bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine needle aspiration cytology in the work‐up of mammographic and ultrasonographic findings in breast cancer screening: an attempt at differentiating in situ and invasive carcinoma
Authors: SAUER TORILL , YOUNG KARI , THORESEN STEINAR ØSTERBØ
Published: March 2003

Fine needle aspiration cytology in the work‐up of mammographic and ultrasonographic findings in breast cancer screening: an attempt at differentiating

in situ

and invasive carcinoma

This study evaluated the results of fine needle aspiration cytology (FNAC) from the first four years of organized mammography screening for breast cancer in Oslo, particularly our policy in differentiating in situ and invasive carcinoma. Lesions were aspirated directly, ultrasound guided, by stereotaxic device or biopsy localization plate. All lesions were aspirated by cytopathologists working with the radiologists at the breast diagnostic centre. Smears were evaluated immediately for assessment of adequacy and a preliminary diagnosis was given to the surgeon. When FNAC revealed malignancy, diagnostic terms were as follows: (1) invasive carcinoma; (2) ductal carcinoma in situ of comedo type (high nuclear grade), cannot evaluate infiltration; (3) ductal carcinoma in situ of low nuclear grade and (4) papillary tumour, cannot evaluate infiltration. There were 953 cases, 70% of which were nonpalpable. Insufficient material was obtained in 5.8%. Absolute and complete sensitivity were 81% and 91%, respectively. Specificity was 85%. There were 448 histologically proven carcinomas. 383 of these were invasive. 362 carcinomas (in situ and invasive) (80.8%) were diagnosed directly on FNAC. Distinction between invasive and in situ carcinoma was possible in 294 of 320 directly diagnosed invasive carcinomas (91.8%). PPV of a diagnosis of invasive carcinoma was 97%. Our data showed that definitive cytological diagnosis of invasive carcinoma was possible in more than 90% of fully diagnostic smears and allowed definitive primary surgery in these women.
Cytology of collagenous spherulosis of the breast: a diagnostic dilemma – report of three cases
Authors: JAIN SHYAMA , KUMAR NEETA , SODHANI PUSHPA , GUPTA SANJAY
Published: March 2003

Cytology of collagenous spherulosis of the breast: a diagnostic dilemma‐report of three cases

Collagenous spherulosis is a rare incidental finding seen in association with benign breast lesions. Cytological findings in three cases of collagenous spherulosis diagnosed on fine needle aspiration are presented. The presence of hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained smears was a diagnostic feature. Associated lesions were atypical papillary hyperplasia (2) and fibroadenoma (1). Adenoid cystic carcinoma was the close differential diagnosis on cytology. Awareness of this entity is important to avoid a false positive diagnosis of malignancy.
Cytological features of chronic follicular cervicitis in liquid‐based specimens: a potential diagnostic pitfall
Authors: Halford J. A.
Published: March 2003

A review of negative split‐sample cervical cytology cases revealed five cases reported as chronic follicular cervicitis. These cases showed characteristic morphological features in conventional smears with lymphoid cells, plasma cells and tingible body macrophages smeared across the slides. This contrasts with the presentation of ThinPrep® samples (Cytic Corporation, Boxburgh, MA, USA), where cells were observed aggregated in clumps. The different presentation noted in liquid‐based samples may require careful microscopic evaluation at high‐power magnification.
Determination of adult size in a folivorous moth: constraints at instar level?
Authors: TAMMARU TOOMAS
Published: March 2003

1. Reaction norms for size and age at maturity were studied in Epirrita autumnata (Lepidoptera, Geometridae). Growth rates were manipulated by rearing larvae on different levels of food quality and quantity, and instar‐specific final weights and development times were recorded.

2. Food level and initial weight of an instar accounted for most of the variance in final weights. Sexual dimorphism in pupal weights could be entirely ascribed to sex differences in initial weights of the last instar.

3. There were problems with considering the reaction norms optimal within the conventional demographic explanatory framework. Because fecundity increases linearly with body size and no costs of large adult size are known, one should expect female larvae to grow larger to increase their individual fitness. It is therefore likely that constraints play a major role in the determination, and evolution, of size in this species.

4. A focus on individual instars may be the best way to reveal the constraints on, and space for, adaptive evolution of insect growth. Some limit to the initial:final weight ratio of an instar, and the fixed number of instars, may represent important constraints.

