bluuebunny/crossref_metadata_2025 huggingface dataset:
Definitional Research on African American Students and Sexual Harassment
Authors: Mecca Susan J. , Rubin Linda J.
Published: July 2006

A total of 100 African American undergraduate students were given the Sexual Experiences Questionnaire (SEQ) (Fitzgerald et al., 1988) and an open-ended question assessing experiences of sexual harassment. Results showed a significant frequency of sexual imposition (19%), particularly sexual touching. Participants also clearly delineated a new category of sexual harassment previously untapped by largely Caucasian studies: comments or sexual attention based solely on racial stereotypes or racially based physical features. In conclusion, the reported differences with regard to experiences and definitions of sexual harassment indicate that previous assumptions of homogeneity of experience (with Caucasian women being the standard) appear to be incorrect.
To Be Female, Middle Class, Anxious, and Black
Authors: Neal-Barnett Angela M. , Crowther Janis H.
Published: July 2006

Women of color theorists have suggested that the double minority status of gender and ethnicity places African American women at higher risk for anxiety. However, little information is available about anxiety disorders among African American women. The existing literature subsumes Black women under the general category of African Americans and focuses on low-income samples. In this study, we examine the manifestation of panic disorder in a sample of 15 predominantly middle-class African American women. We then compare these women to a group of 35 predominantly middle-class African American women without panic disorder on several factors, including presence of isolated sleep paralysis, presence of other anxiety disorders, help-seeking behavior, and victimization. Results indicate that African American women with panic disorder experienced isolated sleep paralysis, and that both groups had high levels of sexual victimization. Help-seeking among women with panic and other anxiety disorders was limited to relationship difficulties, sexual assault, and bereavement.
The Effect of Occupational Status Cues on Memory for Male and Female Targets
Authors: Stewart Tracie L. , Vassar Patricia M.
Published: July 2006

In an experiment examining the influence of status cues on memory, participants read trait descriptions and formed impressions of either four male or four female targets: two labeled as professors and two labeled as graduate students. They then attempted to recall which traits had described each target. Because pretests confirmed that professors were perceived as having higher status than graduate students, we predicted better recall for male professors than male graduate students. Pretesting also indicated that men were viewed as having higher status than women; consequently, we expected occupation cues to have less impact on the female target condition due to the lower status and possible lesser individuation of the female targets overall. As predicted, there were significantly fewer memory errors for male professors than for male graduate students; however, occupational status did not significantly affect memory for female targets.
Assessing Women's Feminist Identity Development: Studies of Convergent, Discriminant, and Structural Validity
Authors: Fischer Ann R. , Tokar David M , Mergl Marija M. , Good Glenn E. , Hill Melanie S. , Blum Sasha A.
Published: July 2006

Researchers have called for increasing sophistication in the assessment of women's feminist identity development (Enns & Hackett, 1990; Hackett, Enns, & Zetzer, 1992) to understand important psychological processes. This series of studies examined recent efforts to operationalize Downing and Roush's (1985) model of feminist identity development. Specifically, the psychometric properties of two existing measures—the Feminist Identity Development Scale (Bargad & Hyde, 1991) and the Feminist Identity Scale (Rickard, 1987)—were examined in two studies with separate samples of women (total N = 486). Results of Study 1 indicated the strengths and significant limitations associated with each scale (e.g., low internal consistency for some subscales, item-subscale inconsistency). A composite measure (derived from these scales) with better overall psychometric properties is described. In Study 2, we found good support for the composite instrument's internal consistency, as well as convergent, discriminant, and factorial validity in a sample that included a wide age range and nonstudent community residents.
The Gender Stereotyping of Emotions
Authors: Plant E. Ashby , Hyde Janet Shibley , Keltner Dacher , Devine Patricia G.
Published: July 2006

Three studies documented the gender stereotypes of emotions and the relationship between gender stereotypes and the interpretation of emotionally expressive behavior. Participants believed women experienced and expressed the majority of the 19 emotions studied (e.g., sadness, fear, sympathy) more often than men. Exceptions included anger and pride, which were thought to be experienced and expressed more often by men. In Study 2, participants interpreted photographs of adults' ambiguous anger/sadness facial expressions in a stereotype-consistent manner, such that women were rated as sadder and less angry than men. Even unambiguous anger poses by women were rated as a mixture of anger and sadness. Study 3 revealed that when expectant parents interpreted an infant's ambiguous anger/sadness expression presented on videotape only high-stereotyped men interpreted the expression in a stereotype-consistent manner. Discussion focuses on the role of gender stereotypes in adults' interpretations of emotional expressions and the implications for social relations and the socialization of emotion.
Anger and Depression in Girls and Boys: A Study of Gender Differences
Authors: Cox Deborah L. , Stabb Sally D. , Hulgus Joseph F.
Published: July 2006

A growing body of literature supports the link between anger suppression and depression and females' greater likelihood than males of demonstrating both. Anger suppression was hypothesized to be involved in the development of gendered identity for girls, specifically by rendering girls more likely to experience depression. Employing an ethnically diverse sample of public school children, differences between fifth through ninth grade girls and boys in anger suppression and depression were investigated using self-report data. Results supported the hypothesis that girls suppress anger at higher rates than boys but not the related hypothesis that this suppression results in higher levels of depression. Age was not related to either anger suppression or depression, and no significant relationship was found between suppressed anger and depression for either sex. The impact of girls' anger suppression on their emotional and gender development is discussed.
Ability of Melanins to Protect Against the Radiolysis of Thymine and Thymidine
Authors: HILL HELENE Z. , HUSELTON CHRISTINE , PILAS BARBARA , HILL GEORGE J.
Published: July 2006

