bluuebunny/crossref_metadata_2025 huggingface dataset:
Winter browsing on Alaska feltleaf willow twigs improves leaf nutritional value for snowshoe hares in summer
Authors: Bryant John P.
Published: December 2004

In boreal forests, browsing by mammals on winter‐dormant twigs increases leaf nitrogen, leaf greenness, and leaf size. This suggests browsing reduces competition among meristems for mineral nutrients, and in particular, competition for nitrogen. Winter browsing also reduces the shoot carbohydrate reserves used by leaves to produce condensed tannin. These effects of winter browsing are predicted to improve the nutritional value of leaves for mammals because they increase the mass of digestible nitrogen in leaves. This hypothesis was tested using Alaska feltleaf willow and the snowshoe hare as the experimental system. Six in vivo indicators of leaf nutritional quality were used to compare leaves from winter‐browsed plants with leaves from unbrowsed plants. The indicators used were dry matter intake, nitrogen intake, condensed tannin intake, dry matter digestibility, apparent digestibility of nitrogen and nitrogen retention. The results obtained were in agreement with the above hypothesis. In early summer, at the time snowshoe hares and other northern herbivores reproduce, hares fed leaves from browsed plants consumed more nitrogen, digested more of the nitrogen they consumed, and retained more of the nitrogen they digested than did hares fed leaves from unbrowsed plants. The high nitrogen content and low tannin content of leaves from browsed plants may explain this browsing caused increase in leaf nutritional value. How these positive effects of winter browsing on snowshoe hare nutrition at the time of reproduction might affect hare population dynamics are briefly discussed.
Influence of pulsed resources and marine subsidies on insular rodent populations
Authors: Stapp Paul , Polis Gary A.
Published: December 2004

Inputs of marine resources contribute to high consumer densities on small, barren islands in the arid Gulf of California, Mexico. Episodes of rainfall associated with El Niño Southern Oscillation (ENSO) events, however, stimulate plant growth and seed production and replenish soil detritus and seed banks. We studied the effects of marine inputs and pulsed ENSO resources on rodent populations on islands before, during and after the strong 1997–1998 ENSO event. Stable isotope analysis was used to determine rodent diets. During dry years, P. maniculatus consumed marine prey near shore and on small islands, and were much more abundant in these areas than farther inland and on larger islands. Captures were particularly concentrated near shore on three islands inhabited by Chaetodipus rudinoris, a granivore that was numerous in inland areas. Following the ENSO, Peromyscus maniculatus increased in abundance by 408%, compared to only 160% for C. rudinoris, and new individuals invaded inland areas. P. maniculatus populations declined sharply the following year, however, whereas C. rudinoris populations remained relatively stable. In response to ENSO conditions, P. maniculatus ate more seeds on islands with C. rudinoris than on islands without C. rudinoris. P. maniculatus also increased less markedly and declined more quickly in abundance where C. rudinoris was present. We speculate that P. maniculatus is capable of rapid numerical response to resource pulses but depends on marine foods during dry years. C. rudinoris is restricted to islands with sufficient seed resources, but maintains stable populations by exploiting low‐density seeds and caching seeds from wet years. On islands with both species, C. rudinoris restricts P. maniculatus to near‐shore areas via interference, but spillover consumption of seeds by subsidized P. maniculatus may limit the response of C. rudinoris to ENSO resources. Combined with differences in life history and dispersal abilities, these ecological factors help explain the distinct biogeographic distributions of these rodents on Gulf islands.
Safety in numbers for secondary prey populations: an experimental test using egg predation by small mammals in New Zealand
Authors: Jones Christopher
Published: December 2004

New Zealand's native avifauna is threatened by introduced mammalian predators. Native species are often not the primary prey of these predators, which depend on introduced mice and rabbits as their primary food source. Theoretical models predict that predation risk for a subsidiary, or “secondary” prey species is inversely proportional to its population size. This prediction was tested by a quasi‐natural experiment in which four different sized prey “colonies” were constructed at four existing sooty shearwater breeding sites. Domestic hens' eggs were placed in shearwater burrows immediately following the shearwater breeding season and egg predation rates monitored at five, ten and fifteen days. Treatments were switched between sites and the experiment run for a second time after a two‐week stand‐down period. The net effect of increasing colony size was to lower individual risk of predation. The larger number of individuals present served to effectively “buffer,” or dilute, per‐capita predation risk from predators whose numbers are fixed by extraneous factors: chiefly the abundance of their primary prey. Although eggs were removed more slowly from smaller colonies than from larger ones, each loss had a greater per‐capita effect on individual mortality risk. The inverse density dependent relationship found between colony size and predation risk implies that predator population dynamics are largely independent of secondary prey numbers. Abundant introduced predators can therefore easily drive a small secondary prey population to extinction. Control of primary prey populations may be an important management tool in these circumstances.
The response of a three trophic level soil food web to the identity and diversity of plant species and functional groups
Authors: Wardle David A. , Yeates Gregor W. , Williamson Wendy , Bonner Karen I.
Published: December 2004