5. Reaction norms like the ones described in this study lead to strong environmental determination rather than canalization of body size. Food quality throughout larval development may thus be very important for individual fitness and population dynamics in E. autumnata.
Differences in distribution and performance of two sap‐sucking herbivores on glandular and non‐glandular Datura wrightii
Authors: Van DAM NICOLE M. , HARE DANIEL J.
Published: March 2003

1. Datura wrightii Regel (Solanaceae) is polymorphic with regard to trichome type. Some plants are densely covered with short, non‐glandular trichomes, whereas other plants in the same populations possess glandular trichomes that excrete a sticky exudate. The hypothesis that glandular trichomes enhance resistance to all small insect herbivores is evaluated.

2. Field censuses in four southern Californian D. wrightii plant populations revealed that glandular plants are indeed resistant to whitefly spp. (Homoptera: Aleyrodidae). Whiteflies are almost exclusively found on non‐glandular plants. In contrast, Tupiocoris notatus (Distant) (Heteroptera: Miridae), another sap‐sucking herbivore of similar body size, is found predominantly on plants with glandular trichomes.

3. Laboratory experiments showed that whiteflies are unable to colonize glandular D. wrightii phenotypes. After the whitefly adults had landed on the leaves of these plants, they were trapped in the exudate and died.

4. Tupiocoris notatus adults, on the other hand, laid significantly more eggs on glandular plants. The presence of the exudate was shown to be the cue that determined their choice of glandular plants.

5. In no‐choice experiments, T. notatus nymphs reared on glandular plants had significantly higher survival rates and had shorter developmental periods than those raised on non‐glandular plants. This, combined with the higher oviposition rates, resulted in higher T. notatus population growth rates on glandular plants than on non‐glandular plants.

6. Glandular trichomes are not therefore a universal protection against small herbivores. Differences in distribution over the two plant types within the natural herbivore guild on D. wrightii may, among other selection pressures, contribute to the maintenance of the observed trichome polymorphism.
The utilization of patchy thermal microhabitats by the ectothermic insect predator, Cicindela sexguttata
Authors: Schultz Tom. D.
Published: March 2003

Abstract.1. Tiger beetles (Cicindela) of open habitats have served as model ectotherms in studies of the dependence of activity and habitat utilization on temperature. Potential departures from the cicindelid model were investigated in Cicindela sexguttata, a species inhabiting forests where thermal resources are patchy and ephemeral.

2. Body temperatures (Tb) were determined by inserting thermocouples into beetles immediately after observing specific behaviours in the field. Cicindela sexguttata elevated Tb by basking, foraged at a preferred Tb of 32.8 °C, and stilted, sun‐faced, or sought shade when Tb exceeded 35 °C. Although these behaviours were typical of Cicindela, their set points were lower than those of species in more open habitats.

3. Illuminated substrates were utilized for basking and foraging. Beetles were dispersed throughout the forest floor in early spring, but became aggregated in light gaps when the canopy leafed out. Operative temperatures of thermal models indicated that beetles were unable to maintain the preferred Tb in shade and would not be able to maintain a preferred Tb in light gaps during the autumn, when adults are normally in diapause.

4. Beetles were confined to foraging in light gaps once the canopy was closed. Foraging rate and searching speed were independent of Tb, in contrast to other cicindelids. Adults rarely searched for prey, but ambushed small arthropods that alighted in the light gap. Dependence on patches of illumination as thermal resources may increase prey capture, intraspecific encounters, and risk of predation, and preclude foraging in the autumn when Cicindela species of open habitats are also active.
Late autumn eclosion in the winter moth Operophtera brumata: compromise of selective forces in life‐cycle timing
Authors: Peterson Nancy A. , Nilssen Arne. C.
Published: March 2003

Abstract.1. In eclosion experiments at constant temperatures (6, 9, 12, 15, 18, 21, and 25 °C), Operophtera brumata (L.) pupae were found to respond nonlinearly to temperature, with 9 °C giving the highest developmental rate.

2. Pupal development rate decreased and mortality increased at the highest and lowest temperatures. No pupae eclosed at 6, 21, or 25 °C.

3. Exposing pupae to periods of cold did not enhance their rate of development consistently, indicating that no pupal diapause occurred. Light did not affect the length of the pupal period significantly.

4. Variation in mean developmental rates across temperatures was modelled both for data in the present study (northern Norway) and for a previously published German study (20° further south). The German population had a longer pupal period at all temperatures than the northern population (mean difference of 88 days). The difference is assumed to be genetically based, and hence an adaption to (and not a consequence of) differences in phenology between the two sites.