Individuals with black skin rarely get skin cancer, and melanomas, tumors arising from pigmented cells, are generally resistant to radiation therapy. The role of melanin in these two phenomena has not been defined, but oxygen‐radical species have been implicated in both effects. These studies were undertaken to determine the ability of various melanins to compete for ionizing radiation‐produced radicals which destroy nucleic acid bases. The ability of Sigma eumelanin (S‐eumelanin) to protect against the radiolysis of thymidine in buffered solutions was compared to the protective ability of seven amino acids, including melanin precursors; bovine serum albumin, as a model protein; ficoll, as a model polysaccharide; and DNA. Both proteins and polysaccharides are known to scavenge hydroxyl radicals in cells. The concentration of thymidine after exposure to gamma radiation was determined by High Performance Liquid Chromatography (HPLC) analysis after removal of insoluble melanin by acid precipitation. S‐eumelanin was more effective at competing with thymidine for free radicals than bovine serum albumin, Ficoll, or DNA, but less effective than certain of the small molecules. Several of the above compounds were also examined for ability to protect against thymine radiolysis. In addition, melanins from other sources were compared to S‐eumelanin. Of these, enzymatically synthesized phaeomelanin was the most effective. The results indicate that melanins can compete for base‐ and nucleoside‐damaging free radicals more effectively than other cellular macromolecules. Of the small molecules, the phenolic compounds had the greatest scavenging ability. In vivo, melanins are found in melanosomes bound to protein. Therefore, the relevance of these findings to the photo‐ and radiobiology of melanins in vivo has yet to be determined.
Pteridines and Purines as Major Pigments of the Avian Iris
Authors: OLIPHANT LYNN W.
Published: July 2006

Stromal pigments from the irises of 28 species of birds having brightly colored eyes were extracted and analyzed. Carotenoids were present in six species and they were the sole bright pigment in only two of these. The iris pigments of the majority of the birds examined were soluble in 0.1 M NaOH and chromatographic analysis indicated they were primarily pteridines and purines. The pteridines often occurred in a crystalline state, either alone or, more commonly, in conjunction with purines.
Neuromelanin and its Possible Protective and Destructive Properties
Authors: LINDQUIST NILS GUNNAR , LARSSON BENGT S. , LYDÉN‐SOKOLOWSKI ANNIKA
Published: July 2006

The function of neuromelanin is not known, but some properties of the pigment suggest a protective action. Its unique ability to accumulate and retain several compounds, such as various amines and a number of metals, may protect the pigment‐containing neurons from high exposure to harmful substances. This possible mechanism of protection may however in certain instances be of a double‐edged nature, as accumulation of neurotoxic agents with a high melanin affinity may cause toxic concentrations in the neuro‐melanin‐containing cells. MPTP (l‐methyl‐4‐phenyl‐l,2,3,6‐tetrahydropyridine) seems to be such a compound, as it has been found to preferentially destroy neuromelanin‐containing cells. The degree of MPTP neurotoxicity seems to be related to the amount of neuromelanin present in the particular species. It is possible that also manganese, which is known to cause an extrapyramidal disorder resembling Parkinson's disease, causes injury to neuromelanin‐bearing neurons due to its melanin affinity. This mechanism may be involved in other forms of chemically induced Parkin‐sonism and possibly also in idiopathic Parkinson's disease, although the offending agent remains to be discovered.
Divisionistic Generation of Skin Hue and the Change of Shade in the Scalycheek Damselfish, Pomacentrus lepidogenys
Authors: KASUKAWA HIROAKI , OSHIMA NORIKO
Published: July 2006

In addition to melanophores and xanthophores, there existed two types of iridophore in the dermis of the scalycheek damselfish, Pomacentrus lepidogenys. There are dendritic iridophores which reflect white light‐rays by Tyndall scattering, and the round or somewhat ellipsoidal iridophores which reflect rays with a relatively narrow spectral peak from blue to green through the non‐ideal thin‐film interference. Most of the dendritic iridophores were covered with xanthophores and were situated over melanophores, thus constituting a kind of chromatophore unit which produces a yellow or yellowish‐green color. The characteristic yellowish‐green hue of the integument results from a compound effect of small contributions by more elementary colors. During color changes of the skin, the position of the spectral peak does not shift. Unlike the iridophores of the blue damselfish, both types of iridophore of the scalycheek damselfish were found to be inactive. It appears, therefore, that the aggregation and dispersion of pigment within the melanophores is the primary mechanism responsible for the changes in color of this species.
Migration of Epidermal Melanophores to the Dermis Through the Basement Membrane During Metamorphosis in the Frog, Rana japonica
Authors: YASUTOMI MASUMI
Published: July 2006

The number of epidermal melanophores of the skin decreases dramatically during metamorphosis in the frog, Rana japonica. This decrease may represent an adaptation for rapid color change, a property which the animal acquires after metamorphosis. We concluded that the decrease was due to the migration of epidermal melanophores to the dermis. Epidermal melanophores and epidermal cells are tightly associated with each other in the young tadpole. The association becomes looser at the metamorphic stage and, occasionally, small breaks in the basement membrane are seen. These breaks may facilitate the migration. The migration was observed exclusively at the metamorphic stage, in spite of careful observation of other stages under the electron microscope. The migration of epidermal melanophores was induced by treatment with thyroxine of cultured skin from tadpoles at stage 15, and this hormone may act directly on epidermal melanophores.

