bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of skin diseases in rural areas of Assiut Governorate, Upper Egypt
Authors: Abdel‐Hafez Kamal , Abdel‐Aty Mahmoud Attia , Hofny Eman R. M.
Published: October 2003

Background  Few epidemiological surveys have been carried out to determine the prevalence of skin diseases in the population of Egypt, particularly “Upper Egypt”. So it is a pressing necessity to conduct such a study in rural Assiut.

Objectives  To determine the prevalence of various skin diseases in rural Assiut.

Subjects and methods  A cross‐sectional community‐based survey was followed. The survey included 8008 rural inhabitants of all ages and both sexes from a representative of three villages of Assiut Governorate, Upper Egypt. The data were collected through personal interview and examination at homes from December 1994 to December 1996.

Results  They showed that 6961 (86.93%) of the studied population had one or more skin diseases. The group with parasitic skin infestations had the highest prevalence rate (27.40%) of the total sample, of which pediculosis capitis (19.37%) was the commonest. Eczema/dermatitis group had a rate of 19.82%, with pityriasis alba forming the majority (13.49%). Pigmentary disorders were 17.68%, followed by fungal skin infections (16.17%), then naevoid disorders (16.10%), hair and scalp disorders (12.07%), bacterial skin infections (10.10%), sweat gland disorders (6.16%), acne vulgaris (5.37%). Leprosy constituted 1.6/10,000. Other various skin disorders were recorded.

Conclusions  Infective‐parasitic diseases were a major problem particularly among the younger age‐group and those of low socio‐economic status.
Lepromatous leprosy and reversal reaction in a Micronesian immigrant
Authors: Ross Rustin R. , Herron Mark D. , Florell Scott R.
Published: October 2003

A 25‐year‐old Micronesian man from the island of Otia developed erythematous plaques on his legs. He was diagnosed with erythema nodosum and treated with systemic prednisone. Two months later, he presented with erythematous nodules on his forehead, cheeks, and chin (Fig. 1). Examination revealed scattered violaceous papules on his chest, arms, forearms, hands, and feet, and deep purple macules on his palms and soles. Laboratory evaluation included negative serologies for human immunodeficiency virus, rapid plasma reagin, and hepatitis A, B, and C.

Erythematous papules and nodules cover the forehead, nose, cheeks, chin, and ears

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Routine histopathology revealed nodular aggregates of histiocytes, plasma cells, and lymphocytes. Histiocytes showed basophilic clusters of organisms within vacuoles, suggesting globi. Acid‐fast stain revealed numerous acid‐fast‐positive rod‐shaped organisms. The bacterial index on the Fite stain was four (bacterial index/Ridley's logarithmic scale, indicating 10–100 bacteria/high power field) (Fig. 2). An acid‐fast stain obtained from a smear of tissue was positive for acid‐fast bacilli, but no acid‐fast bacilli were cultured.

The bacterial index on the Fite stain was four

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After the first day of treatment with dapsone 100 mg, rifampin 600 mg, and clofazimine 50 mg, the patient complained of burning and pain in his ankles and wrists. There was intense erythema within the lesions. Edema developed in his hands and feet. Consultation with the Gillis W. Long Hansen's Disease Center in Carville, Louisiana, recommended prompt treatment with corticosteroids. The edema of the hands and wrists was treated as a type I reversal reaction with prednisone 1 mg/kg/day. Subsequently, the edema and neuralgia quickly resolved in his distal extremities.
Verrucae vulgares: flashlamp‐pumped pulsed dye laser treatment in 134 patients
Authors: Kopera Daisy
Published: October 2003

Background  Various approaches have been taken in the management of verrucae vulgares, but there is still no first‐choice treatment. Thus, a study was designed to evaluate the efficacy of a flashlamp‐pumped pulsed dye laser (FPDL) in the treatment of verrucae vulgares.

Methods  Within 18 months, 134 patients with recalcitrant or untreated verrucae vulgares on their hands or feet, or in other sites, were exposed to a 585‐nm FPDL every 3.26 weeks. The following parameters were used: energy density, 8 J/cm2; spot size, 7 mm; pulse duration, 450 µs. Concomitant topical treatment was not recommended.

Results  Eight patients were lost to follow‐up. The data of 126 patients were evaluated. Up to eight laser treatments led to total remission in 62.69% of patients and partial remission in 21.42%; 9.52% did not respond to this type of management; 6.34% of patients classified the method as too painful and withdrew after the first one or two treatments. In a median follow‐up period of 5.38 months (2–16 months), one relapse occurred.

