bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pathogenesis of lipodermatosclerosis: facts, uncertainties and theories
Authors: Naschilz Jochanan E. , Yeshurun Daniel , Misselevich Ines , Boss Jochanan H. 
Published: July 2006

AbstractLipodermatosclerosis is the accepted term for describing induration of the skin and subcutaneous layers of the legs in patients with venous insufficiency. The pathogenic processes leading from venous insufficiency to lipodermatosclerosis are poorly understood. Based on their clinico‐pathological studies of different subcutaneous indurative disorders, the authors suggest that lipodermatosclerosis exhibits similarities to eosinophilic fasciitis and other fasciitis panniculus syndromes. The theories of the pathogenesis of lipodermatosclerosis are reviewed and a unifying pathogenetic concept is proposed. The lipodermatosclerosis is best conceived as fasciitis paniculata reaction evolving in the calf of the patient with venous insufficiency.
Multiple painful leiomyomas of the skin: a novel therapy with sympathicolysis?
Authors: Hauschild Axel , Maier Christoph , Christophers Enno 
Published: July 2006

AbstractLeiomyomatosis cutis is a rare disease involving large areas of the body surface with painful leiomyomas. Only a small panel of drugs has provided limited effects in the management of paroxysmal pain attacks associated with these tumours. Two patients with multiple, otherwise therapy‐refractors cutaneous leiomyomas predominantly on the extremities underwert experimental transient sympathicolysis. Experimental cold exposure and noradrenulin injections resulted in increasing pain and vasoconstriction. whereas sympathicolysis counteracted this with pain reduction and vasodilatation. Our results confirm that α‐adrenergic fibres play an important role in smooth muscle contraction and pain induction in cutaneous leiomyomas. Sympathicolysis should be induced in the therapeutic choices available for multiple painful leiomyomas localized on the extremities.
Efficacy of hydroxyurea in the treatment of a patient with erythrodermic psoriasis and chronic myelogenous leukaemia
Authors: Taveira Luis Miguel , Gonçalves Cristina , Paiva António , Selores Manuela , Sanches Madalena , Massa António 
Published: July 2006

AbstractA patient presenting with erythrodermal symptoms was diagnosed as having psoriatic erythroderma and chronic myeloid leukaemia. Both pathological conditions were effectively controlled with hydroxyurea within 9 months after diagnosis, without occurrence of adverse reactions or intolerance to therapy.
Trauma and Recovery: The Aftermath of Violence — from Domestic Abuse to Political Terror
Authors: Corcoran Carole Barody 
Published: July 2006

Trauma and Recovery: The Aftermath of Violence — from Domestic Abuse to Political Terror, Judith Lewis Herman. New York: Basic Books, 1992. 276 pp. $27.00. ISBN 0-465-08765–5. Shattered Assumptions: Toward A New Psychology of Trauma, Ronnie Janoff-Bulman. New York: The Free Press, 1992, 256 pp. $24.95. ISBN 0-02-916015–4.
Biosynthesis and Function of Melanins in Hepatic Pigmentary System
Authors: SICHEL GIOVANNI 
Published: July 2006

In this report we show the most important results obtained from our study of the pigment liver cells of Amphibia and Reptilia.Contrary to the cutaneous pigment cells that derive from the neural crest, the liver pigment cells, instead, derive from the Kupffer cells: this can be seen from the results obtained from labelled precursor incorporation experiments, not only in vivo but also in vitro, using surviving liver slices or isolated melanosomes.Chemical analysis of both liver and cutaneous melanosomes reveal a great difference in their chemical composition, and this is in agreement with the different origins of these cells.We therefore propose that: liver pigment cells of Amphibia and Reptilia should be classified as “Extra Cutaneous Pigment Cells from Histocytic Origin”.As regards the function of melanins, we show that O2 is trapped by these substances.Moreover, in my laboratory we have shown in several animal species, that the super‐oxide dismutase activity is inversely proportional to the quantity of melanin present; thus, we think that melanin could mime SOD activity.
Neutron Capture Therapy Research in Australia
Authors: ALLEN BARRY J. 
Published: July 2006