5. The diversity of the life cycle of O. brumata is discussed. Timing of eclosion can be explained by the selective forces of predation by birds on the one hand and mortality due to early snowfall on the other.
Compound effects of induced plant responses on insect herbivores and parasitoids: implications for tritrophic interactions
Authors: Havill Nathan P. , Raffa Kenneth F.
Published: March 2003

1. Induced plant responses can affect herbivores either directly, by reducing herbivore development, or indirectly, by affecting the performance of natural enemies. Both the direct and indirect impacts of induction on herbivore and parasitoid success were evaluated in a common experimental system, using clonal poplar treesPopulus nigra(Salicales: Salicaceae), the gypsy mothLymantria dispar(L.) (Lepidoptera: Lymantriidae), and the gregarious parasitoidGlyptapanteles flavicoxis(Marsh) (Hymenoptera: Braconidae).

2. Female parasitoids were attracted to leaf odours from both damaged and undamaged trees, however herbivore‐damaged leaves were three times more attractive to wasps than undamaged leaves. Parasitoids were also attracted to herbivore larvae reared on foliage and to larval frass, but they were not attracted to larvae reared on artificial diet.

3. Prior gypsy moth feeding elicited a systemic plant response that retarded the growth rate, feeding, and survival of gypsy moth larvae, however induction also reduced the developmental success of the parasitoid.

4. The mean number of parasitoid progeny emerging from hosts fed foliage from induced trees was 40% less than from uninduced trees. In addition, the proportion of parasitised larvae that survived long enough to issue any parasitoids was lower on foliage from induced trees.

5. A conceptual and analytical model is provided to describe the net impacts of induced plant responses on parasitoids, and implications for tritrophic interactions and biological control of insect pests are discussed.
Structure of two macrolepidopteran assemblages on Salix nigra (Marsh) and Acer negundo L.: abundance, diversity, richness, and persistence of scarce species
Authors: Barbosa Pedro , Segarra Alejandro , Gross Paul
Published: March 2003

1. Most insect species occur at low abundance but a greater research effort has been devoted to so‐called outbreak species and little research is available on scarce (low abundance) species that are typical of most insect species.

2. Larval free‐feeding macrolepidoptera of two riparian trees Salix nigra (Marsh) (black willow) and Acer negundo L. (box elder) were sampled and sorted by species and abundance.

3. Data collected established that the majority of species in the assemblages in each tree species occurred at low abundance in each of the 5 years when larvae were sampled.

4. Species in the Noctuidae and Geometridae dominated both assemblages.

5. On both trees, assemblages were dominated numerically by relatively few species, a pattern that has been observed for insect assemblages on plants in managed and unmanaged habitats.
Vigour of a dioecious shrub and attack by a galling herbivore
Authors: Faria Maurício L. , Fernandes G. Wilson
Published: March 2003

1. The pattern of attack by the leaf‐galling insect Neopelma baccharidis (Homoptera: Psyllidae) was studied in three populations of the dioecious shrub Baccharis dracunculifolia (Asteraceae) in south‐eastern Brazil. The plant vigour hypothesis, which predicts higher rates of attack and increased herbivore performance on the longest plant shoots, was tested. This work also provides further information for the study of differential herbivory in dioecious plants.

2. In total, 9200 shoots were collected randomly from 46 male and 47 female plants belonging to the three populations. Shoot length, number of leaves per shoot, rate of galling, and survival of psyllids did not differ between male and female plants. Another population on the Campus of the Federal University of Minas Gerais was used only to determine the pattern of shoot growth.

3. The hypothesis of sex‐mediated herbivory was not corroborated in this study.

4. The frequency of galling increased with increasing shoot length, as predicted by the plant vigour hypothesis. Nevertheless, the number of oviposition sites (leaf buds) increased with shoot length.

5. The performance of the galling herbivore was not related to shoot length in the plant populations studied.

6. In conclusion, Neopelma baccharidis did not select shoots based on length only.
The pattern, rate, and range of within‐patch movement of a stem‐galling fly
Authors: Cronin J. T. , Hyland K. , Abrahamson W. G.
Published: March 2003

1. Information on the movement of insects is critical to understanding the spatial spread, dynamics, and genetic structure of their populations, as well as their interactions with other species. With this in mind, the movement behaviour of the stem‐galling fly Eurosta solidaginis Fitch (Diptera: Tephritidae) was investigated.

2. Fluorescent‐marked adults were released at a single location within pure patches of the host plant, tall goldenrod Solidago altissima, and their distributions censused repeatedly throughout the day.

3. Following their release, male and female flies redistributed themselves in a manner that was well described by a simple‐diffusion model. The diffusion rate was independent of fly density and time since flies were released.

4. Female flies dispersed at a significantly faster rate, and therefore farther on average, than males. Based on the diffusion model, it was estimated that at 2.5–3.0 h post release, males and females had a median dispersal distance of only 2.0 and 2.5 m respectively. Furthermore, 95% of the males were estimated to have dispersed no more than 5.9 m, and females no more than 6.4 m.