Despite considerable recent interest in how biodiversity may influence ecosystem properties, the issue of how plant diversity and composition may affect multiple trophic levels in soil food webs remains essentially unexplored. We conducted a glasshouse experiment in which three plant species of each of three functional groups (grasses, N‐fixing legumes and forbs) were grown in monoculture and in mixtures of three species (with the three species being in the same or different functional groups) and all nine species. Plant species identity had important effects on the biomasses or population densities of belowground primary consumers (microbial biomass, herbivorous nematodes) and two groups of secondary consumers (microbe‐feeding nematodes and enchytraeids); the third consumer trophic level (predatory nematodes) was marginally not significantly affected at P=0.05. Plant species also influenced the relative importance of the bacterial‐based and fungal‐based energy channels for both the primary and secondary consumer trophic levels. Within‐group diversity of only the soil microflora and herbivorous nematodes (both representing the basal consumer trophic level) were affected by plant species identity. However, community composition within all trophic groupings considered (herbivorous nematodes, microbes, microbe‐feeding nematodes, predatory nematodes) was strongly influenced by what plant species were present. Despite the strong responses of the soil biota to plant species identity, there were few effects of plant species or functional group richness on any of the belowground response variables measured. Further, net primary productivity (NPP) was unaffected by plant diversity. Since some belowground response variables were correlated with NPP across treatments, it is suggested that belowground responses to plant diversity might become more apparent in situations when NPP itself responds to plant diversity. Our results point to plant species identity as having important multitrophic effects on soil food webs, both at the whole trophic group and within‐group levels of resolution, and suggest that differences in plant traits across species may be important in driving the decomposer subsystem.
Stem Cell Factor and/or Endothelin‐3 Dependent Immortal Melanoblast and Melanocyte Populations Derived From Mouse Neural Crest Cells
Authors: KAWA YOKO , ITO MASARU , ONO HIROTAKE , ASANO MARI , TAKANO NAGAKO , OOKA SHIHO , WATABE HIDENORI , HOSAKA ERI , BABA TAKAKO , KUBOTA YASUO , MIZOGUCHI MASAKO
Published: December 2004

Stem cell factor (SCF) and endothelin‐3 (ET3) are both necessary for melanocyte development. In order to obtain immortal cell populations of melanoblasts that can survive without feeder cells, we first obtained an immortal cell population of neural crest cells (NCCs) from Sl/+ and +/+ mice of strain WB by incubating with a culture medium supplemented with SCF and ET3, and then we designated them as NCC‐SE3 cells. NCC‐SE3 cells were bipolar, polygonal, or round in shape and possessed melanosomes of stages I–III (mainly stage I). They were positive to dihydroxyphenylalanine (DOPA) reaction and expressed KIT (a receptor tyrosine kinase), tyrosinase, tyrosinase‐related protein‐1 (TRP1), tyrosinase‐related protein‐2 (TRP2), and endothelin‐B receptor (ETRB) as determined by immunostaining. We next cultured NCC‐SE3 cells by changing culture medium from the one supplemented with SCF+ET3 to the one supplemented with SCF or ET3. NCC‐SE3 cells cultured with ET3 alone, designated as NCC‐E3 cells, were bipolar in shape and had mainly stage II melanosomes and expressed the same proteins as did NCC‐SE3 cells. However, NCC‐SE3 cells cultured with SCF alone, designated as NCC‐S4.1 cells, were polygonal in shape and had mainly stage I melanosomes. They are thought to be more immature because they were positive to KIT, TRP1, and TRP2, but not to ETRB, tyrosinase, and DOPA reaction. When 12‐O‐tetradecanoyl phorbol‐13‐acetate and cholera toxin were added to the culture medium, NCC‐S4.1 cells changed shape from polygonal to bipolar and became DOPA‐positive. This suggests that NCC‐S4.1 cells are melanoblasts that have the potential to differentiate into melanocytes. These cell populations will be extremely useful to study factors that affect melanocyte development and melanogenesis.
Regulation of Pigment Cell‐Specific Gene Expression by MITF
Authors: SHIBAHARA SHIGEKI , YASUMOTO KEN‐ICHI , AMAE SHINTARO , UDONO TETSUO , WATANABE KEN‐ICHI , SAITO HIDEO , TAKEDA KAZUHISA
Published: December 2004

Melanocyte and retinal pigment epithelium (RPE) specifically express tyrosinase and other melanin‐producing enzymes. Microphthalmia‐associated transcription factor (Mitf), encoded at the mouse microphthalmia locus, regulates the development and survival of many cell types, including melanocyte and RPE. MITF, the human homolog of Mitf, consists of at least four isoforms with distinct amino‐termini, referred to as A, MITF‐C, MITF‐H, and MITF‐M. MITF‐M is exclusively expressed in melanocytes and melanoma cells, and thus represents the melanocyte lineage‐specific isoform. In contrast, other isoforms are expressed in many cell types so far examined. These isoforms appear to function as transcriptional activators of the melanogenesis genes, as assessed by transient transfection assays in cultured cells. Functional significance of Mitf‐M in melanocyte differentiation was verified by the molecular lesion of black‐eyed white Mitfmi‐bw mice, which lack melanocytes but have normal RPE. The Mitf gene of this mutant has the insertion of an L1 retrotransposable element in the intron between exon 3 and exon 4, leading to complete repression of Mitf‐M mRNA expression. Taken together, these results suggest that melanogenesis in melanocyte and RPE is regulated by separate Mitf/MITF isoforms. Recent findings on the multiplicity of MITF isoforms are summarized.
Chemical Analysis of Melanins and its Application to the Study of the Regulation of Melanogenesis
Authors: ITO SHOSUKE , WAKAMATSU KAZUMASA , OZEKI HIROYUKI
Published: December 2004