Conclusions  FPDL is safe and effective for the removal or reduction of verrucae vulgares, and requires less patient compliance compared with other treatment options.
Defence against multiple enemies
Authors: Poitrineau K. , Brown S. P. , Hochberg M. E.
Published: October 2003

Although very common under natural conditions, the consequences of multiple enemies (parasites, predators, herbivores, or even ‘chemical’ enemies like insecticides) on investment in defence has scarcely been investigated. In this paper, we present a simple model of the joint evolution of two defences targeted against two enemies. We illustrate how the respective level of each defence can be influenced by the presence of the two enemies. Furthermore, we investigate the influences of direct interference and synergy between defences. We show that, depending on certain conditions (costs, interference or synergy between defences), an increase in selection pressure by one enemy can have dramatic effects on defence against another enemy. It is generally admitted that increasing the encounter rate with a second natural enemy can decrease investment in defence against a first enemy, but our results indicate that it may sometimes favour resistance against the first enemy. Moreover, we illustrate that the global defence against one enemy can be lower when only this enemy is present: this has important implications for experimental measures of resistance, and for organisms that invade an area with less enemies or whose community of enemies is reduced. We discuss possible implications of the existence of multiple enemies for conservation biology, biological control and chemical control.
Sire coloration influences offspring survival under predation risk in the moorfrog
Authors: Sheldon B. C. , Arponen H. , Laurila A. , Crochet P.-A. , Merilä J.
Published: October 2003

When breeding, male moor frogs Rana arvalis develop a bright blue dorsal coloration which varies in intensity between males. We tested whether this colour acts as a potential signal of a male's genetic quality to female moor frogs by artificially crossing pairs of males differing in the extent of the blue coloration to the same female. Maternal half-sibships provide a powerful means to detect paternal genetic effects on offspring as they control for other potentially confounding variables. We assayed the ability of offspring to survive an ecologically realistic test of fitness by exposing them to predation by the larvae of the predatory water beetle Dytiscus marginalis. Although sire's coloration did not influence tadpole body size, it did affect their ability to survive the predation trial. Offspring of bright blue males had higher survival than those of dull males when exposed to large predators, which were more voracious predators than smaller ones. Our results indicate that paternal secondary sexual traits provide information about genetic effects on offspring fitness in this species, but suggest that these effects may be context-dependent. Variable selection caused by contextual dependence may have important consequences for the evolution of female choice rules, and for the maintenance of genetic variation for both male trait and female preference.
Multiple paternity and population genetic structure in natural populations of the poeciliid fish, Heterandria formosa
Authors: Soucy S. , Travis J.
Published: October 2003

Heterandria formosa Agassiz, exhibits internal fertilization, internal brooding of embryos, sperm storage and an extreme level of superfetation. In this study we used microsatellite markers to examine variation among seven populations that exhibited significant variance in their histories of population density. We found that the populations were genetically distinct and that the heterozygosity increased as population density increased. We also examined paternity in three of those populations and found that the number of sires per female and the number of sires per brood increased with population density. Overall, the rates of multiple paternity are quite low relative to other species. The correlations with population density suggest that contact rates play a critical role in the breeding system in this species but the low rates of multiple paternity suggest that females may exert control over fertilization of their ova.
Coevolution between hosts and parasites with partially overlapping geographic ranges
Authors: Nuismer S. L. , Thompson J. N. , Gomulkiewicz R.
Published: October 2003

Many host species interact with a specific parasite within only a fraction of their geographical range. Where host and parasite overlap geographically, selection may be reciprocal constituting a coevolutionary hot spot. Host evolution, however, may be driven primarily by selection imposed by alternative biotic or abiotic factors that occur outside such hot spots. To evaluate the importance of coevolutionary hot spots for host and parasite evolution, we analyse a spatially explicit genetic model for a host that overlaps with a parasite in only part of its geographical range. Our results show that there is a critical amount of overlap beyond which reciprocal selection leads to a coevolutionary response in the host. This critical amount of overlap depends upon the explicit spatial configuration of hot spots. When the amount of overlap exceeds this first critical level, host–parasite coevolution commonly generates stable allele frequency clines rather than oscillations. It is within this region that one of the primary predictions of the geographic mosaic theory is realized, and local maladaptation is prevalent in both species. Past a further threshold of overlap between the species oscillations do evolve, but allele frequencies in both species are spatially synchronous and local maladaptation is absent in both species. A consequence of such transitions between coevolutionary dynamics is that parasite adaptation is inversely proportional to the fraction of its host's range that it occupies. Hence, as the geographical range of a parasite increases, it becomes increasingly maladapted to the host. This suggests a novel mechanism through which the geographical range of parasites may be limited.
Age-related decline in humoral immune function in Collared Flycatchers
Authors: Cichoń M. , Sendecka J. , Gustafsson L.
Published: October 2003

Although immune function usually declines with age in humans and captive animals, little is known about whether immune function deteriorates with age in natural populations. Here we present evidence for such an age-related deterioration in humoral immune function from a wild population of the Collared Flycatcher (Ficedula albicollis). In this study, young (1-year old), mid-age (3-year old) and old (5–6-year old) females were challenged with a nonpathogenic antigen, sheep red blood cells (SRBC), while provisioning their nestlings. The level of antibodies against SRBC was measured thereafter. Old females showed markedly lower humoral immune response and produced fledglings of lower body mass in comparison with the other two age classes. Moreover, the age classes differed in the relationship between immune response and fledgling body mass with mid-age females showing a significant positive relationship while the relationship was negative but nonsignificant among young and old females. The results are discussed in light of existing theories of optimal resource allocation, ageing and the theory of terminal investment.
A molecular phylogeny of enteric bacteria and implications for a bacterial species concept
Authors: Wertz J. E. , Goldstone C. , Gordon D. M. , Riley M. A.
Published: October 2003