Neutron capture therapy research in Australia has continued to grow since the first Australia—Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry—an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines.Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious.Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters.A new approach to NCT utilises the enormous cross section of 157Gd and the induced‐Auger effect which has been shown to cause double strand breaks in circular DNA.
Boronated Monoclonal Antibody 225.28S for Potential Use in Neutron Capture Therapy of Malignant Melanoma
Authors: TAMAT SWASONO R. , MOORE DOUGLAS E. , PATWARDHAN ADITI , HERSEY PETER 
Published: July 2006

The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoconal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity.The present report describes the conjugation of dicesium‐mercapto‐undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma‐associated antigens (HMW‐MAA), using poly‐L‐ornithine as a “bridge” to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron‐monoclonal antibody conjugates has been studied by gel electrophoresis and ion‐exchange HPLC.
After Dopachrome?
Authors: PAWELEK JOHN M. 
Published: July 2006

Dopachrome, an intermediate in melanin biosynthesis, exhibits some unusual properties. At physiologic pH (e.g., pH 6‐8) it is unstable and spontaneously loses its carboxyl group to form 5,6‐dihydroxyindole (DHI(and CO2. However, over this same pH range, if various metals or a melanocyte‐specific enzyme are present, it rapidly rearranges to its isomer form—5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA)—which is far more stable than dopachrome in its ability to retain the carboxyl group. Whether or not the carboxyl group is retained could have important implications for the regulation of melanogenesis, since in the presence of oxygen DHI spontaneously forms a black precipitate, whereas DHICA forms a golden‐brown solution. The solubility of “DHICA‐melanin” is due to the presence of carboxyl groups, which provide negative charges and hydrophilicity. Thus, in vivo, the extent to which dopachrome is converted to DHI or DHICA may well influence the solubility and color of the melanin formed. The purpose of this article is to review recent findings in these areas and to discuss the possible significance of dopachrome conversion in the regulation of melanogenesis and color formation.SUMMARYThis review has explored events in the melanogenic pathway that are under regulatory control after the formation of dopachrome. No attempt was made to include the regulation of pheomelanin synthesis, although the same basic questions should exist for both pheo‐ and eumelanogenesis. It seems clear that the earlier concepts of melanogenesis, wherein tyrosinase was the only regulatory enzyme, are incorrect, at least for mammals. Elucidating the newly described pathways will take considerable research effort and ingenuity over the coming years.
Pigmentary System of the Adult Alpine Salamander Salamandra atra atra (Laur., 1768)
Authors: TREVISAN PIERLUIGI , PEDERZOLI AURORA , BAROZZI GIANCARLO 
Published: July 2006

The pigmentary system of the skin from adult specimens of the black alpine salamander Salamandra atra atra was investigated by light microscope, electron microscope, and biochemical studies. Results were compared with those obtained in previous study of the subspecies Salamandra atra aurorae. Unlike Salamandra atra aurorae, which presents epidermal xanthophores and iridophores, Salamandra atra atra is completely melanized, presenting only epidermal and dermal melanophores. The melanosomes in both the epidermis and the dermis appear to derive from a multivesicular premelanosome similar to that in the goldfish, and the epidermal melanosomes are smaller than those in the dermis. Premelanosomes with an internal lamellar matrix were not observed.The biochemical results have shown that in the ethanol extracts obtained from the skin in toto and from the melanosomes, pteridines and flavins are always present and are the same as those extracted from the black skin areas of Salamandra atra aurorae.
Materia Melanica: Further Dark Thoughts
Authors: RILEY P.A. 
Published: July 2006