5. Post‐release censuses suggested that flies were most active during mid morning, disappeared from the site at a rate of 10–15% per hour (most likely due to mortality), and survived for less than 2 days. Based on the rate of spread, diel activity, and liberal estimates of longevity in the field, 50% of the ovipositing females were predicted to have had a maximum lifetime range of movement within a patch of hosts of ≤ 51 m (95% were expected to have been limited to ≤ 130 m).

6. These data are used to assess whether the absence of a positive correlation between host‐plant preference and offspring performance in this system could be due to the limited scale of dispersal of this species relative to the spatial scale at which its oviposition behaviour has been studied.
Variable maternal control of facultative egg diapause in the bushcricket Ephippiger ephippiger
Authors: Hockham Leon R. , Graves Jeff A. , Ritchie Michael G.
Published: March 2003

1. Diapause is a term used to describe an arrest in the development of insects as adults, eggs, or embryos, and allows survival during adverse environmental conditions.

2. The influence of maternal age on the proportion of eggs that entered an initial facultative diapause and on fecundity and egg mortality was investigated in the bushcricket Ephippiger ephippiger.

3. In the absence of variable abiotic cues such as temperature and photoperiod, most E. ephippiger females increase the proportion of their eggs that enter diapause as they age, however there are large differences among females, with a minority showing different trends. Fecundity and egg survival decline with female age and also differ among females.

4. The influence of age on the incidence of diapause is likely to be an adaptive reproductive strategy, as those eggs laid later in the season are unlikely to complete egg development before the onset of winter. Females are probably hedging their bets by diversifying the rate of development among their offspring and effectively spreading development over several seasons. The low predictability of future environmental conditions might explain the heterogeneity of female reproductive strategies.
Nutritional benefits of the leaf‐mining behaviour of two grass miners: a test of the selective feeding hypothesis
Authors: Scheirs J. , De Bruyn L. , Verhagen R.
Published: March 2003

1. The selective feeding hypothesis predicts that miners prefer tissues high in nutrient content and low in chemical and structural defence content. This hypothesis was tested for two dipteran grass miners, Chromatomyia milii and C. nigra, feeding on Holcus lanatus.

2. Leaf sections revealed that both miners preferred to feed on the mesophyll layer, minimised the intake of veinal tissues, and never fed on the epidermal layer. Nutritional quality analyses showed that the mesophyll had a higher nutrient content and a lower structural defence content than the epidermal and veinal tissues.

3. The nutritional quality of mined leaf areas was lower than that of unmined leaf areas, suggesting that the mining larvae remove the most nutritious tissues; however this commonly used approach for studying the selective feeding hypothesis is questioned in this study.

4. Larval feeding rates were higher on the mesophyll than on the veinal tissues, probably due to a higher structural defence content of the veins. Feeding rates were higher on the small veins than on the larger and more sclerified, strengthened veins.

5. This study supports the selective feeding hypothesis as both species concentrated their feeding on the mesophyll, which is the most nutritious and least tough tissue within a H. lanatus leaf.
Dispersal by bagworm larvae, Metisa plana: effects of population density, larval sex, and host plant attributes
Authors: Rhainds Marc , Gries Gerhard , Ho Cheng Tuck , Chew Poh Soon
Published: March 2003

Abstract 1. The work reported here investigated the incidence of dispersal by bagworm larvae Metisa plana (Walker) (Lepidoptera: Psychidae), a species with apterous females and winged males.

2. A mark–recapture study conducted in a plantation of oil palm revealed that a significant proportion of larvae undertakes multiple episodes of ballooning, and suggested that ballooning represents a strategy for foraging both within and between hosts.

3. Experiments conducted in a controlled cage environment indicated that increasing population density and defoliation of oil palm both promote dispersal by larvae.

4. Neonatal larvae typically remained on the host where they emerged, indicating that pupation site of late‐instar females influences the distribution of their progeny, and suggesting a high level of genetic relatedness in localised bagworm populations.

5. Density‐dependent dispersal may generate relatively uniform distributions of M. plana in plantations of oil palm, by simultaneously stabilising populations on heavily infested palms and redistributing larvae on lightly infested palms.

6. The rate of ballooning was greater for female than for male larvae, possibly resulting from the sex‐specific impact of population density on reproductive success or from late‐instar females seeking suitable oviposition sites for their future progeny.
Differences in host plant selection among three Athalia sawflies feeding on crucifers in Japan
Authors: Nagasaka Koukichi , Ohsaki Naota
Published: March 2003

Abstract 1. The ways of using host plants were compared among the three Athalia sawflies [A. japonica (Klug), A. rosae ruficornis Jakovlev, and A. infumata (Marlatt)] feeding on crucifers in Japan to determine whether host specialisation can explain the difference in their life‐history traits. The occurrence of their larvae was examined on each crucifer species in the field, and the suitability of each crucifer species for the three successive steps of host use by the sawflies was evaluated: microhabitat selection by adult females, female oviposition, and larval growth.