Melanins are difficult to characterize because of their intractable chemical properties, the heterogeneity in their structural features, and the lack of methods to split melanin polymers into monomer units. To overcome this difficulty, we developed a rapid and sensitive method for quantitatively analyzing eumelanin and pheomelanin in biological samples that is based on the formation of pyrrole‐2,3,5‐tricarboxylic acid and/or aminohydroxyphenylalanine followed by HPLC determination. The method has been applied to the study of melanogenesis. The results summarized in this review are: 1) Biochemical studies show that in the process of mixed melanogenesis, cysteinyldopas are produced first, which are then oxidized to give pheomelanin; following cysteine depletion, eumelanin is then deposited on the preformed pheomelanin. 2) In vitro and in vivo studies show that tyrosinase activity is the most important factor that regulates the switch of melanogenesis, with lower tyrosinase activities favoring pheomelanogenesis; further suppression of melanogenesis results in a lack of pigment production. 3) In cultured melanocytes, the concentrations of tyrosine and cysteine, and their ratio in the medium, are important in determining the concentrations of eumelanin and pheomelanin produced and their ratio in the cells. In conclusion, our HPLC microanalytical method for characterizing eumelanin and pheomelanin has become a useful tool for the study of melanogenesis.
Molecular Bases of Congenital Hypopigmentary Disorders in Humans and Oculocutaneous Albinism 1 in Japan
Authors: TOMITA YASUSHI , MIYAMURA YOSHINORI , KONO MICHIHIRO , NAKAMURA RIEKO , MATSUNAGA JUN
Published: December 2004

The molecular bases of various types of congenital hypopigmentary disorders have been clarified in the past 10 years. Homozygous gene mutations of enzymes functional in melanogenesis such as tyrosinase, P protein and DHICA oxidase, result in oculocutaneous albinism (OCA) 1, OCA 2, and OCA 3, respectively. The genes responsible for Hermansky‐Pudlak syndrome (HPS) and Chediak‐Higashi syndrome (CHS) have also recently been isolated and cloned. The transcription factor paired box 3 (PAX3) works at the promoter region of the microphthalmia‐associated transcription factor (MITF) gene, and the MITF transcription factor orders the expression of c‐kit, which encodes the receptor for stem‐cell factor, which in turn stimulates melanoblast migration from the neural tube to the skin in the embryo. Heterozygous mutations of PAX3, MITF, or c‐kit genes induce Waardenburg syndrome (WS) 1/3, WS 2 or Piebaldism, respectively. A defect of endothelin‐3 or the endothelin‐B receptor produces WS 4. In our examination of 26 OCA 1 patients in Japan, all were found to have homozygous or heterozygous tyrosinase gene mutations at codons 77 or 310. Therefore, mutations at codons 77 and 310 are the major ones in Japanese patients with OCA 1. An autosomal dominant pigmentary disease of dyschromatosis symmetrica hereditaria (DSH) is well known in Japan, and is characterized by a mixture of hypo‐ and hyper‐pigmented macules of various sizes on the backs of the hands and feet. The disease gene and its chromosomal localization have not been identified yet. Our trial of linkage analysis and positional cloning to determine the disease gene is presented.
UVA, Pheomelanin and the Carcinogenesis of Melanoma
Authors: HILL HELENE Z. , HILL GEORGE J.
Published: December 2004

Cloudman S91 mouse melanoma cells vary in constitutive and inducible melanin levels. Survival, mutation induction and DNA damage were quantitated after exposure to UVB, UVA and FS20 lamps. Assuming that the observed differences are related to melanin, induced pigment is photo‐protective for survival and mutation after UVB and FS20 exposure, and is photosensitizing for survival after UVA exposure. No changes in pyrimidine dimers could be measured. DNA damage in pigmented mouse melanocytes (melan‐a and melan‐b) was greater than that in albino melanocytes (melan‐c) after UVB and FS20, and the pigmented cells were more sensitive to killing. Pigment appears to be protective for killing by UVA in these melanocytes. Human melanocytes from different skin types vary in both melanin amount and composition (eu‐ and pheomelanin). Effects of pigmentation on UVB responses are unclear. In UVA, heavily pigmented cells have more DNA damage than lightly pigmented cells, but are resistant to killing. Increased pheomelanin photosensitizes DNA damage in lightly pigmented cells. Since eumelanin predominates in the mouse melanoma cells and melanocytes, they are less likely than human cells to provide a satisfactory model for human solar melanomagenesis. In order to understand the mechanism of photocarcinogenesis of melanoma, melanins in human melanocytes from different pigment types should be carefully quantitated and characterized. Mutations induced in them by solar wavelength‐emitting lamps with well‐characterized spectra should be measured, and mutant DNA should be sequenced to determine the nature of the solar‐induced lesions. Research should focus on UVA and pheomelanin.
Microphthalmia: A Signal Responsive Transcriptional Regulator in Development
Authors: FISHER DAVID E.
Published: December 2004