Until now, the increase in the number of dermal melanophores during metamorphosis has been explained by the differentiation of dermal melanophores from melanoblasts and by their mitotic division. Our results show that the migration of epidermal melanophores to the dermis may be a factor which accounts for the increase in the number of dermal melanophores.
Melanophore Differentiation in the Periodic Albino Mutant of Xenopus laevis
Authors: FUKUZAWA TOSHIHIKO , IDE HIROYUKI
Published: July 2006

That embryonic ventral truck tissue might play a role in expression of the periodic albino mutant phenotype (ap/ap) in Xenopus laevis was suggested from the experiments of MacMillan (1980). In contrast, the present experiments, involving the culture of isolated regions of Xenopus embryos, have demonstrated that both mutant and wild‐type melanoblasts differentiate independently of a ventral trunk factor. A similar conclusion, that mutant melanoblasts differentiate independently of a ventral trunk factor, is derived from observations on neural crest cultures, wherein melanization of neural crest cells in both wild‐type and mutant cultures occurred in a manner consistent with their genotype.
Tyrosinase Protein Is Expressed Also in Some Neural Crest Derived Cells Which Are Not Melanocytes
Authors: HANINEC PAVEL , VACHTENHEIM JIRÍ
Published: July 2006

Some neural crest cells give rise to pigment cells in early ontogenesis. We tested here whether tyrosinase‐a key enzyme in melanogenesis—was present in some nonpigment neural crest derivatives in adult hamsters.

Interestingly enough, inactive tyrosinase protein was detected, using indirect immunofluorescence, in the satellite cells of spinal ganglia and Schwann cells of sciatic and facial nerves in normal adult animals. The results of cell blotting from spinal ganglia were similar to the fluorescence findings.

Thus, our results seem to support the hypothesis that Schwann cells, satellite cells of spinal ganglia, and melanocytes may be more intimately related developmentally than other neural‐crest‐derived cells. Moreover, since we detected tyrosinase protein in cells which normally do not produce melanosomes, it could be deduced that, during the melanocyte's differentiation from its cell precursor, the expression of tyrosinase protein might precede the point when melanosomes begin to differentiate from known cytoplasmic structures.
Exploring the Evolutionary History of Melanin‐Concentrating and Melanin‐Stimulating Hormone Receptors on Melanophores: Neopterygian (Holostean) and Chondrostean Fishes
Authors: SHERBROOKE WADE C. , HADLEY MAC E.
Published: July 2006

The occurrence of melanin‐concentrating hormone (MCH) receptors on integumental melanophores was found to extend back in the evolutionary line of ray‐finned bony fishes (Actinopterygii) to the group ancestral to modern teleosts, the Holostei. The two species of holosteans studied, Amia calva and Lepisosteus platyrhincus, exhibited changes of melanophore index (melanosome aggregation), indicating responses to MCH and to melatonin but no response to norepinephrine (NE). Polyodon spathula, a species of chondrostean (an older group of bony fishes ancestral to holosteans), failed to respond to MCH, to melatonin, or to NE. Nevertheless, Polyodon skin darkened (melanosome dispersion) in response to melanocyte‐stimulating hormone (MSH). The preliminary implication of these observations is that the mechanism of physiological color change involving MCH and its melanophore receptors evolved near the end of the Paleozoic or during the early Mesozoic, just before or early in the evolution of neopterygian (holostean and teleostean) fishes.
Melanocytic Carcinogenesis in Albino Guinea Pigs
Authors: GOMEZ SALVADOR , VICENTE VICENTE , OCHOTORENA Mα‐MAR , HERNANDEZ‐GIL ANTONIO
Published: July 2006

We describe an experimental model for the induction of cutaneous melanomas in albino guinea pigs by means of repeated topical application of 7, 12‐dimethyl‐benzan‐thracene over 13 consecutive months. At the end of the experiment 87.5% of the animals presented multiple lesions of a melanocytic nature. The most frequent and the earliest detected was melanocytic hyperplasia, followed by dysplasia. These lesions occurred in 75% of animals and were observed from the 4th month onward. Nevus‐type lesions appeared from the 12th month and affected 70% of animals, whilst melanomas occurred in 65%. Metastases were observed in 45% of animals, in lungs, lymph nodes, kidney, and adrenal gland.
Physiology and Pathophysiology of Inner Ear Melanin
Authors: GOTTESBERGE A.M. MEYER zum
Published: July 2006

The presence of melanin in the inner ear was established more than a century ago, but the exact biological function of the pigment in the labyrinth has yet to be deter‐mined. In this brief review, the correlation of pigmentation and inner ear function, as well as the presumed role of melanocytes in hereditary diseases are discussed. Special attention was drawn to the composition of melanin and its presumed function as a biological reservoir for divalent ions and as an ion exchanger, as well as an intracellular buffering system for calcium. It is pointed out that melanin is capable of binding ototoxic drugs. Finally, morphological responses of melanocytes to local disturbance of Ca++ homeostasis in the inner ear are described as 1) intracellular movement and intraepithelial deposition of melanosomes; 2) cell motility; 3) neomelanogenesis; and 4) enhanced exocytotoxic/endocytotic activity. The possible consequences of this malfunction of the melanocytes on the inner ear function are discussed.
The Regulatory Role of Sulfhydryl Compounds in Melanogenesis
Authors: PROTA GIUSEPPI'E , D'ISCHIA MARCO , NAPOLITANO ALESSANDRA
Published: July 2006

