each mimic the effect of light in vivo by inducing pigment granule dispersion. Dopamine had a half-maximal effect at approximately 2 nM; clonidine, at 1 microM. Dopamine-induced dispersion was inhibited by the D2 dopaminergic antagonist sulpiride but not by D1 or alpha-adrenergic antagonists. Furthermore, a D2 dopaminergic agonist (LY 171555) but not a D1 dopaminergic agonist (SKF 38393) mimicked the effect of dopamine. Clonidine-induced dispersion was inhibited by the alpha 2-adrenergic antagonist yohimbine but not by sulpiride. These results suggest that teleost RPE cells possess distinct D2 dopaminergic and alpha 2-adrenergic receptors, and that stimulation of either receptor type is sufficient to induce pigment granule dispersion. In addition, forskolin, an activator of adenylate cyclase, induced pigment granule movement in the opposite direction, i.e., dark-adaptive pigment aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Fluorescent pigment accumulation in retinal pigment epithelium of antioxidant-deficient rats.

A yellow autofluorescent pigment, generally thought to be indicative of membrane autoxidation, was found to accumulate in the retinal pigment epithelium (RPE) of rats maintained for 32 weeks on diets producing physiological antioxidant deficiency. The largest build-up of fluorescent pigment occurred in rats fed a diet high in polyunsaturated fatty acids (PUFAs) and deficient in alpha-tocopherol (vitamin E), selenium, sulfur-containing amino acids, and chromium. These latter four nutrients have all been implicated in maintaining the antioxidant status of tissues, whereas PUFAs are pro-oxidants. Dietary supplementation with methionine and chromium significantly reduced the amount of fluorescent pigment accumulated in the RPE. Supplementation with all four nutrients further reduced the amount of fluorescent pigment to a very low level. Rats maintained on a normal laboratory diet, relatively low in PUFAs and presumably adequate in other nutrients, accumulated relatively small amounts of fluorescent pigment in the RPE. Of all tissues in the retina and choroid, the autofluorescent pigment was found to be almost entirely restricted to the RPE. The autofluorescence produced in the RPE by antioxidant deficiency was more concentrated than that produced in the testes, kidney, intestine, and heart. This suggests that the RPE is particularly sensitive to physiological antioxidant deficiencies. The increased fluorescent pigment build-up in the RPE of antioxidant-deficient rats appears to correlate with a decreased RPE melanin content. Similar changes in pigmentation have been reported to occur in human RPE with age and in dominantly inherited retinitis pigmentosa. Thus, with respect to its effect on RPE pigmentation, antioxidant deficiency appears to mimic aging and possibly some aspects of one type of retinitis pigmentosa.

Amino Acids, Sulfur↗

Turn-specific and pigment-dependent differences in the stria vascularis of normal and gentamicin-treated albino and pigmented guinea pigs.

The aims of the present study were to determine which structures in the stria vascularis (SV) may depend upon the presence of pigmented melanocytes both for normal morphology and for the expression of gentamicin ototoxicity in the inner ear. These pigment-dependent influences were inferred through comparisons of the SV in pigmented guinea pigs and in albinos containing nonpigmented melanocytes. Results were obtained from 6 albino and 8 pigmented guinea pigs given gentamicin, and from 3 albino and 3 pigmented control animals not receiving the drug. One-month old animals received gentamicin daily (100 mg/kg) for 14 days and recovered for an additional 14 days before being prepared for electron microscopy. The SV from each of the 4 cochlear turns was analyzed using stereological point counting procedures. In control animals, differences were found in the higher cochlear turns, where volume density for the marginal cells in albinos was abnormally large (turns 3 and 4), while the volume density for intermediate cells (melanocytes) was abnormally small (turn 3). Cell volume estimates for the intermediate cells were significantly smaller in the albino than pigmented control animals in the higher cochlear turns, indicating that functional abnormalities may be found in the albino cochlea. In animals exposed to gentamicin, marginal cell volume density was reduced significantly in turn 4 of albinos, but not in any region of the pigmented inner ears. Radial area of SV and estimates of the absolute volumes for marginal cells in albinos given gentamicin also were significantly reduced in turn 1 compared to their controls; such differences were not observed in the pigmented animals. The results indicate that marginal cell size is significantly reduced in albino but not pigmented animals 14 days after gentamicin exposure, and further suggest a role of pigmented melanocytes in ameliorating gentamicin-induced cochlear damage.

Animals↗

Formation of halogenated aryl-polyene (xanthomonadin) pigments by the type and other yellow-pigmented strains of Xanthomonas maltophilia.