The transcription factor Microphthalmia (Mi) is a helix‐loop‐helix protein which plays an essential role in the development and subsequent function of neural crest‐derived melanocytes. Since its discovery as a mutant allele producing mice devoid of viable melanocytes, Mi has emerged as the gene whose mutation is responsible for the human pigmentation condition Waardenburg Syndrome IIa, as well as a variety of cellular defects involving retinal pigment epithelium, osteoclasts, and mast cells. As discussed here, Mi has recently been recognized to be targeted by several signaling pathways of importance to melanocytes, those activated by melanocyte stimulating hormone (MSH) and Steel factor. While these two pathways profoundly modulate Mi activity, they do so via strikingly different mechanisms. The differences and similarities of these responses highlight the likely roles of Mi in influencing both pigmentation and proliferation/survival. These effects are also of significance in human melanoma, a tumor for which Mi appears to be an extremely sensitive and specific marker.
Dual Control of Melanogenesis and Melanoma Growth: Overview
Authors: MISHIMA YUTAKA , KONDOH HIROFUMI
Published: December 2004

Utilizing increased melanin pigmentation and accentuated melanogenesis seen in malignant melanoma, we newly developed melanoma‐selective boron neutron capture therapy (BNCT) after designing and synthesizing the 10B‐DOPA analogue, 10B‐p‐boronophenylalanine (10B‐BPA). After multi‐disciplined and extensive basic and pre‐clinical investigations, we successfully treated 18 cases of human melanoma.

Recently, we found that accentuated synthesis of melanin monomers, richest within coated vesicles (CV) in melanoma cells, plays a critical role in attracting 10B‐BPA through chemical complex formation of monomers and 10B‐BPA. CV are indeed BPA‐localizing organelles. This led us to the new clinical endeavor that BPA may possess the potential ability to suppress melanin polymer formation through ‘melanin monomer trapping’ out of the melanogenic pathway which is highly regulated by the function of CV in pigment cells. It was soon found that melanin polymer formation can be suppressed by BPA at the chemical and cellular levels, then at the clinical level.

Our discovery, that single molecule 10B‐BPA possesses the dual nature of eradication of melanoma with BNCT and suppression of melanin hyperpigmentation, resulted from pursuing bilateral feedback at each stage from pure science to clinical application and vice versa.

A further example of bilateral feedback is the development of gene‐transfer applied BNCT (gBNCT). This also has its roots in clinical hurdles faced in treating amelanotic melanomas by 10B‐BPA BNCT. The transfer of tyrosinase and melanin monomer synthesis‐related genes into target cancer cells has produced more effective BNCT and may lead to gBNCT for non‐melanoma cancers.
Relative Molecular Similarity in Selected Chemical Carcinogens and the Nucleoside Triphosphate Chain
Authors: Williams Wynford Robert
Published: December 2004

Abstract: Several markers of cell toxicity are useful as screening tests for epigenetic carcinogens. The direct effects of chemicals on ATPase and GTPase function are pertinent to the early stages of carcinogenesis. Interference with triphosphate‐diphosphate exchange mechanisms may result from the interaction of carcinogens with the substrate triphosphate chain. To investigate this hypothesis, a computational chemistry programme is used in this study to investigate molecular similarity in ATPase inhibitors, carcinogens and tumour promoters, in relation to the nucleoside triphosphate chain. The results show that atoms in the investigated molecular structures superimpose on sets of oxygen atoms in the triphosphate chain with interatomic distances <0.3A. Relative molecular similarity to the substrate triphosphate chain is discussed in terms of the established inhibitory properties of carcinogens/tumour promoters on ATPase function, the carcinogen/tumour promoting properties of ATPase inhibitors and the prediction of carcinogenic activity from chemical structure.
Effects of Dietary β‐Cyclodextrin in Hypercholesterolaemic Rats
Authors: García‐Mediavilla Victoria , Villares Carmen , Culebras Jesús M. , Bayón Jose E. , González‐Gallego Javier
Published: December 2004

Abstract: β‐Cyclodextrin is a compound that forms inclusion complexes with a variety of molecules, specially bile acids and sterols. This study examines the effects of β‐cyclodextrin on cholesterol and bile acid metabolism in hypercholesterolaemic rats. Male Wistar rats were divided into 4 groups that received during 7 weeks: control diet, 2% cholesterol diet (A), A+2.5% β‐cyclodextrin (B) and A+5% β‐cyclodextrin (C). The cholesterol‐rich diet induced hepatomegaly and fatty liver and significantly reduced cholesterol, bile acid and phospholipid secretion. Addition of β‐cyclodextrin normalised biliary lipid secretion. Moreover, when compared to A, β‐cyclodextrin significantly lowered plasma phospholipid concentration (B: −21%; C: −29%) and the liver free/total cholesterol molar ratio (B: −40%; C: −38%), increased bile acid faecal output (B: +17%; C: +62%) and enhanced cholesterol 7α‐hydroxylase activity (B:+50%; C: +100%) and mRNA levels (B: +14%; C: +29%). 5% β‐cyclodextrin also reduced plasma triglycerides concentration (−38%). However, ALT and AST activities were significantly increased (B: +140% and +280%; C: +72% and +135%) and there was a high incidence of cell necrosis with portal inflammatory cell infiltration. Addition of β‐cyclodextrin to a cholesterol‐rich diet results in a triglyceride‐lowering action, enhancement of bile acid synthesis and excretion, and normalization of biliary lipid secretion, but produces a marked hepatotoxic effect.
Inactivation of Cholinesterase Induced by Chlorpromazine Cation Radicals
Authors: Muraoka Sanae , Miura Toshiaki
Published: December 2004

