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Differences in antimicrobial susceptibility of pigmented and unpigmented colonial variants of Mycobacterium avium.

Unpigmented colonial variants were isolated from pigmented Mycobacterium avium isolates recovered from patients with acquired immunodeficiency syndrome and the environment. The variants were interconvertible: the rate of transition from unpigmented to pigmented type was 4.0 x 10(-5) variants per cell per generation. The unpigmented variants were more tolerant to antibiotics, especially beta-lactams, and Cd2+ and Cu2+ salts than were their pigmented parents. Both pigmented and unpigmented variants of the strains produced beta-lactamase, although beta-lactamase did not appear to be a determinant of beta-lactam susceptibility. Pigmented variants grew more rapidly in a number of commonly used mycobacterial media, were more hydrophobic, and had higher carotenoid contents than their unpigmented segregants.

Acquired Immunodeficiency Syndrome↗

Evaluation of aid to diagnosis of pigmented skin lesions in general practice: controlled trial randomised by practice.

OBJECTIVES: To determine whether an aid to the diagnosis of pigmented skin lesions reduces the ratio of benign lesions to melanomas excised in general practice. DESIGN: Controlled trial randomised by practice. SETTING: General practices in Perth, Western Australia. PARTICIPANTS: 468 general practitioners in 223 practices. INTERVENTIONS: Intervention practices were given an algorithm and instant camera to assist with the diagnosis of pigmented skin lesions. All practices were given national guidelines on managing melanoma. MAIN OUTCOME MEASURES: Ratio of benign pigmented lesions to melanomas excised. Analyses conducted with and without inclusion of seborrhoeic keratoses. RESULTS: At baseline the ratios of benign to malignant lesions were lower in the intervention group than in the control group. During the trial period the ratios were higher in the intervention group (19:1 v 17:1 without seborrhoeic keratoses and 29:1 v 26:1 with seborrhoeic keratoses). After adjustment for patients' age, sex, and socioeconomic status, the ratio was 1.02 times higher (95% confidence interval 0.68 to 1.51, P = 0.94) in the intervention group when seborrhoeic keratoses were not included and 1.03 times higher (0.71 to 1.50, P = 0.88) when seborrhoeic keratoses were included. General practitioners in the intervention group were less likely than those in the control group to excise the most recent pigmented skin lesion they managed (22% v 48%, P < 0.001) and to refer the patient to a specialist (16% v 27%, P = 0.06). CONCLUSIONS: Provision of the algorithm and camera did not decrease the ratio of benign pigmented skin lesions to melanomas excised by general practitioners.

Algorithms↗

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation.

Aluminum Silicates↗

Prodiginine (prodigiosin-like) pigments from Streptomyces and other aerobic Actinomycetes.

About 95 microorganisms, mainly streptomycetes, were examined for prodiginine pigments. The test methods, including some media for stimulating pigment production, are given. All nine strains which produced prodiginine pigments were characterized and the pigments identified. The results were used to propose structures for five prodigiosin-like pigments from actinomycetes reported in the literature between 1947 and 1964. Streptoverticillium sp. 26-1 furnished good yields of butylcycloheptylprodiginine (I), whose antimicrobial activity is given.

Actinomycetales↗

The effect of pH and amino acids on conidiation and pigment production of Monascus major ATCC 16362 and Monascus rubiginosus ATCC 16367 in submerged shaken culture.

Monascus major ATCC 16362 and Monascus rubiginosus ATCC 16367 were cultivated aerobically on media containing nitrate or ammonium as nitrogen source to which the following modifications were made: (1) pH adjusted to 2.5 before sterilization; (2) addition of yeast extract; (3) addition of amino acids in identical proportions and concentrations to those found in yeast extract; (4) adjustment of pH to 2.5 after addition of amino acids. The addition of amino acids in the form of yeast extract increased mycelium formation and reduced conidiation and pigment production. The addition of an amino acid mixture did not increase mycelium formation to the same extent as yeast extract but increased the number of conidia, while pigment production was reduced, especially when nitrate was the nitrogen source. As the amino acids are taken up after conidial formation has started, it would appear that it is not the amino acids themselves which are directly responsible for the induction of conidiation. The addition of amino acids inhibits nitrate and ammonium uptake suggesting the need for an early intracellular nitrogen limitation to induce conidiation. Lowering the pH inhibits the formation of conidia and increases pigment production; also the effect of amino acid addition is totally annulled. The pH of the medium is all important in regulating the formation of conidia and pigment production. The possible effects of the pH on the uptake of certain medium components is discussed, as well as their possible control of certain metabolic pathways which ultimately determines the availability of intermediates for conidiation and pigment production.

