bluuebunny/crossref_metadata_2025 huggingface dataset:
Stop female genital mutilation: appeal to the international dermatologic community
Authors: Morrone Aldo , Hercogova Jana , Lotti Torello
Published: March 2003

Female genital mutilation (FGM) is a traditional cultural practice, but also a form of violence against girls, which affects their lives as adult women. FGM comprises a wide range of procedures: the excision of the prepuce; the partial or total excision of the clitoris (clitoridectomy) and labia; or the stitching and narrowing of the vaginal orifice (infibulation).

The number of girls and women who have been subjected to FGM is estimated at around 137 million worldwide and 2 million girls per year are considered at risk. Most females who have undergone mutilation live in 28 African countries.

Globalization and international migration have brought an increased presence of circumcised women in Europe and developed countries. Healthcare specialists need to be made aware and trained in the physical, psychosexual, and cultural aspects and effects of FGM and in the response to the needs of genitally mutilated women. Health education programs targeted at immigrant communities should include information on sexuality, FGM, and reproduction. Moreover, healthcare workers should both discourage women from performing FGM on their daughters and receive information on codes of conduct and existing laws. The aim is the total eradication of all forms of FGM.
Childhood lichen planus: a study of 87 cases
Authors: Handa Sanjeev , Sahoo Bijaylaxmi
Published: March 2003

Aims We undertook this study to analyze the clinical profile of childhood lichen planus (LP) prevailing in north India, and to highlight differences from and similarities with adult LP.

Methods Clinical records of children with LP, who attended the Pediatric Dermatology Clinic, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, India, from July 1988 to December 2000, were analyzed.

Results Eighty‐seven patients with LP were examined during a 12.5‐year period of observation. These patients formed 2.5% of the total number of pediatric dermatology patients and 0.6% of the total number of new dermatology outpatients. The male : female ratio was 1.1 : 1. The age at onset was between 8 months and 12 years (mean, 7.1 years). Classical LP was observed in 53 (60.9%) patients, followed by actinic LP in 10 (11.5%), and lichen planus hypertrophicus (LPH) and linear LP in eight (9.2%) each. Other forms seen were eruptive, follicular, lichen planopilaris, atrophic, and bullous LP. The involvement of skin alone was observed in 75 (86.2%) children and mucosa alone only in one (1.1%) child. Concomitant skin and mucosal involvement was seen at the time of presentation in four patients, while mucosal involvement occurred later during the course of the disease in seven patients. Lesions appeared earlier in boys than in girls.

Conclusions The natural history of LP in children was essentially similar to that in adults. Unusual features, such as involvement of the palms and soles and upper eyelids, were observed. Actinic LP, mimicking melasma, as reported in adult women, also seems to occur in children.
An interesting case of colocalization of segmental lichen planus and vitiligo in a 14‐year‐old boy
Authors: Sardana Kabir , Sharma Ravi C. , Koranne R. V. , Mahajan Supriya
Published: March 2003

A 14‐year‐old boy had segmental vitiligo (L3−4) on the right thigh and leg for 4 years, and was advised to apply topical clobetasol propionate, 0.05%, in the night, with daily sun exposure for 10 min, as he refused to comply with topical psoralens. As there was no response to therapy even after 3 months, the patient stopped the steroid cream but continued with the sun exposure. Subsequently, the patient noticed gradual‐onset, itchy, violaceous, pigmented, raised lesions superimposed on the vitiligo macules. Cutaneous examination revealed violaceous, polygonal papules, 0.5 × 0.5 cm in size, some of which coalesced to form discrete violaceous plaques, confined to areas of vitiligo, with a clear‐cut demarcation from normal skin (Fig. 1). The scalp, palms, soles, nails, and mucosa were normal. Histopathology of the polygonal papules revealed hyperkeratosis, wedge‐shaped hypergranulosis, irregular acanthosis with saw toothing of the rete ridges, basal cell liquefaction, and a band‐like lymphocytic infiltrate (Fig. 2), consistent with lichen planus. The patient was subsequently prescribed fluticasone propionate (0.05%) ointment once daily for the lesions of lichen planus. There was a marked improvement in the lesions of lichen planus after 1 month.

Violaceous papules of lichen planus colocalized on vitiligo macules with associated leukotrichia seen on the right leg

image

Histopathology reveals hyperkeratosis, wedge‐shaped hypergranulosis, irregular acanthosis with saw toothing of the rete ridges, basal cell liquefaction, and a band‐like lymphocytic infiltrate (hematoxylin and eosin, × 40)

image
Polymyositis and dermatomyositis associated with malignancy: a 30‐year retrospective study
Authors: Wakata Nobuo , Kurihara Teruyuki , Saito Eizo , Kinoshita Masao
Published: March 2003

Background Polymyositis and dermatomyositis in association with malignancy are paraneoplastic syndromes, but the incidence, treatment and factors that predict associated cancer and its prognosis all remain unclear.

Patients and Method During the 30‐year period 1969–99, we treated 64 patients who had polymyositis (including two with cancer) and 28 patients who had dermatomyositis (including 10 with cancer). We compared the clinical findings of the patients who had cancer with the findings of those who did not have cancer.