Abstract: To clarify the mechanism of the side effect of chlorpromazine, we examined the inactivation of cholinesterase induced by chlorpromazine. Cholinesterase was inactivated and its activity was lost in rat serum during interaction of chlorpromazine with horseradish peroxidase and H2O2. When chlorpromazine was oxidized by horseradish peroxidase and H2O2, the reaction solution colored pink and the visible absorption spectrum was consistent with the absorption spectrum of the chlorpromazine cation radical (CPZ·+). Adding cholinesterase immediately decreased the pink color of CPZ·+, indicating that CPZ·+ directly attacked cholinesterase to cause loss of the enzyme activity. Tryptophan residues in cholinesterase sharply decreased during the interaction of cholinesterase with horseradish peroxidase and H2O2. Presumably, loss of tryptophan residues changed the conformation of the cholinesterase protein and then the activity of the enzyme was lost. Other phenothiazine derivatives, including promethazine, triflupromazine, trifluoperazine, trimeprazine, thioridazine and perphenazine, also inactivated cholinesterase during the oxidation by horseradish peroxidase and H2O2. These results suggest that phenothiazine cation radicals participate in toxicological signs caused by the drugs.
Incorporation of the Food Mutagen 2‐Amino‐1‐Methyl‐6‐Phenylimidazo[4,5‐b]Pyridine (PhIP) into Fur and Correlation with Intestinal Tumourigenesis in Min/+ Mice
Authors: Steffensen Inger‐Lise , Janak Karel , Hegstad Solfrid , Andreassen Åshild , Paulsen Jan Erik , Reistad Ragnhild , Alexander Jan
Published: December 2004

Abstract: The purpose of this work was to correlate the amount of the food mutagen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) determined in mouse fur with the number of intestinal tumours induced by PhIP, to further evaluate incorporation of PhIP into hair as a putative exposure biomarker for food mutagens. We have previously shown that PhIP increases intestinal tumourigenesis in C57BL/6J‐Min/+ (Multiple Intestinal Neoplasia) mice. Fur was sampled from mice exposed according to various PhIP protocols, and the amount of PhIP in the fur was quantitated by high performance liquid chromatography – mass spectrometry (HPLC‐MS). A quantitative incorporation of PhIP in the fur was demonstrated after a single subcutaneous injection of PhIP, and between one and eight PhIP exposures either via direct subcutaneous injections or through breast milk from PhIP‐injected dams. However, after higher exposures, the amount of PhIP in the fur appeared to reach saturation. After low exposures to PhIP, the number of intestinal tumours correlated with the amount of PhIP in the fur of individual mice, whereas after higher exposures, the number of tumours was relatively higher than the amounts of incorporated PhIP in the fur. Other factors, e.g. amounts of reactive PhIP metabolites formed, are also determining the number of intestinal tumours. The demonstrated quantitative incorporation of PhIP into mice fur and the correlation with number of intestinal tumours at the lower exposures, indicate that determination of PhIP in human hair may be a suitable biomarker for exposure to dietary PhIP, which is found in human hair in 10−3 lower amounts than in these mice.
Toluene Depresses Plasma Corticosterone in Pregnant Rats
Authors: Hougaard Karin S. , Hansen Åse M. , Hass Ulla , Lund Søren P.
Published: December 2004

Abstract: Combined exposure to stressors and chemicals may result in synergistic effects. The effects of prenatal exposure to the organic solvent toluene resemble those observed in offspring of gestationally stressed dams, a possible common mechanism being transfer of stress‐/toluene‐induced increments of corticosteroids from the maternal to the foetal compartment. Pregnant rats were subjected to either 1500 ppm toluene 6 hr/day and/or a schedule of “Chronic mild stress” during the last two weeks of gestation. Exposure to toluene was associated with reduced birth weight and lower maternal weight gain, the latter being enhanced by maternal stress. A depressant effect of toluene on maternal corticosterone was observed, hence the study does not provide immediate evidence that transfer of elevated levels of corticosterone from the maternal to the foetal compartment mediates the effects of prenatal exposure to toluene.
Pharmacological Profile of the Vascular Responses to Dopamine in the Canine External Carotid Circulation*
Authors: Villalón Carlos M. , Ramírez‐San Juan Eduardo , Sánchez‐López Araceli , Bravo Guadalupe , Willems Edwin W. , Saxena Pramod R. , Centurión David
Published: December 2004

Abstract:The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10–310 μg min.−1) produced dose‐dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D1/2‐like receptor agonist apomorphine (1–310 μg min−1), but not by the D2‐like receptor agonist, bromocriptine (31–310 μg min.−1). In contrast, fenoldopam (1–310 μg min.−1, intracarotid), a D1‐like receptor agonist, produced dose‐dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α1/2; 2000 μg kg−1) or rauwolscine (α2; 100 μg kg−1), but remained unaffected after prazosin (α1; 100 μg kg−1) or haloperidol (D2‐like; 1000 μg kg−1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose‐dependentvasodilatorcomponent was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg−1each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg−1), propranolol (1000 μg kg−1) or vagosympathectomy, were abolished by the D1‐like receptor antagonist, SCH‐23390 (10 μg kg−1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg−1; −24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α2‐adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D1‐like receptors.
Regulation of 1‐α, 25‐Dihydroxyvitamin D3 on Interleukin‐6 and Interleukin‐8 Induced by Sulfur Mustard (HD) on Human Skin Cells*
Authors: Arroyo Carmen M. , Kan Robert K. , Burman Damon L. , Kahler David W. , Nelson Marian R. , Corun Charlene M. , Guzman Juanita J. , Broomfield Clarence A.
Published: December 2004