2. There were 11 species of crucifer in the study area, and A. japonica, A. rosae, and A. infumata used nine, seven, and eight species respectively. Thus, sawfly host ranges overlapped.

3. Adult females of A. japonica, A. rosae, and A. infumata preferred shady clumps of crucifers, sunny clumps of crucifers, and disturbed areas respectively.

4. Unsuitable hosts for larval performance such as Brassica oleracea and Arabis plants were eliminated from the host ranges of the three sawflies.

5. Once they chose microhabitats, the suitability of each host plant for female oviposition and larval growth was similar.

6. Because of the divergent preferences for microhabitats, the host plants that were suitable for all the three steps were restricted to different sets of plants among the sawflies: Cardamine for A. japonica, cultivated crucifers (Raphanus and Brassica) for A. rosae, and Rorippa for A. infumata. These plants could be recognised as the respective primary host plants.

7. The spatio‐temporal distributions of primary hosts were consistent with and explained the pattern of diapause and migration of each sawfly, suggesting that host specialisation caused their life‐history traits to differentiate.
Community effects of praying mantids: a meta‐analysis of the influences of species identity and experimental design
Authors: Fagan William F. , Moran Matthew D. , Rango Jessamy J. , Hurd Lawrence E.
Published: March 2003

Abstract  1. Generalist arthropod predators are ubiquitous in terrestrial ecosystems but experimental studies have yielded little agreement as to their effects on prey assemblages. Drawing on results from a suite of experimental field studies, a meta‐analysis was conducted of the impact of praying mantids (Mantodea: Mantidae) on arthropod assemblages in order to identify predictable and unpredictable effects of these extremely generalised predators.

2. Results across different experiments were synthesised using the log response ratio framework, with a focus on quantifying net mantid impacts on arthropod density across taxonomic orders and trophic levels of arthropods, paying special attention to the contribution of mantid species identity and experimental design variables, such as the use of cages, length of experiment, and manipulated mantid density.

3. Calculated on a per mantid‐day basis, the net impacts of Tenodera sinensis on arthropod density were generally weaker but more predictable than the effects of Mantis religiosa. Mantids in general had weak negative effects on density for most taxa but exhibited strong negative and positive effects on some taxa. Tenodera sinensis tended to have negative effects on Homoptera, Diptera, and Hemiptera and herbivores as a group, however M. religiosa exhibited greater variation in response of different taxa that appeared to be affected more strongly by experimental design. The effects of Stagmomantis carolina tended to be negative or non‐significant.

4. Experimental cages had little influence on either the sign or magnitude of net community impacts for T. sinensis, however cage experiments reversed the sign of the mean effect for two of six taxonomic orders when the experimental predator was M. religiosa. Cages also increased the variability of effect size greatly for M. religiosa but not for T. sinensis.

5. It was concluded that it is possible to use log response ratios to determine general, predictable trends in a well‐studied system. Similar meta‐analyses of generalist predator effects in other systems should produce predictions of how these predators influence food webs, an important step towards defining more clearly the influences of generalist predators on community structure and dynamics.
The effects of exposure to seaweed on willingness to mate, oviposition, and longevity in seaweed flies
Authors: Dunn Derek W. , Crean Caroline S. , Gilburn André s.
Published: March 2003

Abstract  1. Large male seaweed flies (Diptera: Coelopidae) are more likely to mate than smaller males. This is due to sexual conflict over mating, by which females physically resist male attempts to copulate. In some species, large males are simply more efficient at overpowering female resistance.

2. Female reluctance to mate is likely to have evolved due to the costs of mating to females. In many dipterans, males manipulate female behaviour through seminal proteins that have evolved through sperm competition. This behavioural manipulation can be costly to females, for example forcing females to oviposit in sub‐optimal conditions and increasing their mortality.

3. Previous work has failed to identify any ubiquitous costs of mating to female coelopids. The work reported here was designed to investigate the effects of exposure to oviposition sites (Fucus algae) on the reproductive behaviour of four species of coelopid. Algae deposition in nature is stochastic and females mate with multiple males in and around oviposition sites. Spermatogenesis is restricted to the pupal stage and there is last‐male sperm precedence. It was predicted that males would avoid wasting sperm and would be more willing to mate, and to remain paired with females for longer, when exposed to oviposition material compared with control males. Females were predicted to incur longevity costs of mating if mating increased their rate of oviposition, especially in the presence of algae.