The view is advanced that melanogenesis arose evolutionarily as a detoxification pathway for intrinsically‐generated orthoquinones.The primary impetus for the production of orthoquinones may have been their general antibiotic properties and the utility of these chemical species in forming covalent crosslinks between proteins, as illustrated by cuticular sclerotization in insects. It is argued that polymerization to give rise to visible pigments may have originated as a pathway for the inactivation of orthoquinones. The possible evolutionary advantages accruing from the generation of melanin are discussed with special reference to acuity of photoreceptors and the physico‐chemical properties of melanin, as well as the contribution of melanin to protective colouration or display.
Melanin Biosynthesis From Dopamine. II. A Mass Spectrometric and Collisional Spectroscopic Investigation
Authors: COSTA CARLO , BERTAZZO ANTONELLA , ALLEGRI GRAZIELLA , TOFFANO GINO , CURCURUTO ORNELLA , TRALDI PIETRO 
Published: July 2006

Electron impact (EI) and fast atom bombardment (FAB) mass spectrometry together with collisional activation (CA) experiments were applied to the study of the oxidation pathway of dopamine by tyrosinase. In order to prevent attachment of the protein to the highly reactive intermediates, ultrafiltration was employed to remove the enzyme at different reaction times. FAB, privileging molecular species formation, was successfully used for identification of transient intermediates and their relative concentrations with respect to time, directly in the reaction mixture. The presence of isobaric molecular species made chromatographic separation necessary. Further EI mass spectrometry and collision spectroscopy led to structural identification of pure components. Of these, dopamine‐o‐quinone, leucoaminochrome, and aminochrome semiquinone were characterized for the first time as real intermediates in dopamine melanogenesis, in agreement with previous hypotheses.This approach elucidated the pathway of dopamine melanogenesis.
Vitiligo: Where Do We Stand?
Authors: ORTONNE JEAN‐PAUL , BOSE SUMIT KUMAR 
Published: July 2006

Vitiligo is a puzzling disorder characterized by a disappearance of epidermal and/or follicular melanocytes by unknown mechanisms. This very common disorder involving 1–4% of the world population is thus of great importance for the practicing dermatologist. The cellular and molecular mechanisms leading to the destruction of melanocytes in this disorder have not yet been elucidated, making it of major interest for the cell biologist involved in melanocyte research.Recent advances in this field, due largely to the availability of techniques for culturing normal human melanocytes, opened new perspectives in the understanding of vitiligo. Although vitiligo has long been considered a disorder confined to the skin, there is now good evidence that it also involves the extracutaneous compartment of the “melanocyte organ.” It is also clear that vitiligo is not only a melanocyte disorder, but that it also involves cells, such as keratinocytes and Langerhans cells, found in the epidermis and follicular epithelium.The three prevailing theories of the pathogenesis of vitiligo are the immune hypothesis, the neural hypothesis, and the self‐destruct hypothesis. New hypotheses suggest that vitiligo may be due to (1) a deficiency in an unidentified melanocyte growth factor, (2) an intrinsic defect of the structure and function of the rough endoplasmic reticulum in vitiligo melanocytes, (3) abnormalities in a putative melatonin receptor on melanocytes and (4) a breakdown in free radical defense in the epidermis. None of these hypotheses has been demonstrated, and according to the available data, it is likely that the loss of epidermal and follicular melanocytes in vitiligo may be the result of several different pathogenetic mechanisms.
Atypical Granules in the Eyes of the White Mutant of Drosophila melanogaster Are Lysosome‐Related Organelles
Authors: SCHRAERMEYER ULRICH , DOHMS MARIANNE 
Published: July 2006