Aerobiosis↗

Chlamydomonas reinhardtii in the landscape of pigments.

This review focuses on the biosynthesis of pigments in the unicellular alga Chlamydomonas reinhardtii and their physiological and regulatory functions in the context of information gathered from studies of other photosynthetic organisms. C. reinhardtii is serving as an important model organism for studies of photosynthesis and the pigments associated with the photosynthetic apparatus. Despite extensive information pertaining to the biosynthetic pathways critical for making chlorophylls and carotenoids, we are just beginning to understand the control of these pathways, the coordination between pigment and apoprotein synthesis, and the interactions between the activities of these pathways and those for other important cellular metabolites branching from these pathways. Other exciting areas relating to pigment function are also emerging: the role of intermediates of pigment biosynthesis as messengers that coordinate metabolism in the chloroplast with nuclear gene activity, and the identification of photoreceptors and their participation in critical cellular processes including phototaxis, gametogenesis, and the biogenesis of the photosynthetic machinery. These areas of research have become especially attractive for intensive development with the application of potent molecular and genomic tools currently being applied to studies of C. reinhardtii.

Animals↗

Semiological value of ABCDE criteria in the diagnosis of cutaneous pigmented tumors.

OBJECTIVE: The aim of this study was to evaluate the semiological value of the so-called ABCDE criteria in the differential diagnosis of pigmented tumours. Aside from the classical ABCD criteria, an E criterion for 'enlargement' is studied. MATERIAL AND METHODS: Records from melanoma patients were obtained from a melanoma database prospectively including patients treated for melanoma in our department since 1992; 460 files were found informative for this study. A prospective control group was established including 680 cases of benign pigmented tumors. All cases included in the study were histopathologically controlled in our dermatopathology unit. Records of ABCDE, i.e. corresponding to asymmetry, irregular borders, irregular coloration, diameter > or = 6 mm and enlargement, were codified as present or absent in every case. Data were statistically compared for every individual criterion with the chi 2 test and for the number of criteria present in melanoma versus other pigmented tumors with Student's t test. RESULTS: Significant differences were observed for all individual criteria (p < 0.001) between melanomas and common nevi. Significant differences were also observed for B, C and E criteria between melanomas and atypical nevi. The sensitivity of the individual criteria for the diagnosis of melanoma was 57, 57, 65, 90 and 84% for ABCDE, respectively. The specificity of the individual criteria for the diagnosis of melanoma versus other pigmented tumors was 72, 71, 59, 63 and 90% for ABCDE, respectively. The number of criteria present was significatively different between common nevi (1.24 +/- 1.26) and melanomas (3.53 +/- 1.53; p < 0.001) and between common nevi and atypical nevi (3.62 +/- 0.83, p < 0.001), but no significant difference was found between melanomas and atypical nevi. Sensitivity and specificity of diagnosis of melanoma are 89.3 and 65.3% if 2 criteria are present. Sensitivity and specificity of diagnosis of melanoma are 65.5 and 81% if 3 criteria are present. CONCLUSION: The so-called ABCD criteria have a good semiological value in the differential diagnosis of pigmented tumors. Addition of an E criterion for enlargement optimizes sensitivity and specificity of diagnosis.

Diagnosis, Differential↗

Genodermatosis with reticulate, patchy and mottled pigmentation of the neck--a clue to rare dermatologic disorders.