Since the discovery in 1967 of the phaeomelanin pathway the regulatory role of sulfhydryl compounds in epidermal melanin pigmentation has been a major focus in pigment cell research. The current state of knowledge in the field is briefly discussed, with special reference to some recent studies extending the possible targets of sulfhydryl compounds to pigment intermediates beyond the dopaquinone stage.
Enhanced Susceptibility of Melanocytes to Different Immunologic Effector Mechanisms In Vitro: Potential Mechanisms for Postinflammatory Hypopigmentation and Vitiligo
Authors: NORRIS D.A. , CAPIN L. , MUGLIA J.J. , OSBORNI R.L. , ZERBE G.O. , BYSTRYN J.C. , TONNESENI M.G.
Published: July 2006

In postinflammatory hypopigmentation and in vitiligo, one observes histologic evidence of melanocyte damage, disappearance of melanocytes, and clinical loss of pigmentation. In the case of vitiligo, this loss of pigment is complete. There is considerable evidence that melanocytes are highly susceptible to autocytotoxic damage and perhaps to specific immunologic damage. We directly compared the susceptibility of cultures of melanocytes (M), keratinocytes (K), endothelial cells (EC), and fibroblasts (F) to hydrogen peroxide damage across a Wide range of concentrations (10‐7‐10‐2 M) and analyzed the differences by computerized Probit analysis. Cytotoxicity was measured by three dye techniques: acridine orange/ethidium bromide (AO/EB), fluorescein diacetate (FD), and nigrosin (N). All three assays produced similar results. The order of susceptibility to H202 was M < EC < K < F. The LD50 of melanocyte targets was two orders of magnitude lower than that of fibroblasts. The AO/EB assay was used to study immunologic cytotoxicity of melanocytes in the presence of sera from vitiligo patients plus either complement or cellular effectors of antibody‐dependent cellular cytotoxicity (ADCC). Eleven vitiligo sera and 11 control sera were contrasted in 4‐ and 16‐hr cytotoxicity assays. Vitiligo patients' sera containing antimelanocyte antibodies induced both complement lysis and ADCC of melanocytes. Thus the melanocyte is highly susceptible to peroxide‐induced damage, complement lysis, and ADCC. In addition, antibodies in vitiligo sera appear to be an important trigger of melanocyte damage by complement and ADCC effectors and are likely to be involved in the melanocyte damage observed in vitiligo.
Genetic and Epidemiologic Evaluation of Dysplastic Nevi
Authors: MEYER LAURENCE J. , PIEPKORN MICHAEL W. , SEUCHTER SUSANNE A. , CANNON‐ALBRIGHT LISA A. , TIMOTHY BISHOP D. , ZONE JOHN J. , SKOLNICK MARK H.
Published: July 2006

Dysplastic Nevus Syndrome (DNS) has been defined as that trait characterized by the presence of at least one dysplastic melanocytic nevus. DNS was originally described in kindreds having multiple members with melanoma. Various types DNS have been described in other situations to include individuals with apparently sporadic cases, familial DNS without melanoma and individuals with apparently sporadic DNS with melanoma. These categories are based on historical information in general, and not on examination of family members. In all cases, the presence of dysplastic nevi appear to confer some increased risk of melanoma, which varies between the groups. Similarly cutaneous melanoma is thought to occur in several distinct populations‐random individuals without DNS, individuals with sporadic DNS, and those with familial DNS.

Genetic analysis of DNS has been largely confined to the classically ascertained kindreds associated with melanoma. These studies have usually used diagnostic criteria based on pathology of clinically selected material, and that evidence suggests that DNS is inherited as an autosomal dominant trait in these families. Surveys of the general population have detected rates of dysplastic nevi of 5% 20%. In our Utah‐based studies, we have evaluated probands and family members from three groups. These included kindreds with multiple occurrences of melanoma, random individuals with at least one dysplastic nevus, and cases of melanoma with unknown family history. Controls were spouses of study subjects. We sought to determine the percentage of each group associated with dysplastic nevi and/or genetic DNS. The range of phenotype of patients with dysplastic nevi was large with some individuals having few nevi, none of which were clinically atypical, and others having greater than 100 nevi. The prevalence of dysplastic nevi in at least one of two biopsies in Utah population controls is presently Wtimated at 62%. Some probands with melanoma as well as some of their relatives had elevated numbers of nevi, suggesting that this predisposition to melanoma may be inherited.
Dysplastic Nevus Syndrome in The Netherlands
Authors: BERGMAN WILMA , VAN HAERINGEN ARIE
Published: July 2006

In Europe, the occurrence of familial melanoma in combination with the occurrence of dysplastic nevi in melanoma patients has been reported by groups from Scotland, France, Italy, and The Netherlands. The major publications of these groups are briefly mentioned and summarized. This report specifically describes nine extensive Dutch pedigrees. Clinical an genetic studies were performed in kindreds among whom three or more individuals with melanoma occurred in at least two consecutive generations. Three hundred sixty‐two living persons older than 10 years were screened. The mean number of family members was 60, which makes these pedigrees preeminently suited for genetic studies. Spouses were not included in the study. One hundred eighty individuals were recognized as gene carriers. After correction for bias of ascertainment, we calculated a segregation rate of 0.45, compatible with dominant inheritance. Of the 180 living or alive at the start of the study, 40 had a melanoma, 118 had dysplastic nevi, and 22 were regarded as obligate gene carriers on the basis of their position in the pedigree. The finding of nonpenetrance and reduced penetrance of the characteristic phenotype of the dysplastic nevus syndrome has important consequences for daily practice. When a family is requested to attend the pigmented lesion clinic, all members have an a priori risk of 50% of carrying the gene. Individuals without any abnormalities form the majority, and cases of nonpenetrance and low penetrance are mixed in with the seemingly normal cases. The consequence for our research group was to follow all family members until it is possible to distinguish definitely gene carriers from normal family members. Other malignancies occurred at an increased rate among these families. In two families, the occurrence of several kinds of cancer was obvious. Twenty‐four instances of nonmelanoma cancer were found, among which were seven cases of pancreatic carcinoma
Comparison of 5′‐Nucleotidase Activities Among Cultured Murine Melanoma Cell Lines
Authors: MOODY DANA , WILLIAMS LAURA J. , GERSTEN DOUGLAS M.
Published: July 2006