Based upon visible electronic absorption spectra and mass spectra, yellow-pigmented strains of Xanthomonas maltophilia, including the type strain (ICPB 2648-67 = ATCC 13637) of this species, were shown to produce aryl-polyene (xanthomonadin) pigments. These pigments, which usually occurred in very small quantities, were isolated and studied as isobutyl derivatives. The most common X. maltophilia pigment (Pigment 1), which occurred in 8 of the 12 yellow-pigmented strains examined, was shown to be a monochlorinated aryl-hexaene, molecular ion (M+) 384, with the empirical formula C23H25O3Cl. Pigment 3, M+ 376, which was found as the major pigment in one strain of X. maltophilia and as a minor component in two other strains, probably is the same non-halogenated aryl-heptaene reported previously in Xanthomonas populi and X. juglandis. Although all of these X. maltophilia strains originated from medical rather than phytopathogenic environments, the occurrence of these xanthomonadin pigments in non-phytopathogenic strains emphasizes the chemotaxonomic significance of these aryl-polyene pigments in the genus Xanthomonas.

Pigments, Biological↗

Pigmented mammary Paget disease and pigmented epidermotropic metastases from breast carcinoma.

Pigmented mammary Paget disease is a rare clinicopathologic variant of mammary Paget disease. It has been described in female and male patients with intraductal mammary carcinoma extending to the epidermis of the nipple and areola through a lactiferous duct. Pigmented cutaneous metastases from breast carcinoma are uncommon variants of epidermotropic metastatic breast carcinoma. All these lesions may mimic malignant melanoma clinically and histopathologically. From a histopathologic point of view, involvement of the dermoepidermal junction by neoplastic cells of the mammary carcinoma seems to be a prerequisite for development of the clinical pigmentation. We report three examples of pigmented mammary Paget disease and six cases of pigmented epidermotropic metastases from breast carcinoma, which were studied from both the histopathologic and immunohistochemical points of view. Two cases of pigmented mammary Paget disease and all cases of pigmented epidermotropic metastatic breast carcinoma showed the proliferation of dendritic melanocytes arranged as solitary units along the dermoepidermal junction and intermingled with the neoplastic cells of the mammary carcinoma in the superficial dermis. In one case of pigmented mammary Paget disease, there was abundant melanin within the cytoplasm of the Paget cells, but an increased number of melanocytes could not be demonstrated. Local production of melanocytic chemotactic factor by neoplastic cells of the mammary carcinoma when they reach the dermoepidermal junction has been postulated as the cause of the melanocytic proliferation and clinical hyperpigmentation of these epidermotropic breast carcinomas. Another possibility is the phagocytosis or transfer of melanin from melanocytes to the intraepidermal neoplastic cells of the breast carcinoma. Pigmented mammary Paget disease and pigmented epidermotropic metastatic breast carcinoma should be differentiated from melanoma clinical and histopathologically.

Adult↗

Effects of drugs on cellular proliferation in cultured iris pigment epithelial cells and retinal pigment epithelial cells.

In this study, iris and retinal pigment epithelial cells were cultured from porcine and various drugs including methionine-enkephalin, isoproterenol, dibutyryl cAMP, endothelin-1, dexamethasone and phorbol 12-myristate 13-acetate (PMA) were used to investigate their effects on both cellular proliferation in cultured porcine iris and retinal pigment epithelial cells. Cellular proliferation was estimated with 3H-thymidine uptake. It is indicated that both pigment epithelial cells possess epithelial-like morphology and abundant pigment granules in cells obviously. Following the iris pigment epithelial cells being treated with endothelin-1, the 3H-thymidine uptake in the cells was increased to 126% as compared with the control. However, the cellular proliferation was decreased to 83% when the cells were treated with isoproterenol. In the case of methionine-enkephalin, dibutyryl cAMP, dexamethasone and phorbol 12-myristate 13-acetate (PMA), the thymidine uptake in the iris pigment epithelial cells was not affected by above drugs. In the retinal pigment epithelial cells, the 3H-thymidine uptakes were increased to 145% and 146% when the cells were incubated with methionine-enkephalin, and isoproterenol, respectively. In the presence of dibutyryl cAMP, dexamethasone and phorbol ester (PMA), the cellular proliferation was inhibited to 83%, 73% and 85% respectively. However, endothelin-1 did not affect the cellular proliferation in retinal pigment epithelial cells. These results show that the morphological shapes of iris pigment epithelial cells are similar to retinal pigment epithelial cells. However, the cellular proliferation in both cells may be regulated by distinct mechanisms.

Animals↗