Abstract: The regulatory effects of the active form of vitamin D, 1‐α, 25‐dihydroxyvitamin D3 (1‐α, 25 (OH)2D3) were assessed on the cytokine and chemokine secretion induced by sulfur mustard on human skin fibroblasts and human epidermal keratinocytes. Stimulation of human skin fibroblasts with sulfur mustard (10−4 M for 24 hr at 37°) resulted in approximately a 5 times increase in the secretion of interleukin‐6 and over a 10 times increase for interleukin‐8, which was inhibited by 1‐α, 25 (OH)2D3, at ≤10−9 M. 1‐α, 25 (OH)2D3 also suppressed interleukin‐8 secretion by 5 times and interleukin‐6 by 4 times on sulfur mustard‐stimulated human epidermal keratinocytes at concentrations ≤ 10−9 M. The effect of 1‐α, 25 (OH)2D3 was dose‐dependent for the suppression of interleukin‐6 and interleukin‐8 induced by sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1‐α, 25 (OH)2D3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1‐α, 25 (OH)2D3 (1×10−9 M) after sulfur mustard‐stimulation (10−4 M for 24 hr at 37°C). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1×10−9 M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1‐α, 25 (OH)2D3 (2×10−9 M). 1‐α, 25(OH)2D3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory mediators and enhanced cell proliferation in human skin cells stimulated with sulfur mustard.
Tea Catechin Synergies in Inhibition of Cancer Cell Proliferation and of a Cancer Specific Cell Surface Oxidase (ECTO‐NOX)
Authors: Morré D. James , Morré Dorothy M. , Sun Howard , Cooper Raymond , Chang Joseph , Janle Elsa M.
Published: December 2004

Abstract: The anticancer properties of tea catechins are most frequently attributed to the principal catechin (‐)‐epigallocatechin‐3‐gallate (EGCg). Efficacy was evaluated using growth of cultured HeLa cells and inhibition of the enzymatic activity of a putative cell surface tea target enzyme, a cancer‐associated cell surface‐located NADH oxidase (ECTO‐NOX) designated tNOX. The amounts of EGCg required to inhibit by both criteria was reduced 10 times by combination with inactive catechins such as (‐)‐epicatechin (EC), (‐)‐epigallocatechin (EGC) or (‐)‐epicatechin‐3‐gallate (ECG). Various synthetic mixtures based on purified catechins and decaffeinated tea extracts treated enzymatically to reduce the ester bond‐containing catechins varying in EGCg content from 0.065 to 40% were of comparable efficacy to decaffeinated green tea extracts as long as EGCg was present and the ratio of total catechins to EGCg + EGC was about 1.5. Such mixtures appear to offer potential cancer protection and therapeutic advantages over those of EGCg alone through lowered toxicity of the mixture to normal cells and for more efficient blood delivery of orally‐administered catechins to a tumour site.
Sun protection offered by fabrics: on the relation between effective doses based on different action spectra
Authors: Laperre Jan , Gambichler T.
Published: December 2004

Background: Ultraviolet (UV) radiation threshold levels have been suggested by the International Commission on Non Ionising Radiation Protection (ICNIRP). The ICNIRP action spectrum differs from the action spectrum proposed by the International Commission on Illumination (CIE). Industrial hygienist employs the first approach while dermatologists and photobiologists commonly use the CIE spectrum.

Objectives: By means of the ICNIRP and CIE action spectra we aimed to calculate the ultraviolet protection factor (UPF) for clothing as a function of the UV index, and to elucidate the relation between the two action spectra.

Methods: Using a theoretically calculated solar spectrum that was determined by means of radiation transfer modelling the relation between the effective doses were assessed which were obtained by using the ICNIRP or the CIE action spectra. Employing the guidelines set out by the ICNIRP and the CIE the protection requirements for clothing were also calculated.

Results: It was found that the UPF of a textile material should be at least 2.25 times the maximum UV index observed on a cloudless day to comply with the guidelines of the CIE, or should be at least 4.13 times the maximum UV index to comply with the guidelines of the ICNIRP.

Conclusions: In Northern Europe a UPF 40 +  should indeed comply with the exposure limits (EL) proposed by the CIE or ICNIRP. However, in Southern Europe, where UV index can, as in Australia, be as high as 11 the EL can in principle be exceeded for outdoor workers or individuals staying outside the whole day. Taken into consideration the exposure geometry a clearly lower UPF seem to be sufficient in a realistic exposure situation. Nevertheless we recommend a UPF 40 + that is sufficient in extreme exposure situations in every geographical location and also resistant against UPF‐decreasing effects (‘worst case scenario’).
Photochemoprevention of skin cancer by botanical agents
Authors: F'guyer Sleem , Afaq Farrukh , Mukhtar Hasan
Published: December 2004