The activity of 5′‐nucleotidase and ouabain‐sensitive Na/K ATPase was determined in seven different mouse melanoma cell lines. Ouabain‐sensitive Na/K ATPase activity was found in NP40‐treated cell homogenates of all cell lines. However, 5′‐nucleotidase activity was found in only one mouse melanoma cell line—JB/RH. The absence of expression of 5′‐nucleotidase activity in the other six cell lines is not associated with pigmentation in melanoma cells, nor is the gene switched off in all transformed melanocytes of C57BL/6 origin.
Citrate Activates Tyrosinase From B‐16 Murine Melanoma and Human Skin
Authors: CHAYA DEVI CHINTAMANENI , TRIPATHI RAM KUMAR , RAMAIAI ABBURI
Published: July 2006

Citrate stimulates cresolase activity of tyrosinase from B‐16 murine melanoma and human skin. Maximal stimulation by citrate was obtained at 2 mM, and stimulation was decreased at higher concentrations. Citrate stimulates tyrosinase not only from mammalian sources but also from mushroom. The stimulation was not due to reversal of inhibition of enzyme activity by excess tyrosine. On rapid decrease in pH of the enzyme solution from 6.8 to 5.0–5.2, the enzyme is no longer inhibited by excess tyrosine even when its activity was assayed at pH 6.8. Citrate also stimulates this form of enzyme. However, the stimulation is more at acidic pH than at pH 6.8. At higher concentrations of citrate the stimulatory effect decreases at both pH 5.0 and pH 6.8. Inhibition of this enzyme occurs at higher concentrations (22 mM) at pH 6.8. The physiological role of stimulation of cresolase activity of tyrosinase by citrate is yet to be unravelled.
Investigation of the Regulation of Pigmentation in α‐Melanocyte‐Stimulating Hormone Responsive and Unresponsive Cultured B16 Melanoma Cells
Authors: HILL SARAH E. , BUFFEY JAYNE , THODY ANTHONY J. , OLIVER IAN , BLEEHEN STANLEY S. , MAC NEIL SHEILA
Published: July 2006

In vitro melanocyte‐stimulating hormone (MSH) stimulates melanogenesis in some, but not all, melanocytes and melanoma cells. In an attempt to explain this variation in response to αMSH, we examined cyclic adenosine monophosphate (cAMP) accumulation, tyrosinase activity, and melanin production in primary (1°) murine B16 melanoma cells and in two B16 cell lines (B16 F1 and B16 F10) that are known to respond to αMSH. In vivo all three B16 melanoma cell types produced pigmented tumours. In vitro αMSH increased tyrosinase activity and melanin content in the F1 and F10 cells but not in the B16 1° cells. αMSH, however, increased cAMP production in all three cell types, confirming that the inability of B16 1° cells to produce melanin in response to αMSH is not due to a lack of αMSH receptors or cAMP response to αMSH. Further, we present evidence for a separate pathway of melanogenesis that is independent of cAMP as calmodulin antagonists, which do not elevate cAMP, increased tyrosinase activity, and melanin production in both 1° and F1 cells.
Drug‐Induced and Genetic Hypermelanism: Effects on Pigment Cell Differentiation
Authors: FROST SALLY K. , BORCHERT MONIKA , CARSON MARY KAY
Published: July 2006

Allopurinol, a drug that inhibits the enzyme xanthine dehydrogenase (XDH), is known to cause hypermelanism in the axolotl. The hypermelanistic condition that results from allopurinol treatment is similar in most respects to the phenotype that results from the action of the melanoid (m) gene in axolotls. On the basis of structural and biochemical studies, it now seems clear that genetic and drug‐induced hypermelanism are the same in the following ways. 1) Both types of melanism result in the production of more than normal amounts of melanin and more melanin‐containing cells (melanophores). 2) In both cases the amount of pteridine‐associated yellow pigment declines during development, and this is associated directly with fine structural changes that occur within the pigment organelles (pterinosomes) of yellow pigment cells (xanthophores). 3) In both cases the hypermelanistic condition results in the suppression of reflecting pigment cell (iridophore) differentiation. 4) Both conditions have now been linked directly to depressed levels of XDH activity. Thus both genetic and drug‐induced hypermelanism result in alterations in the normal differentiation of all three pigment cell types and the subsequent disruption of normal pigment pattern formation. The possible significance of these findings with regard to factors known or suspected to direct the migration and/or differentiation of neural crest‐derived pigment cells is discussed.
New Thermal Neutron Capture Therapy for Malignant Melanoma: Melanogenesis‐Seeking 10B Molecule‐Melanoma Cell Interaction From In Vitro to First Clinical Trial
Authors: MISHIMA YUTAKA , ICHIHASHI MASAMITSU , HATTA SUSUMU , HONDA CHIHIRO , YAMAMURA KEIZO , NAKAGAWA TOSHIO
Published: July 2006