A molecular phylogeny for seven taxa of enteric bacteria (Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, and Serratia plymuthica) was made from multiple isolates per taxa taken from a collection of environmental enteric bacteria. Sequences from five housekeeping genes (gapA, groEL, gyrA, ompA, and pgi) and the 16s rRNA gene were used to infer individual gene trees and were concatenated to infer a composite molecular phylogeny for the species. The isolates from each taxa formed tight species clusters in the individual gene trees, suggesting the existence of ‘genotypic’ clusters that correspond to traditional species designations. These sequence data and the resulting gene trees and consensus tree provide the first data set with which to assess the utility of the recently proposed core genome hypothesis (CGH). The CGH provides a genetically based approach to applying the biological species concept to bacteria.
Sexual variation in heritability and genetic correlations of morphological traits in house sparrow (Passer domesticus)
Authors: Jensen H. , Sæther B.-E. , Ringsby T. H. , Tufto J. , Griffith S. C. , Ellegren H.
Published: October 2003

Estimates of genetic components are important for our understanding of how individual characteristics are transferred between generations. We show that the level of heritability varies between 0.12 and 0.68 in six morphological traits in house sparrows (Passer domesticus L.) in northern Norway. Positive and negative genetic correlations were present among traits, suggesting evolutionary constraints on the evolution of some of these characters. A sexual difference in the amount of heritable genetic variation was found in tarsus length, wing length, bill depth and body condition index, with generally higher heritability in females. In addition, the structure of the genetic variance-covariance matrix for the traits differed between the sexes. Genetic correlations between males and females for the morphological traits were however large and not significantly different from one, indicating that sex-specific responses to selection will be influenced by intersexual differences in selection differentials. Despite this, some traits had heritability above 0.1 in females, even after conditioning on the additive genetic covariance between sexes and the additive genetic variances in males. Moreover, a meta-analysis indicated that higher heritability in females than in males may be common in birds. Thus, this indicates sexual differences in the genetic architecture of birds. Consequently, as in house sparrows, the evolutionary responses to selection will often be larger in females than males. Hence, our results suggest that sex-specific additive genetic variances and covariances, although ignored in most studies, should be included when making predictions of evolutionary changes from standard quantitative genetic models.
Large size in an island-dwelling bird: intraspecific competition and the Dominance Hypothesis
Authors: Robinson-Wolrath S. I. , Owens I. P. F.
Published: October 2003

Differences between island- and mainland-dwelling forms provide several classic ecological puzzles. Why, for instance, are island-dwelling passerine birds consistently larger than their mainland counterparts? We examine the ‘Dominance hypothesis’, based on intraspecific competition, which states that large size in island passerines evolves through selection for success in agonistic encounters. We use the Heron Island population of Capricorn silvereyes (Zosterops lateralis chlorocephalus), a large-bodied island-dwelling race of white-eye (Zosteropidae), to test three assumptions of this hypothesis; that (i) large size is positively associated with high fitness, (ii) large size is associated with dominance, and (iii) the relationship between size and dominance is particularly pronounced under extreme intraspecific competition. Our results supported the first two of these assumptions, but provided mixed evidence on the third. On balance, we suggest that the Dominance Hypothesis is a plausible mechanism for the evolution of large size of island passerines, but urge further empirical tests on the role of intraspecific competition on oceanic islands versus that on mainlands.
Conflicting selection pressures on seed size: evolutionary ecology of fruit size in a bird-dispersed tree, Olea europaea
Authors: Alcántara J. M. , Rey P. J.
Published: October 2003

Recent evidence indicates that fruit size has evolved according to dispersers’ size. This is hypothesized to result from a balance between factors favouring large seeds and dispersers setting the maximum fruit size. This hypothesis assumes that (1) the size of fruits that can be consumed by dispersers is limited, (2) fruit and seed size are positively correlated, and (3) the result of multiple selection pressures on seed size is positive. Our studies on the seed dispersal mutualism of Olea europaea have supported the first and second assumptions, but valid tests of the third assumption are still lacking. Here we confirm the third assumption. Using multiplicative fitness components, we show that conflicting selection pressures on seed size during and after dispersal reverse the negative pattern of selection exerted by dispersers.
Temperature dependent larval resource allocation shaping adult body size in Drosophila melanogaster
Authors: Bochdanovits Z. , de Jong G.
Published: October 2003