4. The behaviour of males of all four species concurred with the predictions; however mating did not affect female receptivity, oviposition behaviour, or longevity. Exposure to algae induced oviposition and increased female mortality in all species independently of mating and egg production. The evolutionary ecology of potential costs of mating to female coelopids are discussed in the light of these findings.
Premiers résultats de lutte biologique par les souches K84 et K1026 contre Agrobacterium radiobacter var. tumefaciens, agent du crown‐gall des rosacées fruitières et du rosier au Maroc
Authors: Benjama A. , Redwane A. , El Gadda M. , El Medraoui L. , Ouzrit M. , Boussad L. , El Ouard R. , Nesme X.
Published: March 2003

Une collection de 206 souches marocaines d’Agrobacterium radiobacter var. tumefaciens a été testée vis‐à‐vis des souches antagonistes Agrobacterium radiobacter K84 et K1026in vitro. Ce test d’antagonisme a montré que la sensibilité des souches varie en fonction de la souche antagoniste, du biovar et de la plante‐hôte d’origine. La K1026 s’est avérée meilleure que la K84 aussi bien par le nombre et par le diamètre plus élevé. Des essais au champ ont montré une bonne efficacité de la souche antagoniste K84 en seaux ou en sol naturellement infesté. La réussite de la lutte biologique avec la K84 varie entre 70% et 95% sur GF677, rosier, amandier amer et pêcher par rapport aux témoins sans K84, alors que l’abricotier s’est montré résistant au crown‐gall aussi bien en sol inoculé qu’en sol naturellement infesté. Nous pensons généraliser cette lutte dans tous les foyers marocains à crown‐gall avec une souche mutante de la K84, la K1026, qui a donné aussi une satisfaction meilleure in vitro dans d’autres pays méditerranéens comme l’Espagne, la France et l’Italie.
Direct gene transfer into the rat pancreas using DNA‐liposomes
Authors: Schmid  , Weidenbach  , Yamagushi  , Lührs  , Liptay  , Adler
Published: March 2003

Background

Pancreatic cancer represents a malignancy with very poor clinical prognosis and limited therapeutic potential. Recent developments of gene transfer technology offer new therapeutic avenues by delivering recombinant genes directly into normal or neoplastic tissue in vivo.

Methods

Here we show that the LacZ marker gene, complexed to cationic liposomes, can be introduced into the pancreas by either intraductal or intra‐arterial injection. Expression of the β‐galactosidase gene product was monitored by polymerase chain reaction and histochemistry.

Results

Up to 28 days after in vivo gene transfer, β‐galactosidase activity could be demonstrated in the pancreas. Intraductal application induced gene expression in lining duct cells preferentially. Twenty‐four hours after intraductal injection of liposomes, a dose‐dependent, transient increase in serum amylase levels was detected. Nevertheless, no histological signs of pancreatitis were evident. Intra‐arterial injection resulted in β‐galactosidase expression in endothelial cells of intrapancreatic arteries, as well as in the spleen, lymph nodes and liver, but not in ductal cells of the pancreas. Only occasionally were acinar cells positive for blue staining by either type of treatment.

Conclusion

These experiments demonstrate that in vivo gene transfer into the pancreas is feasible using DNA–liposome complexes. Furthermore, the route of administration largely determines cell type specificity and side‐effects. This technique might have an impact for the development of gene therapy strategies for pancreatic diseases.
Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial cell line
Authors: Pottratz  , Reese  , Sheldon
Published: March 2003

Background

Pneumocystis carinii (PC) infection often results in severe pneumonia in immunocompromised patients. Attachment of PC organisms to alveolar epithelial cells is a hallmark of PC pneumonia; however, few studies have investigated the response of alveolar epithelial cells to PC infection.

Methods

Interleukin 6 (IL‐6) is a multifunctional cytokine that is produced by alveolar epithelial cells in response to a variety of stimuli. Our investigation was undertaken to determine whether PC organisms induce production of IL‐6 by alveolar epithelial cells and to determine the effect of IL‐6 on PC attachment.

Results

Incubation of the human alveolar epithelial cell line, A549, with PC organisms resulted in a significant increase in IL‐6 secreted into the cell culture media. Time‐course studies showed that IL‐6 production was detected as soon as 2 h after addition of PC and continued up to 48 h of exposure. Further studies demonstrated that preincubation of A549 cells with IL‐6 resulted in a concentration‐dependent increase in both A549 cell production of fibronectin and PC attachment.