Photochemoprevention has become an important armamentarium in the fight against ultraviolet radiation (UVR)‐induced damage to the skin. Among many UVR‐induced damages, skin cancer is of the greatest concern as its rates have been steadily increasing in recent years and the same trend is expected to continue in the future. Ultraviolet radiation increases oxidative stress in skin cells by causing excessive generation of reactive oxygen species (ROS), leading to cancer initiation and promotion. Antioxidants have the capability to quench these ROS and much recent work shows that some of these can inhibit many UVR‐induced signal transduction pathways. Thus, identifying nontoxic strong antioxidants – capable of preventing UVR‐induced skin cancer – has become an important area of research. The use of botanical antioxidants in skin care products is growing in popularity. A wide range of such agents has been shown to prevent skin cancer in animal model systems. New agents are constantly being investigated; however, only a few have been tested for their efficacy in humans. Animal model and cell culture studies have clarified that antioxidants act by several mechanisms at various stages of skin carcinogenesis. This review focuses on skin cancer photochemopreventive effects of selected botanical antioxidants.
Seborrheic keratosis in the Korean males: causative role of sunlight
Authors: Kwon Oh S. , Hwang Eun J. , Bae Jae H. , Park Hyo E. , Lee Jong C. , Youn Jai I. , Chung Jin H.
Published: December 2004

Background/Purpose: Seborrheic keratoses (SKs) are common epidermal tumors in the white population over 40 years. The etiology of SKs is not well known; however, exposure to sunlight was suggested to play a role in the development of them. To our knowledge, no well‐designed study has been undertaken in order to investigate the clinical characteristics of SKs in a brown‐skinned Korean population. The aim of this study was to assess the prevalence and clinical features of SKs in the Korean males and to investigate the possible relationship of SKs with sun exposure and possible risk factors of developing SKs.

Methods: A total of consecutive 303 male volunteers, aged 40–70 years, were recruited from general community and public health centres. Each volunteer was interviewed regarding demographic data, sunlight sensitivity, lifetime cumulative sun exposure and smoking history. Skin examination was performed except for scalp, buttocks and genitals. All SKs were recorded about the anatomical distribution, the size of each lesion measured with a caliber, color and morphology.

Results: The mean overall prevalence of SKs in the Korean males, aged 40–70 years was 88.1%. A considerable increase in the prevalence of SKs was shown from 78.9% at 40 years to 93.9% at 50 years and 98.7% in those over 60 years. The mean number of lesions per person was 5.5 at 40 years, 9.2 at 50 years and 13.4 at 60 years. Seborrheic keratoses were considerably more frequent on exposed areas (0.47 ± 0.06/percentage of body surface area, BSA) than partly exposed areas (0.04 ± 0.01/percentage of BSA). The majority of lesions were concentrated on the face (0.98 ± 0.09/percentage of BSA) and on the dorsum of each hand (0.51 ± 0.08/percentage of BSA). The size of each lesion on exposed areas also became significantly larger by decade significantly (P < 0.01). The estimated area covered by SKs per percentage of BSA on exposed areas was 5.7‐fold larger than that on partly exposed areas at 40 years, 11.2‐fold larger at 50 years and 18.3‐fold larger at 60 years. Aging by decade showed a 2.08‐fold increased risk for SKs (n ≥ 6) (95% CI, 1.07–4.08) at 50 years and a 3.47‐fold risk (95% CI, 1.67–7.20) at 60 years on exposed areas compared with the 40‐year age group, for developing many SKs (n ≥ 6). Lifetime cumulative sunlight exposure of more than 6 h per day was associated with a 2.28‐fold higher risk of SKs than a sun exposure of less than 3 h per day. A tendency for an odds ratio value reduction was found on increasing Fitzpatrick skin types I–III to VI, V; however, this was without statistical significance.

Conclusions: Seborrheic keratoses are common in the Korean males, aged 40–70 years, and may be a major pigmentary problem. Both aging and cumulative sunlight exposure were found to be independent contributory factors.
Photosystem II protein phosphorylation follows four distinctly different regulatory patterns induced by environmental cues
Authors: PURSIHEIMO S. , MARTINSUO P. , RINTAMÄKI E. , ARO E.‐M.
Published: December 2004

Differential redox regulation of thylakoid phosphoproteins was studied in winter rye plants in vivo. The redox state of chloroplasts was modulated by growing plants under different light/temperature conditions and by transient shifts to different light/temperature regimes. Phosphorylation of PSII reaction centre proteins D1 and D2, the chlorophyll a binding protein CP43, the major chlorophyll a/b binding proteins Lhcb1 and Lhcb2 (LHCII) and the minor light‐harvesting antenna protein CP29 seem to belong to four distinct regulatory groups. Phosphorylation of D1 and D2 was directly dependent on the reduction state of the plastoquinone pool. CP43 protein phosphorylation generally followed the same pattern, but often remained phosphorylated even in darkness. Phosphorylation of CP29 occurred upon strong reduction of the plastoquinone pool, and was further enhanced by low temperatures. In vitro studies further demonstrated that CP29 phosphorylation is independent of the redox state of both the cytochrome b6/f complex and the thiol compounds. Complete phosphorylation of Lhcb1 and 2 proteins, on the contrary, required only modest reduction of the plastoquinone pool, and was subject to inhibition upon increase in the thiol redox state of the stroma. Furthermore, the reversible phosphorylation of Lhcb1 and 2 proteins appeared to be an extremely dynamic process, being rapidly modulated by short‐term fluctuations in chloroplast redox conditions.
Elevated CO2 effects on mesophyll conductance and its consequences for interpreting photosynthetic physiology
Authors: SINGSAAS E. L. , ORT D. R. , DELUCIA E. H.
Published: December 2004