Geographical variation in Drosophila melanogaster body size is a long-standing problem of life-history evolution. Adaptation to a cold climate invariably produces large individuals, whereas evolution in tropical regions result in small individuals. The proximate mechanism was suggested to involve thermal evolution of resource processing by the developing larvae. In this study an attempt is made to merge proximate explanations, featuring temperature sensitivity of larval resource processing, and ultimate approaches focusing on adult and pre-adult life-history traits. To address the issue of temperature dependent resource allocation to adult size vs. larval survival, feeding was stopped at several stages during the larval development. Under these conditions of food deprivation, two temperate and two tropical populations reared at high and low temperatures produced different adult body sizes coinciding with different probabilities to reach the adult stage. In all cases a phenotypic trade-off between larval survival and adult size was observed. However, the underlying pattern of larval resource allocation differed between the geographical populations. In the temperate populations larval age but not weight predicted survival. Temperate larvae did not invest accumulated resources in survival, instead they preserved larval biomass to benefit adult weight. In other words, larvae from temperate populations failed to re-allocate accumulated resources to facilitate their survival. A low percentage of the larvae survived to adulthood but produced relatively large flies. Conversely, in tropical populations larval weight but not age determined the probability to reach adulthood. Tropical larvae did not invest in adult size, but facilitated their own survival. Most larvae succeeded in pupating but then produced small adults. The underlying physiological mechanism seemed to be an evolved difference in the accessibility of glycogen reserves as a result of thermal adaptation. At low rearing temperatures and in the temperate populations, glycogen levels tended to correlate positively with adult size but negatively with pupation probability. The data presented here offer an explanation of geographical variation in body size by showing that thermal evolution of resource allocation, specifically the ability to access glycogen storage, is the proximate mechanism responsible for the life-history trade-off between larval survival and adult size.
Foundress re-emergence and fig permeability in fig tree–wasp mutualisms
Authors: Moore J. C. , Dunn A. M. , Compton S. G. , Hatcher M. J.
Published: October 2003

Some female pollinating fig wasps (foundresses) re-emerge from figs after oviposition/pollination. We investigated why this occurs in the mutualism between the gynodioecious Ficus montana and Liporrhopalum tentacularis. Re-emergence increased with foundress density in figs and some foundresses oviposited in two male figs, indicating that they re-emerge because of oviposition site limitation. Re-emergence was independent of fig diameter, indicating that permeability is not because of fig age at entry. Rather, as some foundresses also pollinate two female figs we suggest permeability is selected for because it increases pollinator production and/or efficiency (although, potentially opposing these hypotheses, we also found between-tree differences in permeability in male figs). In addition, we show that re-emergence is much more common than previously suspected, and more common from gynodioecious than monoecious fig species. We argue that our findings in F. montana could explain this pattern of incidence.
Evolution of cultural communication systems: the coevolution of cultural signals and genes encoding learning preferences
Authors: Lachlan R. F. , Feldman M. W.
Published: October 2003

In several communication systems that rely on social learning, such as bird song, and possibly human language, the range of signals that can be learned is limited by perceptual biases – predispositions – that are presumably based on genes. In this paper, we examine the coevolution of such genes with the culturally transmitted communication traits themselves, using deterministic population genetic models. We argue that examining how restrictive genetic predispositions are is a useful way of examining the evolutionary origin and maintenance of learning. Under neutral cultural evolution, where no cultural trait has any inherent advantage over another, there is selection in favour of less restrictive genes (genes that allow a wider range of signals to recognized). In contrast, cultural conformity (where the most common cultural trait is favoured) leads to selection in favour of more restrictive genes.
Association with host mitochondrial haplotypes suggests that feminizing microsporidia lack horizontal transmission
Authors: Ironside J. E. , Dunn A. M. , Rollinson D. , Smith J. E.
Published: October 2003

The amphipod crustacean Gammarus duebeni hosts two feminizing microsporidian parasites, Nosema granulosis and Microsporidium sp. Samples of G. duebeni were collected from three sites on the Scottish island of Great Cumbrae and screened for microsporidia using polymerase chain reaction. Associations between the prevalence of the two feminizing parasites and haplotypes of the host mitochondrial gene cytochrome oxidase I (COI) were investigated. The prevalence of both parasites varied significantly among the host's COI haplotypes, suggesting that horizontal transmission is rare or absent in the life cycles of the feminizing microsporidia and that all transmission must therefore be vertical. Life cycles in which all transmission is vertical are common among bacterial parasites but have never before been demonstrated in Eukaryotic parasites.
Evolutionary history of asexual hybrid loaches (Cobitis: Teleostei) inferred from phylogenetic analysis of mitochondrial DNA variation
Authors: Janko K , Kotlík P , Ráb P
Published: October 2003

Reconstruction of the evolutionary history of asexual lineages undermines their suitability as models for the studies of evolutionary consequences of sexual reproduction. Using molecular tools we addressed the origin, age and maternal ancestry of diploid and triploid asexual lineages arisen through the hybridization between spiny loaches Cobitis elongatoides, C. taenia and C. tanaitica. Reconstructions of the phylogenetic relationships among mitochondrial DNA (mtDNA) haplotypes, revealed by sequence analyses, suggest that both hybrid complexes (C. elongatoides-taenia and C. elongatoides-tanaitica) contained several asexual lineages of independent origin. Cobitis elongatoides was the exclusive maternal ancestor of all the C. elongatoides-tanaitica hybrids, whereas within the C. elongatoides-taenia complex, hybridization was reciprocal. In both complexes the low haplotype divergences were consistent with a recent origin of asexual lineages. Combined mtDNA and allozyme data suggest that the triploids arose through the incorporation of a haploid sperm genome into unreduced ova produced by diploid hybrids.
Migratory costs and contemporary evolution of reproductive allocation in male chinook salmon
Authors: Kinnison M. T. , Unwin M. J. , Quinn T. P.
Published: October 2003