In the pigment cells of the white mutant of Drosophila melanogaster, as described earlier, two types of abnormal granules are found by conventional electron microscopy. However, both types of abnormal granules, in addition to those in pigment cell invaginations, are also present in the cytoplasm of the photoreceptor cells.Three enzymes (acid phosphatase, peroxidase, and tyrosinase) are localized within the eyes of wild type and white mutant Drosophila melanogaster by electron microscopy. Peroxidase activity is present in lamellar bodies close to the rhabdomeral microvilli of both fly types. However the organelles containing peroxidase activity are 6‐fold more frequent in the wild type than in the mutant. Acid phosphatase is present in lamellar bodies between and at the bases of the rhabdomeral microvilli of the wild type, as well as in ommochrome granules of the photoreceptor cells. In the white mutant, however, acid phosphatase was located in electron lucent vacuoles in the cytoplasm of the receptor cells. These acid phosphatase‐positive vacuoles also contained both types of abnormal granules. The latter result indicates that abnormal granules in the receptor cells originate from lysosomal degradation and that targeting of lysosomal enzymes is altered in the white mutant.Due to the tyrosinase activity in the hemolymph of flies, the extracellular spaces are electron dense after DOPA incubation. Since some abnormal granules within the photoreceptor cells are not surrounded by an extracellular space, they can be assumed to originate within the photoreceptor cells.
Application of Photoacoustic Phase Angle Spectroscopy (φAS) to Eumelanins and Pheomelanins
Authors: CAITI ELENA , CRIPPA PIER RAIMONDO , VIAPPIANI CRISTIANO 
Published: July 2006

A new technique, based on the measurement of the phase angle of the photoacoustic signal, was used for investigating the absorption spectra of melanins in the dry state. The main advantages of such a method are the insensitivity to scattering of the light and the applicability to nontransparent or highly adsorbing and thermally thick samples. The spectra obtained on different kinds of natural and synthetic melanins show much more details than the corresponding ones obtained spectrophotometrically on aqueous suspensions of the pigment.Some relevant features of the spectra still cannot be interpreted, yet we were able to show the presence in eumelanins of dopachrome at 475 nm and melanochrome at 540 nm, and in pheomelanins of compounds previously isolated from red chicken feathers. Moreover, the well known trend of the optical absorption, i.e., its decrease with increasing wavelength, was unambiguously confirmed.
Characterization of Melanogenesis in Normal Human Epidermal Melanocytes by Chemical and Ultrastructural Analysis
Authors: NAKAGAWA HIDEMI , IMOKAWA GENJI 
Published: July 2006

Chemical and ultrastructural studies were conducted to define the relationship between type of melanogenesis and fine structures of melanosomes in normal human epidermal melanocytes. Chemical analysis of epidermal melanin demonstrated that the ratio of eumelanin/pheomelanin varied individually, ranging from 1.31 to exclusively eumelanic. Ultrastructural analysis of fine structures of melanosomes revealed that spheroid melanosomes were frequently observed in melanocytes of the epidermis whose eumelanin/pheomelanin ratio was less than 5. Conversely, ellipsoid melanosomes predominated in melanocytes of the epidermis whose ratio was more than 10.On the basis of these findings, it seems reasonable to conclude that 1) normal human epidermal melanocytes synthesize both eumelanin and pheomelanin and 2) pheomelanin synthesis may be characterized by the presence of spheroid melanosomes whereas eumelanin synthesis is ascribed to ellipsoid melanosomes.
Human Epidermal Melanocyte and Keratinocyte Melanocortin Receptors: Visualization by Melanotropic Peptide Conjugated Microspheres (Latex Beads)
Authors: JIANG JINWEN , SHARMA SHUBH D. , HRUBY VICTOR J. , BENTLEY DAVID L. , FINK JODY L. , HADLEY MAC E. 
Published: July 2006