Results The risk of cancer is significantly higher in dermatomyositis and somewhat higher in polymyositis. An increased cancer risk was found in male patients with dermatomyositis who were older than 50 years. Cancer was diagnosed within 4 years before or after the diagnosis of polymyositis or dermatomyositis, and usually within 1 year. An operation was not possible in many of the patients with cancer because of the advanced stage of the disease.

Conclusion Our findings suggest that early discovery of malignancy is critical in cases of polymyositis and dermatomyositis.
Peptides with indirect in vivo activity against an intracellular pathogen: selective lysis of infected macrophages
Authors: Yokum T.S. , Hammer R.P. , McLaughlin Mark L. , Elzer Philip. H.
Published: March 2003

Abstract: A collection of natural peptides, simplified analogs of natural peptides, de novo amphipathic peptides and de novo amphipathic peptides composed of 50–80% α,α‐dialkylated glycines (α,α‐Dags) were synthesized on solid‐phase resin as the C‐terminus amides using N‐α‐fluorenylmethyloxycarbonyl protection. The synthesis of the peptides rich in α,α‐Dags used acid fluoride coupling methods. The peptides show antimicrobial activity against Escherichia coli and Staphylococcus aureus but no direct antimicrobial activity against Brucella abortus at 100 µmin vitro. However, in vivo treatment with several of these peptides results in significant reductions of B. abortus in chronically infected immune BALB/c mice relative to infected control animals. The chronically infected mice were susceptible to peptide toxicity at much lower peptide doses than control animals. The highest nonlethal dose for infected mice was only 25 µg for melittin, whereas 500 µg doses were nonlethal for many of the other peptides. Several of the α,α‐Dag‐rich peptides selectively destroy B. abortus‐infected murine macrophages in vitro. Thus, these peptides apparently reduce the bacterial load in vivo by destroying a portion of the infected macrophages and exposing the sequestered bacteria to the immune response in the mice.
Microsatellite assessment of multiple paternity in natural populations of a live-bearing fish, Gambusia holbrooki
Authors: Zane  , Nelson  , Jones  , Avise
Published: March 2003

Three polymorphic microsatellite loci were isolated and employed to examine paternity patterns in two natural populations of live-bearing mosquitofish, Gambusia holbrooki. Each locus displayed four to five alleles per population in samples of presumably unrelated adults. Nearly 900 embryos from a total of 50 pregnant females were assayed individually, and paternal alleles in each embryo were identified. Counts of paternal alleles, Mendelian segregation patterns, multilocus allelic associations and genetic relatedness coefficients were employed to estimate the minimum and effective numbers of fathers per brood. At least 90% of the assayed broods were shown to have been fathered by multiple males, a figure substantially higher than previous estimates based on less polymorphic genetic loci. However, the genetic data yield a face-value estimate of only about 2.2 fathers per brood, a number that seems perhaps surprisingly low based on frequencies of attempted copulations by males. Both biological and sampling factors that might bias mean sire counts downward are considered. Although higher sire counts per brood might be obtained from loci with even greater numbers of alleles, little statistical room remains for higher frequency estimates of multiple paternity in Gambusia.
The costs of sex due to deleterious intracellular parasites
Authors: Hastings
Published: March 2003

A major problem in evolutionary theory is to explain the widespread occurrence of sexual recombination. This is particularly difficult in anisogamous species where the familiar ‘two-fold cost of sex’ is encountered. Another cost has recently been identified: that fusion of gametes allows intracellular parasites or deleterious ‘selfish’ genomes to invade a population. These costs of anisogamy and the ability of cytoplasmic agents to invade a sexual population are quantified, allowing the costs and consequences of different modes of reproduction to be compared. It is found that the costs of selfish elements are likely to be very high and, in particular, that isogamous sexual reproduction (the putative ‘primitive’ form) is not cost-free, but incurs a fitness reduction of the order of 90%; thus a large selective disadvantage occurs in the initial evolution of sex which is ignored in standard analysis. Even once anisogamy has evolved, the low levels of ‘paternal leakage’ observed in many extant organisms may allow selfish cytoplasmic elements to spread, resulting in moderate to large decreases in host population fitness. However, much of the cost of selfish elements is avoided in sexual lifecycles with a large number of asexual cellular divisions between sexual reproduction: this greatly impedes the spread of selfish agents and reduces the fitness loss attributable to selfish elements.
Evidence for effects of restorer genes on male and female reproductive functions of hermaphrodites in the gynodioecious species Thymus vulgaris L.
Authors: Gigord  , Lavigne  , Shykoff  , Atlan
Published: March 2003

In Thymus vulgaris L., sex determination involves both the nuclear and the cytoplasmic genomes: the cytoplasm is responsible for male-sterility (the female phenotype) while specific nuclear genes may restore male fertility (the hermaphrodite phenotype). Previous observations have shown high variation among hermaphrodites for pollen and seed production. In order to investigate the origin of this variation, 12 female plants, four from each of three populations, were hand-pollinated with pollen from hermaphrodites from three different paternal populations. The sex-ratio (i.e. the frequency of hermaphrodites) produced and the reproductive functions of these offspring were measured. A strong positive correlation was observed between the sex-ratio within a family and both female and male reproductive functions of its hermaphrodites. No such correlation was found for females. This result suggests that restorer genes may be directly or indirectly involved both in sex determination and in the efficiency of resource allocation to reproductive functions. As a consequence, female advantage, i.e. the relative fecundity of females to hermaphrodites, is larger in families with low sex-ratio, and this might affect the evolution of this gynodioecious breeding system.
Accuracy and power in fluctuating asymmetry studies: effects of sample size and number of within-subject repeats
Authors: Dongen S. Van
Published: March 2003