Energetically demanding migrations may impact the resources available for reproductive trait development and activity, and hence favour evolution of new investment strategies for remaining resources. We conducted a large-scale experiment to evaluate the proximate cost of migration on male reproductive investment in chinook salmon (Oncorhynchus tshawytscha) and contemporary evolution of reproductive allocation. Experimentally induced differences in migratory costs (17 km inland and 17 m elevation vs. 100 km and 430 m) influenced dorsal hump size and upper jaw length, two traits influencing male mating success that are developed during migration. Longer migration also reduced tissue energy reserves available for competition and length of breeding life. Corresponding shifts in the balance between natural and sexual selection appear to have been responsible for heritable population divergence in secondary sexual trait investment, in approximately 26 generations, following colonization of spawning sites with different migratory demands.
Relationship between fluctuating asymmetry and fitness within and between stressed and unstressed populations of the wolf spider Pirata piraticus
Authors: Hendrickx F. , Maelfait J.-P. , Lens L.
Published: October 2003

Although developmental instability, measured as fluctuating asymmetry (FA), is expected to be positively related to stress and negatively to fitness, empirical evidence is often lacking or contradictory when patterns are compared at the population level. We demonstrate that two important properties of stressed populations may mask such relationships: (i) a stronger relationship between FA and fitness, resulting in stronger selection against low quality (i.e. developmental unstable) individuals and (ii) the evolution of adaptive responses to environmental stress. In an earlier study, we found female wolf spiders Pirata piraticus from metal exposed populations to be characterized by both reduced clutch masses and increased egg sizes, the latter indicating an adaptive response to stress. By studying the relationship between these two fitness related traits and levels of FA at individual level, we here show a significant negative correlation between FA and clutch mass in metal stressed populations but not in unstressed reference populations. As a result, levels of population FA may be biased downward under stressful conditions because of the selective removal of developmentally unstable (low quality) individuals. We further show that females that produced larger eggs in stressed populations exhibited lower individual FA levels. Such interaction between individual FA and fitness with stress may confound the effect of metal stress on FA, resulting in an absence of relationships between FA, fitness and stress at the population level.
Down‐regulation of anandamide hydrolase in mouse uterus by sex hormones
Authors: Maccarrone Mauro , De Felici Massimo , Bari Monica , Klinger Francesca , Siracusa Gregorio , Finazzi‐Agrò Alessandro
Published: October 2003

Endocannabinoids are an emerging class of lipid mediators, which mimic several effects of cannabinoids. Anandamide (arachidonoylethanolamide) is a major endocannabinoid, which has been shown to impair pregnancy and embryo development. The activity of anandamide is controlled by cellular uptake through a specific transporter and intracellular degradation by the enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH). We characterized FAAH in mouse uterus by radiochromatographic and immunochemical techniques, showing that the enzyme is confined to the epithelium and its activity decreases appreciably during pregnancy or pseudopregnancy because of lower gene expression at the translational level. Ovariectomy prevented the decrease in FAAH, and both progesterone and estrogen further reduced its basal levels, suggesting hormonal control of the enzyme. Anandamide was shown to induce programmed cell death in mouse blastocysts, through a pathway independent of type‐1 cannabinoid receptor. Blastocysts, however, have a specific anandamide transporter and FAAH, which scavenge this lipid. Taken together, these results provide evidence of an interplay between endocannabinoids and sex hormones in pregnancy. These findings may also be relevant for human fertility, as epithelial cells from healthy human uterus showed FAAH activity and expression, which in adenocarcinoma cells was increased fivefold.
The cationic C‐terminus of rat Muc2 facilitates dimer formation post translationally and is subsequently removed by furin
Authors: Xu Gongqiao , Bell Sherilyn L. , McCool Dorothy , Forstner Janet F.
Published: October 2003

Earlier immunolocalization experiments showed that the extreme cationic C‐terminus of the rat intestinal mucin Muc2 (RMC) was present at the base of intestinal goblet cells in the vicinity of ER and golgi compartments, but was not found with the rest of the mucin in apical storage granules. This prompted us to investigate the possibility that an early proteolytic cleavage reaction occurs post‐translationally. A plasmid pRMC, encoding the C‐terminal 534 amino acids of the mucin, was expressed in COS‐7 cells and was shown to undergo cleavage at an R‐T‐R‐R sequence located within the C‐terminal 14 amino acids. Cleavage did not occur with the construct RMCfH, a furin site‐mutated (A‐T‐A‐A) counterpart of pRMCH (poly His6 tagged RMC). Addition of a furin inhibitor to COS‐7 cell incubations also prevented cleavage of RMC and RMCH products. 35S pulse‐chase kinetic experiments revealed that a truncated mutant lacking the C‐terminal 14 amino acids (pRMCΔCT) forms faulty (doublet) dimers in the ER. These were not secreted as efficiently as the normal dimer of wild‐type (pRMC) constructs. Thus the cationic C‐terminus of rMuc2 apppears to facilitate the correct formation of normal Muc2 domain dimers.
Detection and distribution patterns of telomerase activity in insects
Authors: Sasaki Takashi , Fujiwara Haruhiko
Published: October 2003