Reticulate pigmentation of the neck is a common finding in numerous genodermatoses and acquired diseases. As the neck is readily accessible to medical inspection, it may serve as a diagnostic window for various dermatoses. Several entities out of the spectrum of ectodermal dysplasia present with reticulate or mottled pigmentation on the upper trunk and neck. The most impressive genodermatoses with punctate and reticulate pigmentation affecting the neck are the Naegeli-Franceschetti-Jadassohn syndrome, dermatopathia pigmentosa reticularis and dyskeratosis congenita. Reticulate pigmented anomaly of the flexures and lentiginosis, disorders of cornification and related entities are further genodermatoses which may involve the neck. In our review we have integrated inherited dermatoses which do not obligatorily affect the neck but have been well documented to do so. Our work should give the clinician a checklist on genodermatoses which may produce reticulate and mottled pigmentation on the neck.

Humans↗

Electro-oculography in pigment dispersion syndrome.

Clinical data and the common embryological origin of the pigment epithelium of the iris and retinal pigment epithelium suggest that the latter may be involved in the pigment dispersion syndrome (PDS). In our study functional changes of the retinal pigment epithelium were evaluated by electro-oculography in 10 PDS patients, 10 patients with chronic open-angle glaucoma (COAG) and 10 normal subjects. The mean dark-trough latency and Arden ratio for the PDS group were significantly lower than those of the COAG and control groups. Analysis of the Arden ratios based on the Kruskall-Wallis test revealed that 30% of the PDS values were subnormal with respect to the control group mean -1 SD. These results indicate primary involvement of the retinal pigment epithelium in PDS.

Adult↗

Effect of ethanol on biliary unconjugated bilirubin and its implication in pigment gallstone pathogenesis in humans.

Though some epidemiological investigations support the association between pigment gallstone formation and chronic alcoholism with cirrhosis, little attention has been paid to the influence of alcohol itself on biliary bilirubin secretion, so that the pathogenesis of pigment cholelithiasis in alcoholics is hitherto unknown. On different days we intravenously administered ethanol (0.7 g/kg body weight), diluted with 500 ml of saline, or saline alone to 6 non-obese patients with an indwelling T tube and reestablished enterohepatic bile circulation. At the time of the investigation bile cultures were negative for aerobic and anaerobic bacteria. Ethanol significantly increased biliary unconjugated bilirubin in respect to control values. The phenomenon reached a maximum 2 h after alcohol infusion when the value of unconjugated bilirubin averaged 2.37 +/- 0.30% of total bilirubin in contrast to 0.65 +/- 0.14% in control conditions (p less than 0.01), and subsided 6 h after the end of ethanol infusion. Since increased amounts of biliary unconjugated bilirubin predispose to pigment stone formation, it can be speculated that alcohol contributes to pigment cholelithiasis pathogenesis by enhancing the biliary concentrations of this form of pigment.

Adult↗

Effect of skin pigmentation on the response to intradermal histamine.

The effects of injecting histamine phosphate, in serial 10-fold dilutions ranging from 0.0001 to 0.1 mg/ml histamine base, intradermally into three groups of nonatopic healthy volunteers with varying degrees of skin pigmentation were studied. The wheal sizes in the 30 Negroid subjects with darkly pigmented skins were consistently greater than those in both the 30 Caucasian subjects with light skin pigmentation and the 15 mixed Caucasian/Negroid subjects with light brown skins. The overall wheal response was the smallest in the Caucasian subjects. The differences in wheal sizes were greatest between the Negroid and Caucasian subjects for all dilutions, and these differences were statistically significant (p less than 0.005). From this study it appears that skin pigmentation has a profound effect on the wheal response to intradermally injected histamine. It is speculated that this difference in response may be related to the melanin pigment in the skin.

Black People↗

[Electron microscopic observations on the structure of the pigment epithelium in the region of the ora serrata].