This paper presents results from simulations investigating the effect of sample size, number of within-subject repeats and relative degree of measurement error on the power and accuracy of test for fluctuating asymmetry (FA). These data confirm that sampling variation of population-level FA-estimates is large and that high sample size is required to obtain reasonably high power when testing for FA or comparing FA levels between populations. The results also clearly show that increasing the number of within-subject repeats can dramatically increase accuracy and power when measurement error is relatively high.
A long-term study on interactions between the Adh and αGpdh allozyme polymorphisms and the chromosomal inversion In(2L)t in a seminatural population of D. melanogaster
Authors: Kamping  , Delden W. Van
Published: March 2003

The Adh and αGpdh allozyme loci (both located on the second chromosome) showed considerable fluctuations in allele frequencies in a seminatural population of Drosophila melanogaster during 1972–97. Both long-term and short-term fluctuations were observed. The short-term fluctuations occurred within almost all years and comparison of allele frequencies between winters and summers showed significantly higher AdhS (P < 0.001) and αGpdhF (P < 0.01) allele frequencies in summers. Frequencies of these alleles were significantly positively correlated with environmental temperature, suggesting the adaptive significance of these allozyme polymorphisms. Frequency changes of the Odh locus (located on the third chromosome) showed no seasonal pattern and were not correlated with environmental temperature. Almost all short-term and long-term increases in AdhS frequency were accompanied by a corresponding decrease in αGpdhS frequency (r = –0.82, P < 0.001) and vice versa. Further analysis showed that gametic disequilibria between the Adh and αGpdh loci, which frequently occurred, were due to the presence of inversion In(2L)t located on the same chromosome arm and In(2L)t frequencies were positively correlated with environmental temperature. Gametic disequilibria between Adh and Odh and between Odh and αGpdh were hardly observed. Because In(2L)t is exclusively associated with the AdhS/αGpdhF allele combination, the observed correlated response in Adh/αGpdh allele frequencies is (at least partly) explained by hitchhiking effects with In(2L)t. This means that the adaptive value of the allozyme polymorphisms has been overestimated by ignoring In(2L)t polymorphism. Fluctuations in Adh allele frequencies are fully explained by selection on In(2L)t polymorphism, whereas we have shown that αGpdh frequency fluctuations are only partly explained by chromosomal hitchhiking, indicating the presence of selective differences among αGpdh genotypes in relation with temperature and independent of In(2L)t. Frequency fluctuations of αGpdh and In(2L)t are consistent with their latitudinal distributions, assuming that temperature is the main environmental factor varying with latitude that causes directly or indirectly these frequency distributions. However, the results of the tropical greenhouse population show no correlation of Adh (independent of In(2L)t) and Odh allele frequencies with environmental temperature, which may indicate that the latitudinal distribution in allele frequencies for these loci is not the result of selection on the F/S polymorphism in a direct way.
Mate recognition systems in a species flock of Mexican pupfish
Authors: Strecker U. , Kodric-Brown A.
Published: March 2003

The pupfishes of Lake Chichancanab (Mexico) provide a unique opportunity to study the evolution of premating reproductive barriers. This group of endemic species is of recent origin and the lineages differ in morphological traits indicating trophic specialization, but show very little genetic change. We studied the function of visual and chemical cues in the mate recognition system of three morphospecies, Cyprinodon beltrani, C. labiosus and C. maya. Only in C. maya, which is genetically the most distinct member of the group, do females show the ability to identify males of their own type, both visually and chemically. C. labiosus females discriminated between their own and C.  beltrani males based on chemical but not visual cues. C. beltrani, which is morphologically the least differentiated member of the group, showed no interspecific mate recognition. Females responded more strongly to the visual and chemical cues of their own males than to their own females, but they did not discriminate between their own males and those of the other two morphospecies based upon either type of cue. These results suggest that different levels of behavioural isolation have been established: most isolated is C. maya, and the least is C. beltrani. C. labiosus has an intermediate position. The results also suggest that species recognition cues based on different sensory modalities do not necessarily evolve together, and may evolve at different rates.
What does the male function hypothesis claim?
Authors: Burd  , Callahan
Published: March 2003

Paternal, rather than maternal, fitness consequences of reproductive traits are the lynchpin in many hypotheses about reproductive evolution in hermaphroditic angiosperms. These hypotheses often differ in their predictions, so that supporting or contradictory evidence for one hypothesis may not reflect similarly on another, even though both may be referred to as ‘the male function hypothesis’. We provide graphical representations of four male function hypotheses from the recent literature in order to highlight their differences. We offer and explain two recommendations to reduce ambiguity in terminology: (1) male function hypotheses should address the evolution of excess flowers per se, rather than total flower number, which is usually highly plastic in modular organisms with open growth form; and (2) attention must be given to whole plant fitness, rather than fitness per flower or per inflorescence. In empirical studies, we recommend the use of path analysis to dissect the multiple pathways (through both male and female function) by which selection may act on excess flower number.
Local adaptation of a holoparasitic plant, Cuscuta europaea: variation among populations
Authors: Koskela  , Salonen  , Mutikainen
Published: March 2003