Human melanoma regression by single thermal neutron capture therapy (NCT) using melanoma‐seeking 10B compounds has been achieved. Since 1972, the aim of my team has been to synthesize tumor‐seeking 10B‐compounds possessing selective affinity for specific metabolic activity of the target cancer cells. Once the melanoma takes up these 10B compounds, thermal neutrons, which cause insignificant cell damage, are easily absorbed by nonradioactive 10B, inducing the 10B(n,α)7Li reaction and releasing the high LET particles to 14 μ melanoma cell diameter, destroying the tumor without damaging surrounding tissue. Radio‐biological and preclinical studies culminated in the first successful human NCT treatment, with no recurrence of the treated melanoma since July, 1987.
Determination of the Concentration of Complex Boronated Compounds in Biological Tissues by Inductively Coupled Plasma Atomic Emission Spectrometry
Authors: TAMAT SWASONO R. , MOORE DOUGLAS E. , ALLEN BARRY J.
Published: July 2006

The application of inductively coupled plasma atomic emission spectrometry (ICP‐AES) to the determination of the concentration of complex boron‐containing compounds in biological tissue samples is described. Tissue digestion is achieved with perchloric acid and hydrogen peroxide in 1 hr at 75deg;C. The ICP‐AES method gave a linear response for elemental boron concentration in the range 0.05 to 100 ppm and does not require the reduction of the boron to a simple species, such as boric acid. Complete recovery of boron in complex boron cluster compounds was obtained. The procedure has been applied to the determination of the boron content in compounds synthesised for neutron capture therapy and is suitable for use in biodistribution studies of such compounds.
Neutron Irradiation of Human Melanoma Cells
Authors: BROWN KEITH , MOUNTFORD MAX H. , ALLEN BARRY J. , MISHIMA YUTAKA , ICHIHASHI MASAMITSU , PARSONS PETER
Published: July 2006

The biological characteristics and in vitro radiosensitivity of melanoma cells to thermal neutrons were investigated as a guide to the effectiveness of boron neutron capture therapy. Plateau phase cultures of three human malignant melanoma‐established cell lines were examined for cell density at confluence, doubling time, cell cycle parameters, chromosome constitution, and melanin content. Cell survival dose‐response curves, for cells preincubated in the presence or absence of p‐boronophenylalanine HCl (10B1‐BPA), were measured over the dose range 0.6–8.0 Gy (N +γ). The neutron fluence rate was 2.6 ± 109 n/cm2/s and the total dose rate 3.7 Gy/h (31%γ). Considerable differences were observed in the morphology and cellular properties of the cell lines. Two cell lines (96E and 96L) were amelanotic, and one was melanotic (418). An enhanced killing for neutron irradiation was found only for the melanotic cells after 20 h preincubation with 10 μg/ml 10B1‐BPA. In view of the doubling times of the cell lines of about 23 h (96E and 96L) or of 36 h (418), it seems likely that an increased boron uptake, and hence increased radiosensitivity, might result if the preincubation period with 10B1‐BPA is extended to several hours longer than the respective cell cycle times.
Relative Biological Effectiveness (RBE) of Thermal Neutron Capture Therapy of Cultured B‐16 Melanoma Cells Preincubated With 10B‐Paraboronophenylalanine
Authors: ICHIHASHI MASAMITSU , SASASE AKIHIRO , HIRAMOTO TAKEAKI , FUNASAKA YOKO , HATTA SUSUMU , MISHIMA YUTAKA , KOBAYASHI TOHORU , FUKUDA HIROSHI , YOSHINO KAZUO
Published: July 2006

An experimental study of the relative biological effectiveness (RBE) of thermal neutron capture therapy (TNCT) for melanoma cell inactivation using 10B1‐paraboronophenylalanine (10B1‐BPA) was carried out to demonstrate a high therapeutic effect of TNCT, compared with that of fast neutron. Cells preincubated with or without 10B1‐BPA at a concentration of 50 μg/ml for 20 h were irradiated with 60Co gamma‐ray, fast neutron or thermal neutron. The absorbed dose of the cells from thermal neutron was calculated by Kobayashi's model. The D0 value of fast neutron was 1.07 Gy, and the D0s of thermal neutron radiation with or without preincubation of the cells with 10B1‐BPA were 0.46 Gy or 0.67 Gy, respectively. The RBEs of fast neutron, thermal neutron beams, and neutron capture therapy relative to 60Co gamma‐ray were calculated as 2.78, 4.18, and 6.15 at 0.1 surviving fraction, respectively. These results indicate radiobiologically that thermal neutron capture therapy using 10B1‐BPA is an excellent radiation therapy for malignant melanoma.
Review: Biological Effectiveness of Thermal Neutrons and 10B(n,α)7Li Reaction on Cultured Cells
Authors: FUKUDA HIROSHI , ICHIHASHI MASAMITSU , KOBAYASHI TOORU , MATSUZAWA DAIJU , KANDA KEIJI , MISHIMA YUTAKA
Published: July 2006

There are only a few reports on the relative biological effectiveness (RBE) of thermal neutrons and 10B(n,α)7Li reactions either in vitro or in vivo. The data in this paper summarize almost all previously published in vitro data. Because only a few reactors are available for biomedical purposes, it is difficult to make a comparison of data from experiments using the same kind of radiation, and also to make a comparison of data from experiments using the different kinds of radiations. However, it is indispensable for boron neutron capture therapy to make a radiobiological analysis. More intensive study, including repair process and oxygen effect, is necessary for establishing the fundamental basis of the clinical application of boron neutron capture therapy.
Characteristics of Malignant Melanoma Cells in the Treatment With Fast Neutrons
Authors: TSUNEMOTO HIROSHI , MORITA SHINROKU , MORI SHUNJI
Published: July 2006

The radioresistance of malignant melanoma cells has been explained by the wide shoulder of the dose‐cell‐survival curve of the cells exposed to photon beams. Fast neutrons, 30 MeV d‐Be, were used to treat patients who had malignant melanoma in order to confirm the biological effects of high linear energy transfer (LET) radiation for tumor control.