Telomeres of most insects consist of pentanucleotide (TTAGG)n repeats, although the repeats are absent in Diptera and some other insect species, where the telomere regions are perhaps maintained without telomerase. To understand various and unusual telomere formation in insects, we have studied the characteristic features of a putative insect telomerase that has not been previously described. Using a modified telomeric repeat amplification protocol (TRAP), we first detected the telomerase activity in crickets, cockroaches and two Lepidopteran insects. The telomerase from crickets and cockroaches required dATP, dGTP and dTTP but not dCTP as a substrate and sequence analyses of the products of TRAP revealed that the (TTAGG)n repeats are synthesized by telomerase. The cockroach telomerase was detected both in somatic (fat body, muscle and neural tissues) and germ line (testis) cells, suggesting that expression of this enzyme is not regulated in a tissue‐specific manner at an adult stage. While we detected high levels of telomerase activity in crickets and cockroaches, we could not detect activity in all tissues and cell cultures of the silkworm, Bombyx mori and in two Drosophila and one Sarcophaga cell lines. This supports the theory that Dipteran insects maintain their telomeres without telomerase.
Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity
Authors: Seydel Ulrich , Oikawa Masato , Fukase Koichi , Kusumoto Shoichi , Brandenburg Klaus
Published: October 2003

Lipopolysaccharides (LPS, endotoxin) represent a major virulence factor of Gram‐negative bacteria, which can cause septic shock in mammals, including man. The lipid anchor of LPS to the bacterial outer membrane, lipid A, exhibits a peculiar chemical structure, harbours the ‘endotoxic principle’ of LPS and is also responsible for the expression of pathophysiological effects. Chemically modified lipid A can be endotoxically inactive, but may express strong antagonistic activity against endotoxically active LPS. By applying orientation measurements with attenuated total reflectance (ATR) infrared spectroscopy on hydrated lipid A samples, we show here that these different biological activities are directly correlated to the intrinsic conformation of lipid A. Bisphosphoryl‐hexaacyl lipid A molecules with an asymmetric (4/2) distribution of the acyl chains linked to the diglucosamine backbone have a large tilt angle (> 45 °) of the diglucosamine backbone with respect to the membrane surface, a conical molecular shape (larger cross‐section of the hydrophobic than the hydrophilic moiety), and are endotoxically highly active. Monophosphoryl hexaacyl lipid A has a smaller tilt angle, and the conical shape is less expressed in favour of a more cylindrical shape. This correlates with decreasing endotoxic activity. Penta‐ and tetraacyl lipid A or hexaacyl lipid A with a symmetric acyl chain distribution (3/3) have a small tilt angle (< 25 °) and a cylindrical shape and are endotoxically inactive, but may be antagonistic.
Secondary structure composition of reconstituted subunit b of the Escherichia coli ATP synthase
Authors: Greie Jörg‐Christian , Deckers‐Hebestreit Gabriele , Altendorf Karlheinz
Published: October 2003

Subunit b of the Escherichia coli ATP synthase was isolated by preparative gel electrophoresis, acetone precipitated and after ion‐pair extraction redissolved in a buffer either containing n‐dodecyl‐β‐d‐maltoside or sodium cholate. The secondary structure of isolated subunit b was shown to be the same as within the FO complex, but was strongly dependent on the detergent used for replacement of the phospholipid environment. This was shown by an identical tryptic digestion pattern, which was strongly influenced by the detergent used for solubilization. An influence of the detergent n‐dodecyl‐β‐d‐maltoside on the secondary structure of the hydrophilic part of subunit b was also shown for the soluble part of the polypeptide comprising residues Val25 to Leu156 (bsol) using CD spectroscopy. In order to determine the secondary structure of subunit b in its native conformation, isolated subunit b was reconstituted into E. coli lipid vesicles and analyzed with CD spectroscopy. The resulting spectrum revealed a secondary structure composition of 80% α helix together with 14% β turn conformation. These results suggest that subunit b is not a rigid rod‐like α helix simply linking F1 to FO, but rather provides an inherent flexibility for the storage of elastic energy within the second stalk generated by rotational movements within the F1FO complex.
Ser/Thr phosphorylation of hematopoietic specific protein 1 (HS1)
Authors: Ruzzene Maria , Brunati Anna M. , Sarno Stefania , Marin Oriano , Donella‐Deana Arianna , Pinna Lorenzo A.
Published: October 2003

Hematopoietic lineage cell‐specific protein 1 (HS1), a tyrosine multiphosphorylated protein implicated in receptor‐mediated apoptosis and proliferative responses, is shown here to become Ser/Thr phosphorylated upon incubation of platelets with radiolabeled inorganic phosphate. The in vivo Ser/Thr phosphorylation of HS1 is enhanced by okadaic acid and reduced by specific inhibitors of casein kinase (CK)2. In vitro, HS1 is an excellent substrate for either CK2 α subunit alone (Km = 47 nm) or CK2 holoenzyme, tested in the presence of polylysine (Km = 400 nm). Phosphorylation reaches a stoichiometry of about 2 mol phosphate per mol HS1 and occurs mainly at threonyl residue(s), mostly located in the N‐terminal region, but also at seryl residue(s) residing in the central core of the molecule (208–402), as judged from experiments with deleted forms of HS1.