Mesophyll conductance (gm) generally correlates with photosynthetic capacity, although the causal relationship between the two is unclear. The response of gm to various CO2 regimes was measured to determine its relationship to environmental changes that affect photosynthesis. The overall effect of CO2 growth environment on gm was species and experiment dependent. The data did not statistically differ from the previously shown A–gm relationship and was unaffected by CO2 treatment. The consequences of the CO2 effect on gm for interpreting photosynthesis in individual cases were investigated. Substantial effects of assumed versus calculated gm on leaf properties estimated from gas‐exchange measurements were found. This differential error resulted in an underestimation in ratio of maximum carboxylation to electron transport, especially in plants with high photosynthetic capacity. Including gm in the calculations also improved the agreement between maximum carboxylation rates and in vitro Rubisco measurements. It is concluded that gm is finite and varies with photosynthetic capacity. Including gm when calculating photosynthesis parameters from gas‐exchange data will avoid systematic errors.
Do pathways of water movement and leaf anatomical dimensions allow development of gradients in H218O between veins and the sites of evaporation within leaves?
Authors: BARBOUR M. M. , FARQUHAR G. D.
Published: December 2004

The oxygen isotope enrichment of bulk leaf water (ΔL)  is often observed to be poorly predicted by the Craig–Gordon‐type models developed for evaporative enrichment from a body of water (Δe). The discrepancy between ΔL and Δe may be explained by gradients in enrichment within the leaf as a result of convection of unenriched water to the sites of evaporation opposing the diffusion of enrichment away from the sites; a Péclet effect. However, this effect is difficult to quantify because the velocities of water movement within the leaf are unknown. This paper attempts to model the complex anatomy of a leaf, and hence such velocities, to assess if the gradients in H218O required for a significant Péclet effect between the vein and the evaporation sites are possible within a leaf. Published dimensions of cells in wheat leaves are used to calculate the cross‐sectional areas perpendicular to the flow velocities of water through assumed pathways. By combining the ratio of actual to ‘slab’ velocities with anatomical lengths, equivalent lengths (L) emerge. In this way, it is concluded that if water moves only through the cell walls, or from cell to cell via either aquaporins or plasmodesmata, and evaporates from mesophyll cells, or the substomatal cells, or from the peristomatal region (a total of 15 combinations of assumptions), then the 15 central estimates of the values of L are between 9 and 200 mm. Each of these central estimates is subject to uncertainty, but overall their magnitude is important and estimates of L are comparable with those made from fitting to isotopic data (8 mm for wheat). It is concluded that significant gradients in enrichment between the vein and the evaporation sites are likely.
Identification of microsatellite markers for a leaf rust resistance gene introgressed into common wheat from Triticum timopheevii
Authors: Leonova I. , Borner A. , Budashkina E. , Kalinina N. , Unger O. , Röuder M. , Salina E.
Published: December 2004

The tetraploid wheat Triticum timopheevii Zhuk (AtAtGG) is known as a source of genes determining resistance to many diseases. An introgressive line 842, with durable resistance to leaf rust was established by crossing T. aestivum cv. ‘Saratovskaya29’ with T. timopheevii ssp. viticulosum and used for mapping leaf rust resistance genes. Molecular analysis of the line 842 with polymorphic microsatellite markers detected introgressions of T. timopheevii into the homoeologous group 2 chromosomes of common wheat. Transloca‐tion breakpoints of introgressed fragments were localized between the markers Xgwm95 and Xgwm817 on chromosome 2A, as well as Xgwm1128 and Xgwm1067 on chromosome 2B. Linkage analysis demonstrated the association of disease resistance at the seedling stage with chromosome 2A. The gene was found to be linked with marker Xgwm817 at a genetic distance of 1.5 cM. The alien leaf rust resistance gene was temporarily designated as lrTt1.
Genetic and environmental effects on glucosinolate content and chemoprotective potency of broccoli
Authors: Farnham M. W. , Wilson P. E. , Stephenson K. K. , Fahey J. W.
Published: December 2004

Broccoli is well recognized as a source of glucosinolates and their isothiocyanate breakdown products. Glucoraphanin is one of the most abundant glucosinolates present in broccoli and its cognate isothiocyanate is sulphoraphane, a potent inducer of mammalian detoxication (phase 2) enzyme activity and anti‐cancer agent. This study was designed to measure: glucosinolate levels in broccoli florets from an array of genotypes grown in several environments; the elevation of a key phase 2 enzyme, quinone reductase, in mammalian cells exposed to floret extracts; and total broccoli head content. There were significant environmental and genotype‐by‐environment effects on levels of glucoraphanin and quinone reductase induction potential of broccoli heads; however, the effect of genotype was greater than that of environmental factors. The relative rankings among genotypes for glucoraphanin and quinone reductase induction potential changed, when expressed on a per head basis, rather than on a concentration basis. Correlations of trait means in one environment vs. means from a second were stronger for glucoraphanin and quinone reductase induction potential on a per head basis than on a fresh weight concentration basis. Results of this study indicate that development of a broccoli phenotype with a dense head and a high concentration of glucoraphanin to deliver maximum chemoprotective potential (high enzyme induction potential/glucoraphanin content) is a feasible goal.