Seventy‐two patients suffering from malignant melanoma participated in the clinical trials with fast neutrons between November 1975 and December 1986. Of 72 patients, 45 had melanoma of the skin, 20 had melanoma of the head and neck, and seven had choroidal melanoma.

Five‐year survival rate of the patients who had previously untreated melanoma of the skin was 61% and for patients who received postoperative irradiation, it was 35.7% whereas no patients who had recurrent tumor survived over 4 years. Of 22 patients who had melanoma of the skin, stage I, local control in four cases was achieved by irradiation alone, whereas local control was achieved in 17 of 18 patients who required salvage surgery after fast‐neutron therapy. The results of pathological studies performed with specimens obtained from salvage surgery have shown that melanoma cells growing in intradermal tissue are radio‐resistant, compared with cells growing in intraepidermal tissue. This might suggest that melanoma cells acquire radioresistance when the connective tissue is involved.

Five‐year survival rate of the patients who had locally advanced melanoma of the head and neck, previously untreated, was 15.4%. Radiation therapy with accelerated protons was suitable for patients suffering from choroidal melanoma.
Induction of DNA‐Protein Crosslinks in Melanotic Cloudman S91 Mouse Melanoma Cells and EMT6 Mouse Mammary Carcinoma Cells by Monochromatic 254 and 405 nm Light
Authors: HILL HELENE Z. , PEAK JENNIFER G. , PEAK MEYRICK J.
Published: July 2006

The rates of induction of DNA‐protein crosslinks (DPC) by monochromatic radiation at 254 and 405 nm were compared in melanotic S91 mouse melanoma cells and EMT6 mouse mammary carcinoma cells. At 254 nm, the rates of induction of DPC are the same in the two cell lines, whereas, at 405 nm, the rate of induction of DPC in the melanotic cells is considerably less than that in the nonmelanotic cells. Since the major difference in the two cell lines with respect to absorption is melanin, the latter finding implies that intracellular melanin can protect against this DNA damage caused by a component of environmental carcinogenic solar radiation.
Speed of Growth of Melanoma: Statistical Analysis of the Average Ages of Patient Groups
Authors: PAUL EBERHARD , PAUSCH ANDREAS , BÖDEKER ROLF‐HASSO
Published: July 2006

Based on data from 1,657 cases, the average age of patients with melanoma of the same type, level, resp. thickness was calculated. It was shown that the average age of the melanoma patients increased with progressive tumor growth, i.e., with increasing level and thickness. The time span for thin (< 0.75 mm thickness), superficial spreading melanoma (SSM) to reach the level of a far‐advanced tumor with a thickness of more than 3.00 mm was 7.8 years. For nodular melanomas (NM), the corresponding period was 9.5 years. Longer intervals were determined by analysis of the data according to tumor levels. The difference in the average age of patients with early invasive SSM (level II) as compared with patients with level V tumors was 11.4 years. Patients with level V NM were on the average 10.0 years older than patients with level III NM. Differences in the average age of patients with SSM or NM from one level to the other ranged between 3 and 4 years (median: 3.9 years). The differences in the thickness of the groups were similar (median: 3.1 years).
Alpha‐Melanocyte‐Stimulating Hormone Immunoreactivity in Human Melanoma Metastases Extracts
Authors: GHANEM G. , VERSTEGEN J. , LIBERT A. , ARNOULD R. , LEJEUNE F.
Published: July 2006

Seven human melanoma metastases were extracted in order to check the possible presence of any α‐melanocyte stimulating hormone (MSH) immunoreactivity. The aim of that study was to provide some explanation for, mainly, two observations that we have already made and reported: 1) increased plasma α‐MSH levels in melanoma of tumour‐bearing patients as compared with tumour‐free patients; 2) the presence of specific α‐MSH receptors on human melanoma cells in culture.

We could measure large amounts of immunoreactive α‐MSH in all tumours ranging from 0.31 to 4.27 pmoles per g of wet tissue. Further identification of the extracted material by high‐performance liquid chromatography revealed compounds of higher molecular weight and more hydrophobic than synthetic α‐MSH. In addition, purified extracts could also displace 125I‐labelled α‐MSH from its cellular binding sites in an α‐MSH specific radio‐receptor binding assay. Our findings would suggest a possible presence of some hormone precursor(s) inside the melanoma tumours.
Expression of Virally Transduced Mouse Tyrosinase in Tyrosinase‐Negative Chick Embryo Melanocytes in Culture
Authors: WHITAKER BETH A. , FREW TIMOTHY J. , GREENHOUSE JACK J. , HUGHES STEPHEN H. , YAMAMOTO HIROAKI , TAKEUCHI TAKUJI , BRUMBAUGH JOHN A.
Published: July 2006

A cDNA encoding mouse tyrosinase was inserted into a plasmid containing the provirus of a replication competent avian leukosis virus (ALV). A viral stock produced from the plasmid was used to infect cultured tyrosinase‐negative (ca/ca) unpigmented chick embryo melanocytes. Five days after infection many cells were producing very dark discrete melanosomes.
Alteration of Glutathione Level in Human Melanoma Cells: Effect of N‐Acetyl‐L‐Cysteine and its Analogues
Authors: KARG ESZTER , TUNEK ANDERS , BRÖTELL HARALD , ROSENGREN EVALD , RORSMAN HANS
Published: July 2006