 Ser/Thr phosphorylation of HS1, either induced in vivo by okadaic acid or catalysed in vitro by CK2, potentiates subsequent phosphorylation at tyrosyl residues. These data indicate the possibility that regulation of HS1 may also be under the control of Ser/Thr phosphorylation, and suggest that in quiescent cells CK2 could play a role in inducing constitutive Tyr phosphorylation of HS1 in the absence of stimuli that activate the protein tyrosine kinase pathway.
Ligand‐binding properties and structural characterization of a novel rat odorant‐binding protein variant
Authors: Briand Loïc , Nespoulous Claude , Perez Valérie , Rémy Jean‐Jacques , Huet Jean‐Claude , Pernollet Jean‐Claude
Published: October 2003

After characterization of a novel odorant‐binding protein (OBP) variant isolated from the rat nasal mucus, the corresponding cDNA was cloned by RT‐PCR. Recombinant OBP‐1F, the sequence of which is close to that of previously reported rat OBP‐1, has been secreted by the yeast Pichia pastoris at a concentration of 80 mg·L−1 in a form identical to the natural protein as shown by MS, N‐terminal sequencing and CD. We observed that, in contrast with porcine OBP‐1, purified recombinant OBP‐1F is a homodimer exhibiting two disulfide bonds (C44–C48 and C63–C155), a pairing close to that of hamster aphrodisin. OBP‐1F interacts with fluorescent probe 1‐aminoanthracene (1‐AMA) with a dissociation constant of 0.6 ± 0.3 µm. Fluorescence experiments revealed that 1‐AMA was displaced efficiently by molecules including usual solvents such as EtOH and dimethylsulfoxide. Owing to the large OBP‐1F amounts expressed, we set up a novel biomimetic assay (volatile‐odorant binding assay) to study the uptake of airborne odorants without radiolabelling and attempted to understand the odorant capture by OBP in the nasal mucus under natural conditions. The assay permitted observations on the binding of airborne odorants of different chemical structures and odors (2‐isobutyl‐3‐methoxypyrazine, linalool, isoamyl acetate, 1‐octanal, 1‐octanol, dimethyl disulfide and methyl thiobutyrate). Uptake of airborne odorants in nearly physiological conditions strengthens the role of OBP as volatile hydrophobic odorant carriers in the mucus of the olfactory epithelium through the aqueous barrier towards the chemo‐sensory cells.
High yield purification and physico‐chemical properties of full‐length recombinant allelic variants of sheep prion protein linked to scrapie susceptibility
Authors: Rezaei Human , Marc Daniel , Choiset Yvan , Takahashi Masayuki , Hui Bon Hoa Gaston , Haertlé Thomas , Grosclaude Jeanne , Debey Pascale
Published: October 2003

Sheep susceptibility to scrapie is governed by polymorphisms at two major sites, codons 136 and 171, of the prp gene. To get more insight into the prion protein (PrP) sequence‐linked basis of differential scrapie susceptibility, a high yield one‐step method for the purification (over 99% final purity) of the full‐length recombinant sheep PrP was developed, based on the affinity of the conserved octapeptide repeats for transition‐metal cations. Thermal and chemical denaturation experiments and limited proteolysis studies were performed on the natural variants (A136R171, V136Q171 and A136Q171) and a recombinant PrP mutated at position 136 (V136R171). Results revealed the influence of mutations in positions 136 and 171 on the folding thermodynamic parameters and on the conformation of the C‐terminal domain. Together, our results show that the VQ cellular protein linked to higher scrapie susceptibility is intrinsically more compact and/or stable than the resistance‐linked AR counterpart. This might lead to a lower in vivo clearance rate of VQ and a consequently higher probability of occurrence of pathological events.
Melanom‐Stroma‐Interaktionen und ihre Bedeutung für die Melanomprogression
Authors: Ruiter Dirk J. , Herlyn Meenhard
Published: October 2003

Das Melanom der Haut ist ein aggressiv wachsender Tumor, der frühzeitig metastasieren kann. Nicht nur die Melanomzellen selbst, sondern auch das tumorumgebende Mikroenvironment spielt bei der Entstehung und der Progression des Melanoms eine wichtige Rolle. In diesem Mini‐Review werden die strukturellen und funktionellen Aspekte der Interaktion von Melanomzellen und umgebendem Stroma dargestellt, sowie deren klinische Relevanz diskutiert.
Sentinel‐Lymphonodektomie beim malignen Melanom – ein Update
Authors: Kretschmer Lutz , Bertsch Hans Peter , Meller Johannes
Published: October 2003