Locally adapted parasites have higher infectivity and/or fitness on sympatric than on allopatric hosts. We tested local adaptation of a holoparasitic plant, Cuscuta europaea, to its host plant, Urtica dioica. We infected hosts from five sites with holoparasites from the same five sites and measured local adaptation in terms of infectivity and parasite performance (biomass) in a reciprocal cross-infection experiment. The virulence of the parasite did not differ between sympatric and allopatric hosts. Overall, parasites had higher infectivity on sympatric hosts but infectivity and parasite performance varied among populations. Parasites from one of the populations showed local adaptation in terms of performance, whereas parasites from one of the populations had higher infectivity on allopatric hosts compared with sympatric hosts. This among-population variation may be explained by random variation in parasite adaptation to host populations or by time-lagged co-evolutionary oscillations that lead to fluctuations in the level of local adaptation.
Temperature and clinal variation in larval growth efficiency in Drosophila melanogaster
Authors: Robinson S. J. W. , Partridge L.
Published: March 2003

Geographic clines in ectotherm species including Drosophila melanogaster have been found throughout the world, with genetically larger body size and shorter development time occurring at high latitudes. Temperature is thought to play a major role in the evolution of this clinal variation. Laboratory thermal selection has effects similar to those seen in geographical clines. Evolution at low temperatures results in more rapid development to larger adult flies. This study investigated the effects of geographical origin and experimental temperature on larval growth efficiency in D. melanogaster. Larvae from populations that had evolved at high latitudes were found to use limited food more efficiently, so that the overall adult body size achieved was larger. Larvae reared at a lower experimental temperature (18 °C) used food more efficiently than those reared at a higher temperature (25 °C). The increases in growth efficiency found in populations from high latitudes could explain their increased body size and more rapid development.
The interplay between colonization history and gene flow in passively dispersing zooplankton: microsatellite analysis of rotifer resting egg banks
Authors: Gómez A. , Adcock G. J. , Lunt D. H. , Carvalho G. R.
Published: March 2003

Zooplanktonic organisms that disperse passively as diapausing eggs often exhibit surprisingly strong population subdivision given their high colonization ability. Here we attempt to disentangle the impacts of colonization history and gene flow on these organisms by studying the population genetic structure of the rotifer Brachionus plicatilis. The resting egg banks of B. plicatilis in fourteen salt lake populations in the Iberian Peninsula were examined using seven microsatellite loci. A remarkably high degree of geographical structuring was found (Fst=0.43), with a significant pattern of isolation by distance. Microsatellite loci were in genetic equilibrium, ruling out inbreeding as an important force in population structuring. Comparisons are drawn with previously published phylogeographical data. Surprisingly, introgression of nuclear genes was detected in neighbouring populations with divergent mtDNA haplotypes. These results stress the long lasting impact of colonization history and the modulating effect of gene flow at local scales in these organisms.
A cost of maternal care in the dung beetle Onthophagus taurus?
Authors: Hunt J. , Simmons L. W. , Kotiaho J. S.
Published: March 2003

Parental care theory assumes that investment in current offspring will trade against future investment. A number of field studies on birds have used clutch size manipulations to demonstrate a survival cost to chick rearing. However, such studies do not account for costs accrued during earlier stages of reproduction because not all aspects of reproductive effort are manipulated by varying the number of nestlings. In this study, we investigate the effect of reproductive effort on female survival in the dung beetle, Onthophagus taurus. By experimentally manipulating mating status and dung availability, we demonstrate that virgin females survive longer than mated females and that the survival of mated females was negatively associated with the number of brood masses produced. Using a novel manipulation of the mating system, we separated the effects of egg production and maternal care on female survival. Previously, we have shown that females provisioning with the assistance of a major male provide relatively less care than unassisted females. However, paternal assistance did not alter the number of brood masses produced and hence the amount of reproductive effort that was allocated to egg production. Therefore, our finding that female survival was increased when receiving paternal assistance provides, to our knowledge, the first definitive evidence that maternal care reduces female lifespan. These results are of major importance to theoretical models on the evolution of parental care.
Seasonal butterfly design: morphological plasticity among three developmental pathways relative to sex, flight and thermoregulation
Authors: Van Dyck H. , Wiklund C.
Published: March 2003

The temperate-zone butterfly Pararge aegeria can use three developmental pathways corresponding to different seasonal cohorts: (1) development with a pupal winter diapause resulting in early spring adults; (2) development with a larval winter diapause resulting in late-spring adults and (3) direct development resulting in summer or second generation adults. In order to test adaptive predictions, we compared variation in flight- and thermoregulation-related morphology among adult males and females from the three pathways using both field data (i.e. wild-caught butterflies) and experimental breeding data (i.e. reared under different photoperiod regimes). Morphological patterns among the pathways were largely similar in the field and rearing data. Seasonal patterns differed between the sexes for most traits, including (relative) size measures and wing colour. Our results suggest sex-related, adaptive seasonal plasticity for morphological traits related to flight behaviour in a multivoltine insect.
Effects of spatial autocorrelation, natal philopatry and phenotypic plasticity on the heritability of laying date
Authors: Van Der Jeugd H. P. , McCleery R.
Published: March 2003

We investigated the effect of spatial autocorrelation on heritability (h2) estimates of laying date and clutch size in a population of great tits Parus major. We found that h2 of laying date, but not clutch size, declined significantly with increasing distance between the nestbox of mothers and daughters. This decline was caused by a decreasing effect of spatial autocorrelation in laying date, rather than by the existence of genotype–environment interactions (GEI). After correcting for the effect of spatial autocorrelation, h2 of laying date was low (0.16 ± 0.07), but significant, and surprisingly consistent with increasing distance between parental and offspring environments. The h2 of clutch size was not much affected by spatial autocorrelation.