Conclusion

Thus, PC attachment to an alveolar epithelial cell line results in epithelial cell production of IL‐6, which can act to further increase PC attachment. This may provide an important mechanism whereby PC organisms directly affect the host response to PC infection.
Use of cholesterol precursors to assess changes in cholesterol synthesis under non‐steady‐state conditions
Authors: Pfohl  , Naoumova  , Kim  , Thompson
Published: March 2003

Background

Quantification of plasma levels of an early and late intermediate on the cholesterol pathway, mevalonic acid (MVA) and lathosterol respectively, provides a useful method of estimating cholesterol synthesis in humans. The aim of this study was to assess further their roles as indices of cholesterol synthesis under non‐steady‐state conditions.

Methods

The short‐term effects of pharmacological inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase on both variables were determined in four normolipidaemic subjects during and after treatment with simvastatin 20 mg daily. Plasma MVA was measured using gas chromatography–mass spectrometry, and lathosterol using gas chromatography.

Results

A single dose of 20 mg of simvastatin decreased plasma MVA after 2 h and decreased the lathosterol–cholesterol (L/C) ratio after 4 h. Treatment with simvastatin 20 mg daily for 9 days decreased both variables by approximately 50%, the nadir of plasma MVA occurring on the second day and of the L/C ratio on the fifth day, and resulted in a 39% reduction in low‐density lipoprotein (LDL)‐cholesterol. After discontinuing simvastatin, there were rebounds in plasma MVA and the L/C ratio to above basal levels but not in LDL cholesterol or apolipoprotein B (apoB), the latter continuing to decrease for a further 2 days.

Conclusion

These results suggest that simvastatin rapidly down‐regulates cholesterol synthesis, which is then up‐regulated when the drug is withdrawn.
The association of type II pneumocytes and endothelial permeability with the pulmonary custocyte system in experimental acute pancreatitis
Authors: Wang  , Börjesson  , Sun  , Wallèn  , Deng  , Zhang  , Hallberg  , Andersson
Published: March 2003

Background

Pancreatitis‐associated pulmonary injury is still associated with substantial mortality, especially when seen as a part of the multiple organ dysfunction syndrome.

Methods

The present study aimed at evaluating alterations in type II pneumocytes and the potential relationship with the development of pulmonary injury after acute haemorrhagic pancreatitis induced by an intraductal infusion of 5% sodium taurodeoxycholate in the rat.

Results

The results demonstrated that definite alterations in type II pneumocytes were noted 12 and 24 h after induction of pancreatitis, characterized by an increase in the number of vocalized lamellae, the exposed area of type II pneumocytes to alveolar airspace, cellular separation and apoptosis without alterations in cellular membrane integrity. Dysfunction of the pulmonary endothelial barrier was evidenced by an increase in pulmonary albumin flux and the leakage index as well as the migration of lanthanum probes from capillaries to interstitial tissues. The levels of tumour necrosis factor (TNF) in bronchoalveolar lavage fluid significantly increased during the initial phase (3 and 6 h) after pancreatitis. The phagocytic activity of the pulmonary custocyte system increased 3 and 12 h after induction of pancreatitis.

Conclusion

Thus, pulmonary endothelial barrier dysfunction, an activated custocyte system, and initial release of TNF seems to be involved in the pathogenesis of pancreatitis‐associated type II pneumocyte compromise.
Association of high plasma antioxidant capacity with new lesion formation in carotid atherosclerosis: a prospective study
Authors: Reinisch  , Kiechl  , Mayr  , Schratzberger  , Dunzendorfer  , Kähler  , Buratti  , Willeit  , Wiedermann
Published: March 2003

Background

In atherosclerosis, both reductions and elevations in plasma levels of antioxidants have been reported. This study investigated total antioxidant capacity of plasma from subjects with atherosclerotic disease.

Materials and methods

The study population consisted of 48 men with or without carotid atherosclerosis. At baseline (1990) carotid arteries were evaluated by duplex sonography and plasma samples were obtained for testing antioxidant capacity by two different test systems. One assay system used neutrophils from healthy volunteers as a source of oxygen free radicals activating the non‐fluorescent dichlorofluorescin diacetate in the presence of antioxidant containing plasma from study subjects. In the other test system, total plasma antioxidants were detected colorimetrically by using 2,2′‐azino‐di‐(3‐ethylbenzthiazoline sulphonate), metmyoglobin and superoxide in the presence of plasma. Carotid arteries were re‐evaluated for the development of new plaques 5 years later (1995).

Results

Increased baseline total antioxidant capacity of plasma was significantly associated with the development of new atherosclerotic lesions during a period of 5 years.