The effects of N‐acetyl‐l‐cysteine (l‐NAC), N,N‐diacetyl‐l‐cystine (oxidized form of l‐NAC) and N‐acetyl‐d‐cysteine on the intracellular glutathione (GSH) level and their toxicity were investigated in the human melanoma cell culture IGR1. l‐NAC applied in 3 mM concentration for 24 hr decreased; when applied for 48 hr it did not alter the intracellular GSH level. Treatment with 1 mM l‐NAC for 24 hr had no effect on cellular glutathione, whereas the same concentration applied for 48 hr resulted in an increase in the level of GSH. Both concentrations also induced cell injury as determined by protein assay and trypan blue staining. N,N‐diacetyl‐l‐cystine (0.5 and 1.5 mM, 24 hr) induced a decrease in cellular glutathione content without any apparent cell toxicity. d‐NAC (1 and 3 mM, 24 hr) did not influence the GSH level of the melanoma cells; however, it had toxic effects resulting in cell loss.
Differentiation of Hairbulb Pigment Cell Melanosomes in Compound Agouti and Albino Locus Mouse Mutants (Ay, a, c2J; C57BL/6J)
Authors: GRANHOLM NELS H. , JAPS ROBERT A. , KAPPENMAN KARL E.
Published: July 2006

Our objective was to determine using electron microscopy how nonagouti (a), lethal yellow (Ar), and albino (c2J) genes affect the program of mouse hairbulb melanosome differentiation; 1,921 hairbulb melanosomes from four genotypes (a/a C/C = B,Ay/a C/C = Y, a/a c2J/c2J= BA, and Ay/a c2J/c2J= YA) were scored for developmental stage, length, and width.

Qualitative and quantitative electron microscopy revealed the following. An albino locus‐induced diminution of melanosome size suggests that the albino locus is involved in structural features of melanosomes not directly related to the synthesis and deployment of tyrosinase. Ratio data on melanosome length‐to‐width confirm that the agouti locus determines melanosome shape, either spherical or elliptical; melanization is not required for melanosomes to achieve their agouti‐locus‐determined shapes. YA (Ay/a c2J/c2J) melanosomes, characterized by poorly organized matrices, absence of active tyrosinase, unusually large membrane invaginations, and significantly smaller dimensions than those of BA (a/a c2J/c2J), showed additive effects of both Ay and c2J alleles.

These data suggest that the albino locus plays a structural as well as functional (tyrosinase) role in the differentiation of mouse hairbulb melanosomes. The agouti locus, even in the absence of melanization, directs melanosome shape either via synthesis and deployment of agouti‐locus‐encoded matrix proteins or by other structural factors. The additive effects of Ay and c2J alleles in compound YA mutants document the importance of specific interactions both functional and structural between agouti and albino loci.
Characterization of the Yellow Pigment in the Axanthic Mutant of the Mexican Axolotl, Ambystoma mexicanum
Authors: BUKOWSKI LAUREN , ERICKSON KAREN , LYERLA TIMOTHY A.
Published: July 2006

The yellow pigment observed in older axanthic (ax/ax) mutant Mexican axolotls (Ambystoma mexicanum) was analyzed by thin layer chromatography and by spectrofluorometry of its acetyl derivative. Ethanol extracts from the skin of axanthic animals were acetylated and the chloroform‐soluble portion of the product mixture was compared with a chloroform solution of an authentic riboflavin tetraacetateo standard prepared in the same manner. The pigment in these two solutions behaved identically on thin layer chromatograms and in fluorescent emission spectroscopy. This confirms that the yellow pigment seen in these genetically axanthic animals is riboflavin and, since it cannot be synthesized by the animal, must be derived from the diet.
4‐S‐Cysteaminylphenol and its Analogues as Substrates for Tyrosinase and Monoamine Oxidase
Authors: PANKOVICH JAMES M. , JIMBOW KOWICHI , ITO SHOSUKE
Published: July 2006

A phenolic amine compound, 4‐S‐cysteaminylphenol (4‐S‐CAP), was found to cause a selective destruction of follicular melanocytes. It was also recently found that 4‐S‐CAP can be a substrate for both tyrosinase and plasma monoamine oxidase (MAO). Both of these enzymes are capable of producing cytotoxic intermediates through their interaction with 4‐S‐CAP. To study the mechanism of selective melanocytotoxicity of phenolic amine compounds, we compared the in vivo depigmenting potency of 4‐S‐CAP and its three analogues; i.e., 4‐S‐HomoCAP, α‐methyl(Me)‐4‐S‐CAP and N,N‐dimethyl(DiMe)‐4‐S‐CAP, using black hair follicles. All four of these phenolic amine compounds possessed depigmenting potency. In this study we examined the kinetics of tyrosinase and MAO by these four compounds. 4‐S‐CAP and 4‐S‐HomoCAP were the substrates of both tyrosinase and MAO, whereas α‐Me‐4‐S‐CAP and N,N‐DiMe‐4‐S‐CAP were the substrates of tyrosinase alone. The rate of o‐quinone formation by tyrosinase was not in parallel to the in vivo depigmenting potency of the tested compounds. It is therefore indicated that plasma MAO is not the enzyme directly responsible for the production of the melanocytotoxic intermediates from the phenolic amine compounds. We also found that the observed in vivo depigmentation results from complex processes involving the amount of o‐quinone formed and the intracellular interaction of o‐quinone with protein species.