Most previously published estimates of the heritability of laying date include various degrees of common environment effects, which can bias estimates both upwards and downwards. We suggest that using techniques that take spatial autocorrelation into account might be a fruitful approach to estimate h2 of traits that show a high degree of plasticity.
An empirical test of the `predictability' hypothesis for the evolution of viviparity in reptiles
Authors: Shine R.
Published: March 2003

Viviparity (live-bearing) has evolved from oviparity (egg-laying) >100 times in reptile phylogeny, but the selective forces responsible remain unclear. Tinkle & Gibbons (1977) proposed that prolonged uterine retention of eggs (leading ultimately to viviparity) is favoured by natural selection when it allows the reproducing female to better predict the incubation conditions that will occur in alternative potential nest-sites, and hence select the optimal site in which to deposit her eggs. This ingenious hypothesis has never been tested empirically. Over a 7-year period, I monitored temperatures inside 124 natural nests of egg-laying scincid lizards at three different elevations in the Brindabella Range of south-eastern Australia. As a measure of thermal predictability, I used correlation coefficients from comparisons of temperatures early vs. later in incubation among nests within each site. Both the mean and standard deviation of nest temperatures were examined in this way for each week through incubation. I performed these calculations under two models: one where the female assesses nest temperatures at the time of oviposition only, and one where she monitors temperatures constantly from the usual oviposition date until the actual time of laying. These analyses falsified two major assumptions of the ‘predictability’ hypothesis. First, nest temperatures at higher elevations were no less predictable than were those at lower elevations; instead, predictability was high in all situations. Secondly, a longer delay before oviposition decreased rather than increased the predictability of thermal conditions during subsequent incubation. I conclude that critical assumptions of the ‘predictability’ hypothesis are not supported in this study system.
Population consequences of maternal effects: sex-bias in egg-laying order facilitates divergence in sexual dimorphism between bird populations
Authors: Badyaev A. V. , Hill G. E. , Whittingham L. A.
Published: March 2003

When costs and benefits of raising sons and daughters differ between environments, parents may be selected to modify their investment into male and female offspring. In two recently colonized environments, breeding female house finches (Carpodacus mexicanus) modified the sex and growth of their offspring in relation to the order in which eggs were laid in a clutch. Here we show that, in both populations, these maternal effects strongly biased frequency distribution of tarsus size of fully grown males and females and ultimately produced population divergence in this trait. Although in each population, male and female offspring show a wide range of growth patterns, maternal modifications of sex-ratio in relation to egg-laying order resulted in under-representation of the morphologies that were selected against and over-representation of morphologies that were favoured by the local selection on juveniles. The result of these maternal adjustments was fast phenotypic change in sexual size dimorphism within and between populations. Maternal manipulations of offspring morphologies may be especially important at the initial stages of population establishment in the novel environments and may have facilitated recent colonization of much of North America by the house finch.
Functional trade-offs in the limb muscles of dogs selected for running vs. fighting
Authors: Pasi B. M. , Carrier D. R.
Published: March 2003

The physical demands of rapid and economical running differ from those of physical fighting such that functional trade-offs may prevent simultaneous evolution of optimal performance in both behaviours. Here we test three hypotheses of functional trade-off by measuring determinants of limb musculoskeletal function in two breeds of domestic dogs that have undergone intense artificial selection for running (Greyhound) or fighting performance (Pit Bull). We found that Greyhounds differ from Pit Bulls in having relatively less muscle mass distally in their limbs, weaker muscles in their forelimbs than their hindlimbs, and a much greater capacity for elastic storage in the in-series tendons of the extensor muscles of their ankle joints. These observations are consistent with the hypothesis that specialization for rapid or economical running can limit fighting performance and vice versa. We suggest that functional trade-offs that prevent simultaneous evolution of optimal performance in both locomotor and fighting abilities are widespread taxonomically.
Geographic range size, life history and rates of diversification in Australian mammals
Authors: Cardillo M. , Huxtable J. S. , Bromham L.
Published: March 2003

What causes species richness to vary among different groups of organisms? Two hypotheses are that large geographical ranges and fast life history either reduce extinction rates or raise speciation rates, elevating a clade's rate of diversification. Here we present a comparative analysis of these hypotheses using data on the phylogenetic relationships, geographical ranges and life history of the terrestrial mammal fauna of Australia. By comparing species richness patterns to null models, we show that species are distributed nonrandomly among genera. Using sister-clade comparisons to control for clade age, we then find that faster diversification is significantly associated with larger geographical ranges and larger litters, but there is no evidence for an effect of body size or age at first breeding on diversification rates. We believe the most likely explanation for these patterns is that larger litters and geographical ranges increase diversification rates because they buffer species from extinction. We also discuss the possibility that positive effects of litter size and range size on diversification rates result from elevated speciation rates.
Genotyping fetal DNA by non‐invasive means: extraction from maternal plasma
Authors: Nelson M. , Eagle C. , Langshaw M. , Popp H. , Kronenberg H.
Published: March 2003

Background and Objectives

Identification of fetal DNA in maternal plasma may allow genetic analysis without the use of invasive techniques. The aim of this study was to extract DNA from maternal plasma, identify fetal material through the presence of SRY or RHD gene sequences and assess the reliability of these results.