Zehn Jahre nach der Einführung des Sentinel‐Konzeptes in die Behandlungsstrategie des malignen Melanoms gilt es Bilanz zu ziehen. Die komplexe Methode hat sich als hinreichend sensitiv erwiesen, auch wenn bei der histologischen Aufarbeitung ein bestimmter Prozentsatz falsch‐negativer Resultate in Kauf genommen werden muß. Es wird weiterhin kontrovers diskutiert, ob die generelle Durchführung der Sentinel‐Lymphonodektomie bei High‐Risk‐Patienten gerechtfertigt ist. Drei prospektive Studien zur elektiven Lymphknotendissektion konnten nicht beweisen, daß eine Früherkennung und Frühtherapie von Lymphknotenmetastasen zu einem Überlebensvorteil führt. Dagegen fand eine retrospektive Multizenterstudie ein verbessertes Overall‐Survival für Patienten mit histologisch positivem Sentinel, im Vergleich zu Patienten, bei denen klinisch vergrößerte Lymphknotenmetastasen erst im weiteren Verlauf exzidiert wurden. Der pathologische Status des Sentinel‐Lymphknotens gilt heute als unabhängiger Prognosefaktor. Wie jedes invasive Staging‐Verfahren verlangt auch die Sentinel‐Lymphonodektomie nach einer therapeutischen Konsequenz. Leider existiert derzeit keine allgemein anerkannte adjuvante Therapie. Auch ist bislang nicht gezeigt worden, daß Patienten mit positivem Sentinel von einer komplettierenden regionalen Lymphknotendissektion profitieren.
Bexarotene – an alternative therapy for progressive cutaneous T‐cell lymphoma? First experiences
Authors: Bohmeyer J. , Stadler R. , Kremer A. , Nashan D. , Muche M. , Gellrich S. , Luger T. , Sterry W.
Published: October 2003

Background: A standard therapy for advanced cutaneous T‐cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor‐specific retinoid that has been approved for systemic second‐line therapy for cutaneous T‐cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T‐cell lymphomas, a pilot trial was initiated.

Patients and methods: In a pilot project 10 patients with advanced cutaneous T‐cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i. e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly.

Results: In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events.

Conclusion: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.
Die solare Keratose: Von der Präkanzerose zum präinvasiven Plattenepithelkarzinom – Therapeutischer Ansatz nach dem Bioinduktionsverfahren
Authors: Oster‐Schmidt Claus , Altmeyer Peter , Stücker Markus
Published: October 2003

Hintergrund: Solare Keratosen sind präkanzeröse Veränderungen chronisch UV‐geschädigter Haut, die histologisch dem präinvasiven Stadium eines Plattenepithelkarzinoms entsprechen. Als solche stellen sie eine unbedingt behandlungsbedürftige Hauterkrankung dar, um eine Progression in das invasive Stadium zu verhindern. Therapeutisch kommen sowohl medikamentöse als auch physikalisch‐ablative Methoden in Frage. Hier wird über einen neuartigen Ansatz, die Bioinduktionstherapie mit Imiquimod‐5 %‐Creme, berichtet.

Patienten und Methodik: In einer prospektiven Fallserie wurden 7 Patienten mit solaren Keratosen mit Imiquimod‐5 %‐Creme behandelt. Die Creme wurde an 5 Tagen/Woche über zwei Wochen appliziert. Der Therapieerfolg wurde nach Ende der Behandlung in regelmäßigen Abständen, zum Teil auch histologisch, weiter kontrolliert. Ein weiterer unbehandelter Patient wurde als Kontrolle mitgeführt.

Ergebnisse: Bei 6 der 7 behandelten Patienten heilten die solaren Keratosen vollständig ab, ein Patient reagierte nicht auf die Therapie. Bei den Patienten traten durchschnittlich 2 Jahre nach Therapieende keine weiteren solaren Keratosen auf. Bei dem Kontrollpatienten heilte die Keratose spontan ab. Als unerwünschte Wirkungen fanden sich unter Therapie Erythem, Ödem und Erosion in unterschiedlicher Ausprägung. Diese bildeten sich komplett zurück.

Schlußfolgerungen: Das Konzept der Bioinduktionstherapie mit Imiquimod‐5 %‐Creme stellt einen vielversprechenden Ansatz in der Behandlung von kutanen Präkanzerosen wie der solaren Keratose dar.
Part one: Restoring patients to health—Outcomes and indicators of advanced nursing practice in adult critical care
Authors: Ball Carol , Cox Carol L
Published: October 2003

The key characteristics of advanced nursing practice have been a subject of international debate over the past decade. To address this debate, a grounded theory study was undertaken by one of the authors which sought to identify the key characteristics of advanced nursing practice in adult critical care. The outcome of the main study was a theory of legitimate influence in which enhancing patient stay and improving patient outcome represented the dual purpose of advanced nursing practice in critical care. Fundamental to these factors is strategic activity. This encompasses improving patient care, facilitating continuity of care and engaging in patient education. The outcome of these strategic activities can be evaluated through evidence of eased transition across complex hospital networks, patient satisfaction and enabling of independence. The findings reflect a change in the focus and delivery of care to the critically ill and their relatives by nurses practising at an advanced level. In the second paper of this series, the intervening conditions that affect the expression of legitimate influence will be discussed.
The parenting competency framework: Learning to be a parent of a child with asthma
Authors: Maltby Hendrika J , Kristjanson Linda , Coleman Mardhie E
Published: October 2003

Every parent who faces an illness in their child might doubt their competence to care. When a chronic illness is diagnosed, competence can be severely challenged because of the sustained and multiple disruptions to daily life. A conceptual framework entitled ‘Learning to be a Parent of a Child with Asthma’ was developed from the results of a descriptive phenomenological study completed in Perth, Western Australia. It describes the stages of challenges to competency that parents experience as they learn to care for their asthmatic children. The impact of this illness on parents and the extent to which they are able to help their children respond to the demands of asthma are critical components in understanding the effect of this disease on parental competency. Insight into parental competency and the relationship to chronic illness will help health professionals provide the support and information needed by parents to manage asthma in their children.