The structure of the pigment epithelium at the ora serrata is examined in 10 human eyes aged from 31 to 90 years. The cells of the pigment epithelium show a different construction depending on their position relative to the ora. Directly at the ora serrata, in the cohesion band, the cells are higher and contain more pigment granula than those which are situated in a central region. In this sector we sometimes find overlapping of cells, which feigns two layers of epithelium. There are clearly fewer basal folding ins of the pigment epithelial cells at the oral than in the other parts of the retina. At the ora serrata pathological changes start in the 3rd decade of life. They include swelling and later on more or less pronounced cystoid degeneration of the epithelial cells. Within Bruch's membrane two kinds of cells are seen. In the ora gap six types of free cells can be distinguished, whose origin is discussed especially. Probably they originate from the chorioidea, the pigment epithelium and the sensory retina.

Adult↗

Pigment deposition in the anterior segment caused by melanocytoma of the optic disc.

A 34-year-old Japanese woman had a melanocytoma of the optic disc with scattered pigment particles in the vitreous in the left eye in 1970. Fifteen years later, we noticed pigment dispersion on the posterior lens surface, iris root, and trabecular meshwork, which resembled findings often caused by ocular malignant melanoma. Because the melanocytoma of the optic disc had decreased in size and the number of dispersed pigment particles in the vitreous cavity was reduced, it appeared that the pigmented particles produced by partial necrosis of the melanocytoma had resulted in the pigmentation of the anterior segment.

Adult↗

Sigma receptor antagonists inhibit human lens cell growth and induce pigmentation.

PURPOSE: The expression of the Sigma 1 receptor and the ability of receptor antagonists to inhibit growth and induce pigment formation were investigated in human lens epithelial cells. METHODS: Capsular bags were formed for experimental purposes by performing sham cataract operations on donor lenses. The resultant bags were cultured in Eagle's minimum essential medium (EMEM) alone or supplemented with the Sigma receptor antagonists rimcazole (3 microM) and BD1047 (10 microM). Cell growth was monitored by phase microscopy. Tyrosine incorporation was quantified by culturing in the presence of 14-C tyrosine for 24 hours. At the end of the culture period, some bags were fixed in 4% paraformaldehyde for electron microscopy, and others were plunged into liquid nitrogen for later immunoblot and PCR analyses. Protein levels of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2) were quantified by Western blot analysis. The presence of pigment granules within epithelial cells were monitored by phase and electron microscopy techniques. RESULTS: The Sigma-1 receptor was expressed in native human lens cells and in cultured capsular bag cells. The Sigma receptor antagonists BD1047 and rimcazole inhibited lens cell growth and, surprisingly, lens cells accumulated pigment granules in the presence of the antagonists. The antagonists raised preexisting levels of TYR and TYRP1, whereas there was no change in TYRP2. CONCLUSIONS: The human lens normally expresses components of the melanin synthesis pathway, and this suggests a possible origin for the pigment granules that have been observed under certain conditions in the human lens. Exposure of lens cells to Sigma receptor antagonists leads to growth inhibition and pigment granule production.

Blotting, Western↗

Absorption of bile pigments by the gall bladder.

A technique is described for preparation in the guinea pig of an in situ, isolated, vascularized gall bladder that exhibits normal absorptive functions. Absorption of labeled bile pigments from the gall bladder was determined by the subsequent excretion of radioactivity in hepatic bile. Over a wide range of concentrations, unconjugated bilirubin-(14)C was well absorbed, whereas transfer of conjugated bilirubin proceeded slowly. Mesobilirubinogen-(3)H was absorbed poorly from whole bile, but was absorbed as rapidly as unconjugated bilirubin from a solution of pure conjugated bile salt. Bilirubin absorption was not impaired by iodoacetamide, 1.5 mM, or dinitrophenol, 1.0 mM, even though water transport was affected. This indicated that absorption of bilirubin was not dependent upon water transport, nor upon energy-dependent processes. The linear relationship between absorption and concentration of pigment at low concentrations in bile salt solutions suggested that pigment was transferred by passive diffusion. At higher pigment concentrations or in whole bile, this simple relationship was modified by interactions of pigment with bile salts and other constituents of bile. These interactions did not necessarily involve binding of bilirubin in micelles. The slow absorption of the more polar conjugates and photo-oxidative derivatives of bilirubin suggested that bilirubin was absorbed principally by nonionic, and partially, by ionic diffusion. Concentrations of pure conjugated bile salts above 3.5 mM were found to be injurious to the gall bladder mucosa. This mucosal injury did not affect the kinetics of bilirubin absorption. During in vitro incubation of bile at 37 degrees C, decay of bilirubin and hydrolysis of the conjugate proceeded as first-order reactions. The effects of these processes on the kinetics of bilirubin absorption, and their possible role in the formation of "white bile" and in the demonstrated appearance of unconjugated bilirubin in hepatic bile, are discussed.