Materials and Methods

A polymerase chain reaction (PCR) method of a commercial kit was used with primers for SRY or exon 10 of the RHD gene sequence.

Results

Multiple plasma samples were collected from 60 women who were evaluable for either SRY or RHD, or both, fetally derived DNA sequences. Fetal DNA was present in the plasma throughout the pregnancies and for some hours or days after delivery.

Conclusion

Fetal DNA can be reliably detected in maternal plasma from early in pregnancy and normally is cleared within days of delivery.
Paediatric transfusion
Authors: Simpson J. , Kinsey S.
Published: March 2003

Paediatric transfusion encompasses a wide range of clinical circumstances including the consideration of maternal antibodies, the changing nature of the transfusion recipient with respect to growth and development, and the management of inherited conditions which if optimally treated in early life may have problems which are delayed or less severe in adult life.

Whilst the transfusion of adults and children has much in common, a child cannot be considered as a scaled down adult; there are many important differences. Developmental changes are most marked in the neonate and, together with the fact that their antibodies are maternally derived, this population provide some of the most striking challenges. The increased use of intra uterine transfusion adds an extra dimension here.

A particular paediatric concern is the long‐term consequences of transfusion. It is to be hoped that paediatric transfusion recipients will live long enough that any potential problems will manifest themselves, thus the aim must be to minimize transfusion risks.
A rapid and reliable flow cytometric routine method for counting leucocytes in leucocyte‐depleted platelet concentrates
Authors: Backteman K. , Ledent E. , Berlin G. , Ernerudh J.
Published: March 2003

Background and Objectives To ensure a proper quality control it is important to use a reliable method to count low numbers of leucocytes in leucocyte‐reduced platelet concentrates (PCs).

Materials and Methods A modified flow cytometric method for counting low numbers of leucocytes, based on a reference population contained in tubes with an exact number of fluorescent beads and staining with propidium iodide was used. To increase the number of events, the original sample volume was increased.

Results There was a good correlation in the number of leucocytes (r = 0·99) between the modified flow cytometric method and microscopy of samples from unfiltered and expected numbers from serially diluted PCs. Samples from leucocyte‐reduced PCs obtained by apheresis or filtered buffy coats showed no correlation between results from the modified flow cytometric method and microscopy (Nageotte).

Conclusion Counting by microscopy gave a lower number of leucocytes than the modified flow cytometric method when counting a low number of cells. However, analysis of the serially diluted PCs proved that the modified flow cytometric method was reliable and rapid, making it suitable for clinical routine use.
Analysis of B19 virus contamination in plasma pools for manufacturing, by using a competitive polymerase chain reaction assay
Authors: Gallinella G. , Moretti E. , Nardi G. , Zuffi E. , Bonvicini F. , Bucci E. , Musiani M. , Zerbini M.
Published: March 2003

Background and Objectives The presence of B19 virus in blood poses a risk of transmission of the virus via blood or blood products. Screening processes for manufacturing should be aimed at achieving production plasma pools with B19 virus contamination levels below 104 genome equivalents/ml (geq/ml) in order to prevent transmission of infection through plasma derivatives.

Materials and Methods The suitability of a competitor plasmid as an internal analytical standard for the detection of B19 virus in plasma pools was assessed by using a competitive polymerase chain reaction (PCR) assay. Seventy‐five plasma pools, each consisting of 960 single donations, were analysed for B19 virus contamination following a lysis treatment.

Results The amount of competitor plasmid in the competitive PCR assay established, with good accuracy, a threshold value for discrimination of the viral load in plasma pools. Analysis of samples from plasma pools showed that 12% of pools were contaminated with B19 virus at levels above the set threshold value.

Conclusions The competitive PCR assay developed proved to be effective for discrimination of the B19 virus contamination level in screening of plasma pools for manufacturing.
Broad‐spectrum virus reduction in red cell concentrates using INACTINE™ PEN110 chemistry
Authors: Lazo A. , Tassello J. , Jayarama V. , Ohagen A. , Gibaja V. , Kramer E. , Marmorato A. , Billia‐Shaveet D. , Purmal A. , Brown F. , Chapman J.
Published: March 2003

Background and Objectives The risk of transmission of blood‐borne pathogens by transfusion is a persistent problem in medicine. To address this safety issue, INACTINE™ PEN110 chemistry is being utilized to develop a process for preparing pathogen‐reduced red blood cell concentrates (RBCC). The purpose of this study was to characterize the virucidal effectiveness of the INACTINE™ PEN110 chemistry in full units of RBCC by using a panel of viruses with diverse properties in composition, size and shape.