The objectives of this research were to determine whether melanocortin receptors are characteristic (constant) membrane markers of human epidermal melanocytes. Methodologies were developed to visualize melanotropin receptors by scanning electron microscopy (SEM). Multiple copies (up to a hundred) of [Nle4,D‐Phe7]α‐MSH, a superpotent analog of α‐melanocyte stimulating hormone (α‐MSH), were conjugated to a macromo‐lecular carrier (latex beads: microspheres). Incubation in the presence of the melanotropin‐conjugated microspheres resulted in binding of human normal epidermal melanocytes to the beads. Almost every (possibly all) melanocyte possesses melanocortin receptors as visualized by SEM.Specificity of binding of the macromolecular conjugate was demonstrated by several studies: 1) Binding of melanocytes to the microspheres was specific since it could be blocked by prior incubation of the cells in the presence of the unconjugated hormone analog; 2) microspheres lacking bound ligand did not bind to the melanocytes; 3) micro‐spheres that were first treated with reducing agents (e.g., dithiothreitol) did not subsequently bind to melanocytes; 4) another peptide hormone ligand (e.g., a substance‐P analog) attached to the latex beads failed to bind to the cells; 5) B16/F10 mouse melanoma cells known to express melanocortin receptors bound to the microspheres; and 6) cells of nonmelanocyte origin (e.g., mammary cancer cells, small‐cell lung cancer cells, fibroblasts) did not bind to the macromolecular conjugate. One exception was that human epidermal keratinocytes also expressed melanocortin receptors as determined by all the criteria established above for epidermal melanocytes. Thus, cell specific melanocortin receptors appear to be characteristic cell surface markers of epidermal melanocytes and keratinocytes.
Evidence to Suggest That Expression of MITF Induces Melanocyte Differentiation and Haploinsufficiency of MITF Causes Waardenburg Syndrome Type 2A
Authors: TACHIBANA MASAYOSHI 
Published: July 2006

MITF (microphthalmia‐associated transcription factor) encodes a transcription factor with a basic‐helix‐loop‐helix‐leucine zipper (bHLH‐Zip) motif. Ectopic expression of MITF is found to convert NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci, which superficially resembled those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase‐related protein 1. Such properties were not observed in cells transfected with the closely related gene, TFE3. These findings indicated that MITF is involved in melanocyte differentiation.Two mutations (C760.T and C895.T) in MITF are found to be associated with individuals with Waardenburg syndrome type 2 (WS2). These mutations create stop codons in exon 7 and 8, respectively, and probably result in truncated proteins lacking HLH‐Zip or Zip structure. To understand how these MITF mutations cause WS2 in heterozygotes, mutant MITF proteins were generated and used for DNA‐binding and luciferase reporter assays. The mutated MITF proteins lose their DNA‐binding activity and fail to transactivate the promoter of the tyrosinase gene. However, these mutated proteins do not appear to interfere with the activity of wild‐type MITF protein in these assays, indicating that they do not show a dominant‐negative effect. These findings suggest that the phenotypes of the two WS2 families are caused by loss‐of‐function mutations in one of the two MITF alleles, resulting in haploinsufficiency of the MITF protein, the transcription factor necessary for normal melanocyte differentiation.
Application of the New Stereological Probes to the Study of the Melanosome in Cloudman S91 Melanoma Cells
Authors: FANG DONG , DOCKERY PETER , WEATHERHEAD BRIAN 
Published: July 2006

The relationship between melanosome size and number and melanin content has been investigated in Cloudman S91 melanoma cells growing in vitro using both “model‐based” and “design‐based” stereological procedures. Cells were cultured for 4 days, harvested at daily intervals, and resin‐embedded for light and electron microscopy; one aliquot of each sample of cells was assayed to determine its melanin content.By comparing their volume‐weighted mean nuclear volume and their number‐weighted mean nuclear volume, we have found that the nuclei of Cloudman melanoma cells form a fairly homogeneous population. The volume fraction and absolute volume of premelanosomes (Vvpm, cell and Vpm) and mature melanosomes (Vvmm, cell and Vmm) were all found to decrease progressively throughout the period of culture as did the number of premelanosomes (Npm) and mature melanosomes (Nmm). Whilst the volume‐weighted mean volume of individual stage I and stage II premelanosomes, (vipm), remained fairly constant at about 10 nm3, the volume of individual stage III and IV mature melanosomes showed significant variation ranging between about 13 nm3 and 32 nm3. The melanin content of the cells decreased progressively over the 4 days of culture. There were, however, considerable variations in both the average melanin content per unit volume of mature melanosomes, in the range 170–600 fg/μm3, and in the melanin content per individual mature melanosome, in the range 3–12 fg.Our findings show that stereological techniques can provide unbiased and sensitive tools for the study of the morphological basis of melanogenesis; their value will become even more evident when they are combined with techniques for the localization of melanogenic enzymes and their substrates.