Absorption↗

Characterization of iris pigment epithelial cell for auto cell transplantation.

To establish auto iris pigment epithelial (IPE) transplantation, we characterized the properties of IPE cells and the method of culture using auto serum. Monkey and human IPE cells were obtained and cultured in several conditions, using auto, mouse, rabbit, bovine, or human serum. Immunocytochemical study was performed to confirm that the cells were epithelial in origin. The proliferation rate of the IPE was also calculated from fresh human IPE cells, which were obtained during filtering glaucoma surgery. Proliferation rate was also compared to that of retinal pigment epithelial (RPE) cells. Reverse-transcriptase and polymerase chain reaction for melanogenesis was performed, and the amount of pigment in the IPE cells was also calculated. Mouse and rabbit sera were not effective for the monkey IPE cell culture. Conversely, the cells grew well in the medium with auto, bovine, or human serum. Human IPE cells grew exponentially by the described methods and reached to 60,000 cells after about 4-5 weeks. When we compared them by proliferation rate, IPE cells were less proliferative than RPE cells. The gene expression for melanogenesis and the amount of pigment in the IPE gradually decreased through successive passages. Transplantation has been tried for the treatment of age-related macular degeneration using RPE from fetus or from eye bank eyes. However, focal rejection may play an important role in the clinical results. The establishment of auto IPE cell transplantation may improve the problem of rejection. In the present study, we established auto IPE cell culture using auto serum. The cultured IPE cell showed pigment epithelial cell properties until around five passages in both human and monkey.

Animals↗

Minocycline-induced cutaneous pigmentation.

BACKGROUND: Minocycline-induced cutaneous pigmentation is an adverse effect that may be more common than is generally realized. It is usually reported in patients undergoing chronic minocycline therapy for acne vulgaris. OBJECTIVE: The case of a 69-year-old woman taking minocycline for rheumatoid arthritis is presented, and its differential diagnosis discussed in order to characterize the clinical features of minocycline-induced cutaneous pigmentation. CONCLUSION: Patients undergoing minocycline therapy for rheumatoid arthritis may develop bluish-grey pigmentation over the legs and forearms. Cutaneous pigmentation is a well recognized adverse effect of minocycline therapy that is usually reported in young patients on chronic therapy for acne vulgaris. However, the antiinflammatory properties of minocycline have also made it useful in the management of various inflammatory conditions such as rheumatoid arthritis.1 We report the case of a 69-year-old woman who developed progressive cutaneous pigmentation, affecting mainly the legs, approximately 3 months after beginning minocycline therapy for rheumatoid arthritis.

Aged↗

The prognostic significance of residual pigmentation following radiotherapy of epidemic Kaposi's sarcoma.

The response to radiotherapy of epidemic Kaposi's sarcoma (EKS) is unusual in that irradiated regions are frequently left with a persistent purple stain, reminiscent of the color of the original tumor, but with no tumor mass. To date there are no published data to indicate whether the persistence of pigmentation can be predicted beforehand or if it has any prognostic import. We reviewed the response to treatment of 118 EKS lesions that were irradiated at New York University (NYU) Medical Center between 1981 and 1986. A total of 86 responded to treatment by complete clearance of the mass. Of these, 29 left residual purple pigmentation within the treatment portal, while 57 did not. Complete response (CR; without residual pigmentation) occurred more often in patients who had higher Karnofsky scores at the time of treatment. However, in terms of ultimate local control or survival, there were no differences between patients whose lesions cleared completely v those in whom pigmentation remained. We conclude that persistent pigmentation represents only a benign remnant of irradiated EKS and has no prognostic import.

Acquired Immunodeficiency Syndrome↗