Materials and Methods The panel included four enveloped (bovine viral diarrhoea virus, pseudorabies virus, vesicular stomatitis Indiana virus and sindbis virus), six non‐enveloped (porcine parvovirus, human adenovirus 2, reovirus 3, vesicular exanthema of swine virus, bluetongue virus, and foot and mouth disease virus) and cell‐associated (human immunodeficiency) viruses. All viruses were individually spiked into CPD/AS‐1, CP2D/AS‐3 and CPD/AS‐5 RBCC units and treated with 0·1% PEN110 (vol/vol) at 22 ± 2 °C for up to 22 ± 2 h. The PEN110 treatment reaction was stopped by chemical quenching, and residual virus was assayed. The cytotoxicity effect of PEN110‐treated RBCC on indicator cells and the potential interference with the ability of the virus to infect indicator cells was determined and taken into consideration for calculating the virus‐reduction factors, to avoid underestimation or overestimation of the virus reduction.

Results The kinetics of inactivation for viruses spiked into CPD/AS‐1, CP2D/AS‐3 and CPD/AS‐5 RBCC were equivalent. All viruses analysed in this study were reduced to the limit of detection of the assay. The reduction factors for the virus panel ranged from 4·2 to 7·5 log10/ml.

Conclusions The results from the study demonstrate for the first time that a pathogen‐reduction technology for RBCC can achieve a broad‐spectrum virucidal effect against both enveloped and non‐enveloped viruses. The broad spectrum of virucidal activity of INACTINE™ PEN110, and equivalent kinetics of virus inactivation in RBCC prepared using different commercially available RBC storage solutions, demonstrate the robustness of this pathogen‐reduction process.
Neue Ansätze zur 3‐D‐Rauhigkeitsanalyse menschlicher Haut
Authors: Piche E. , Häfner H.‐M. , Hoffmann J. , Jünger M.
Published: March 2003

Zusammenfassung: Das Mikrorelief der menschlichen Haut ermöglicht aufgrund seiner Struktur den Widerstand gegenüber von außen wirkenden mechanischen Kräften. Bislang existierten indirekte Methoden zur Erfassung von Parametern des Oberflächen‐reliefes, die durch aufwendige Digitalisierungsverfahren Silikon‐Nachbildungen der Haut als Negativ‐Replikas mittels Bildanalyse, mechanischer Taster oder in neuerer Zeit auch mittels Laserprofilometrie und konfokaler Mikroskopie analysierten. Anhand der vorliegenden Untersuchungen soll ein neues direktes, aus der Metall verarbeitenden Industrie bekanntes Messverfahren  (FOITS = Fast Optical In vivo Topometry of Human Skin) zur Rauhigkeitsanalyse menschlicher Haut beschrieben werden. Es gelang bei 40 gesunden Probanden intraindividuell, in Abhängigkeit von der Lokalisation der gemessenen Hautareale, signifikante Unterschiede in nach DIN und ISO spezifizierten Rauheitskenngrößen (Ra, Rt, Rz, Rmax) darzustellen  (p < 0,05). Beim Vergleich der gesunden Hautareale mit chronischen ekzematös veränderten Arealen bei  10 Patienten mit atopischem Ekzem waren die Unterschiede in den Rauheitskenngrößen Ra, Rt, Rz, Rmax, „positives” und „negatives” Volumen offensichtlich (p < 0,001). Die Kenngrößen „positives” und „negatives” Volumen spiegelten bei Patienten mit chronischem atopischem Ekzem die Hautglättung als Therapieerfolg nach 14‐tägiger Behandlung mit Basissalben statistisch signifikant wider (p < 0,02). Mit standardisierten Methoden, wie Messung des transepidermalen Wasserverlustes (Tewameter®)  und der Hautfeuchtigkeit (Corneometer®), konnte die verbesserte Barrierefunktion der Haut nachgewiesen werden  (p < 0,05). Als Einsatzgebiete von FOITS sehen wir neben der bisherigen industriellen Anwendung im dermatologischen Bereich die Quantifizierung und Qualifizierung von Alterungsprozessen, von pathologischen Strukturveränderungen der Haut, wie sie beispielsweise in Ekzemherden oder Psoriasisplaques vorkommen, sowie der Wirkung von auf die Haut applizierten dermatologischen Externa. Die durch FOITS ermittelten mathematischen Daten sind bei einer Tiefenauflösung  < 5 µm dreidimensional visualisierbar.
Einsatz und Bedeutung von Ciclopirox‐Lack
Authors: Tietz H.‐J. , Ulbricht H.
Published: March 2003

Zusammenfassung: Onychomykosen sind weltweit verbreitet. Epidemiologische Untersuchungen beziffern den Anteil von Nagelpilzerkrankungen unter den Oberflächenmykosen mit bis zu 30 %. Onychomykosen werden von Patienten als störend und einschränkend in bezug auf Alltag und Sozialkontakte angesehen. Seit Beginn der neunziger Jahre wurden moderne Behandlungsmethoden entwickelt. Neben oralen Antimykotika spielen die antimykotischen Lacke wie Ciclopirox‐Lack, der in 45 Ländern der Erde eingesetzt wird, eine große Rolle. Der Lack ist zur Behandlung aller Formen der Onychomykose zugelassen und wirkt fungizid und sporozid. Die Wirksamkeit als Monotherapeutikum, die sich auf alle potentiellen Auslöser einer Onychomykose erstreckt, wurde in zahlreichen Studien mit unterschiedlichem Patientenklientel belegt. Durch den substanz‐spezifischen Wirkmechanismus von Ciclopirox als Nicht‐Ergosterolsynthesehemmer ergeben sich in Kombination mit oralen Antimykotika synergistische Effekte. Die Applikation auf die Nägel erfolgt mit Hilfe eines Pinsels, was den Lack für Patienten zu einem einfach anwendbaren Therapeutikum macht. Die seit der Markteinführung selten berichteten, lokal begrenzten Begleiterscheinungen lassen den Ciclopirox‐Lack als nebenwirkungsarm gelten.
Zelloberflächen‐Epitope als therapeutisches Ziel
Authors: Mrowietz U.
Published: March 2003

Zusammenfassung: Die Expression einer Vielzahl von Oberflächen‐Epitopen ist ein charakteristisches Merkmal von Immunzellen. Rezeptoren und Adhäsionsmoleküle kommen am häufigsten vor. Es ist ebenfalls charakteristisch, dass die Expression von Epitopen über eine zelluläre Aktivierung moduliert wird. Bei entzündlichen Hauterkrankungen lassen sich diese Strukturen verwenden, um nicht nur die Art der Zelle, sondern auch deren Aktivitätsstatus zu ermitteln. Die Verfügbarkeit von monoklonalen Antikörpern und Fusionsproteinen macht es auch möglich, zelluläre Oberflächen‐Epitope als Bindungsstellen zu nutzen, um therapeutische Effekte zu erzielen.  Bei der Psoriasis wurde die auf Rezeptoren ausgerichtete Therapie (receptor targeted therapy) entwickelt und in einer Vielzahl klinischer Studien erprobt. Diese Ansätze zeigten jedoch, dass nicht alle Strategien gleichermaßen effektiv sind.  In diesem Übersichtsartikel wird die Entwicklung einer auf Zelloberflächen‐Epitope ausgerichteten Therapie für Hauterkrankungen, hauptsächlich Psoriasis, beschrieben. Klinische sowie experimentelle Daten, die mit den unterschiedlichen verwendeten Substanzen ermittelt wurden, werden hinsichtlich klinischer Wirksamkeit, Sicherheit und Verträglichkeit diskutiert.
Imiquimod und die Imidazochinolone: Wirkungsmechanismus und therapeutisches Potenzial
Authors: Stanley M.A.
Published: March 2003

Zusammenfassung: Eine zentrale Entwicklung im vergangenen Jahrzehnt fand in unserem Verständnis für die Wechselwirkungen zwischen den angeborenen und erworbenen Immunreaktionen und deren Abhängigkeit voneinander statt. Die angeborene Immunität erkennt „gefährliche” Signale und aktiviert das erworbene Immunsystem in einer gezielten, angemessenen und effektiven Reaktion. Dendritischen Zellen und Makrophagen kommen in diesem Prozess eine zentrale Bedeutung zu und pharmakologische Substanzen, die die Funktionen dieser Zellen modulieren, könnten einen therapeutischen Wert haben. Derartige Moleküle sind die Imidazochinolon‐Verbindungen, von denen Imiquimod in Form des Präparats Aldara® das bislang am besten bekannte ist. Imiquimod und seine Homologe wirken durch die Aktivierung von Makrophagen und anderen Zellen über Bindung an Zelloberflächen‐Rezeptoren wie Toll‐Rezeptor 7, wodurch sie die Sekretion proinflammatorischer Zytokine induzieren, vorwiegend Interferon (IFN)‐α, Tumornekrosefaktor (TNF)‐α und Interleukin (IL)‐12. Dieses lokal gebildete Zytokin‐Milieu zielt auf eine über Th1‐Zellen vermittelte Immunreaktion mit Bildung zytotoxischer Effektoren ab. Dies wurde klinisch in der Therapie viraler Infektionen (humanes Papillomavirus, Herpes simplex Virus, Molluscum contagiosum) und von nicht melanomatösem Hautkrebs untersucht. Imiquimod hat sich zur Elimination genitaler Warzen als signifikant wirksamer als Placebo erwiesen; Studien zum Wirkungsmechanismus weisen darauf hin, dass dies im Zusammenhang mit dem Vermögen der Bildung proinflammatorischer Zytokine und einer Th1‐Rekation steht. Intraepitheliale Neoplasmen kutaner und muköser Oberflächen stehen im Zusammenhang mit Infektionen mit dem humanen Papillomavirus und es gibt einige Hinweise darauf, dass Modifikatoren der Immunreaktion bei derartigen pathologischen Veränderungen einen therapeutischen Wert haben könnten. Eine lokale Immuntherapie mit Immunmodulatoren zeigt ein Potential für eine effektive und patientenfreundliche Therapie kutaner Virusinfektionen. Diese Substanzen haben auch weitere Eigenschaften, durch die konventionelle Impfstrategien signifikant verbessert werden könnten.
Melanomvakzinierung
Authors: Nestle F.O.
Published: March 2003

Zusammenfassung: Das Melanom ist ein typischer immunogener Tumor. Unterschiedliche Formen der Immuntherapie wurden in den letzten Jahrzehnten für diesen Tumor entwickelt, allerdings ohne durchschlagenden Erfolg. In den letzen Jahren erzielte wissenschaftliche Fortschritte liegen im Bereich der Charakterisierung von Tumorantigenen, neuen Methoden zur Detektion einer Anti‐Tumor spezifischen Immunantwort und der Verwendung von natürlichen Adjuvantien wie z. B. dendritischen Zellen.