Conclusions

Endogenous antioxidant capacity of plasma is increased in patients with active atherosclerotic disease. As scavenging of oxygen free radicals is thought to protect from atherogenesis, elevated antioxidative capacity may represent an adaptive mechanism.
Impaired glycolysis and protein catabolism induced by acid in L6 rat muscle cells
Authors: Bevington  , Brown  , Pratt  , Messer  , Walls
Published: March 2003

Background

In skeletal muscle, metabolic acidosis stimulates protein degradation and oxidation of branched‐chain amino acids. This could occur to compensate for impairment of glucose utilization induced by acid.

Methods

To test this hypothesis, glycolysis and protein degradation (release of [14C]‐phenylalanine) were measured in L6 skeletal muscle cells cultured in Eagle's minimum essential medium at pH 7.1 or 7.5 for up to 3 days.

Results

No marked changes in total DNA or in cell viability were detected, nor was there any significant effect on intracellular pH or the water content of the cells (which is thought to be a key regulator of protein turnover, especially in liver). In spite of this, acid stimulated protein degradation, induced net protein loss from the cultures, inhibited glucose uptake and glycolysis (lactate output) and was associated with increased [1‐14C]‐leucine oxidation. Effects on protein degradation and glycolysis were gradual, reaching a maximum after 20–30 h. To investigate whether glycolytic flux itself can influence protein degradation, increased glycolysis was simulated by adding glucose (20 mmol L−1) or pyruvate (1 mmol L−1) to the medium. At pH 7.1, neither addition had any effect on protein degradation.

Conclusion

Although acid‐induced protein wasting is associated with impaired glycolysis, no obligatory coupling exists between glycolytic flux and protein degradation.
Gestational hypertension plasma and human umbilical vein endothelial cells: an in vitro study
Authors: Cester  , Salvolini  , Rabini  , Tranquilli  , Zolese  , Mazzanti
Published: March 2003

Background

The action of plasma from women affected by gestational hypertension (GH) on nitric oxide synthase (NOS) activity in cultured human umbilical vein endothelial cells (HUVECs) was evaluated in the present study, together with the effect on cytosolic calcium, on Na+, K+‐ATPase activity and on membrane fluidity.

Methods

At 80% confluence, cultured HUVECs were incubated for 3 h at 37°C with fresh culture medium (control samples) or with 20% (v/v) plasma (from five healthy non‐pregnant women, five healthy pregnant women and five pregnant women affected by GH).

Results

After incubation with GH plasma, we observed a significant reduction in NOS activity, intracellular calcium concentrations and Na+, K+‐ATPase activity.

Conclusions

The present work gives further support to the hypothesis that a circulating factor in gestational hypertension, possibly produced by the fetoplacental unit, causes dysfunction of the vascular endothelial cells and NO reduction, resulting in a loss of vascular refractoriness to vasoactive agents.
Pharmacological intervention: the antiobesity approach
Authors: Rissanen
Published: March 2003

Reduction in overweight and obesity management have been shown to be important in the treatment of diabetes. Even modest weight loss produces important metabolic benefits if maintained over the long term. Thus a pharmacotherapeutic agent that could produce a maintained weight loss, and had a good safety profile, would revolutionize the treatment of type II (non‐insulin‐dependent) diabetes. Two obesity management agents, orlistat and sibutramine, are expected shortly for the long‐term treatment of obesity. These agents have been shown to be effective in 1–2‐year‐long studies in obese, non‐diabetic patients. They produced significant improvements in weight loss compared with placebos. The efficacy of these obesity management agents has also been demonstrated in short‐term studies in patients with type II diabetes. As yet, however, few studies have investigated the long‐term effects of these treatments in diabetic patients. Obese patients with type II diabetes receiving 12 months of dexfenfluramine therapy showed greater reductions in weight, fasting blood glucose and HbA1c levels than the controls. A 1‐year study of orlistat treatment for patients with type II diabetes revealed substantial benefits in glycaemic control, even though weight loss was only moderate. A 1‐year treatment with orlistat also substantially prevented the conversion of impaired glucose tolerance into type II diabetes (conversion rate 2·6% in the orlistat group versus 10·4% in the placebo group). Encouraging results have also been reported from studies on orlistat and sibutramine in non‐diabetics, with beneficial effects seen for weight loss and other diabetes risk factors. Antiobesity pharmacotherapy therefore appears to offer a realistic option for the prevention of diabetes, although further studies are required to determine its efficacy.
Induction of rat uncoupling protein‐2 gene treated with tumour necrosis factor alpha in vivo
Authors: Masaki  , Yoshimatsu  , Kakuma  , Chiba  , Hidaka  , Tajima  , Kurokawa  , Sakata
Published: March 2003

Background

The cytokine tumour necrosis factor (TNF) α has been reported to induce metabolic abnormalities such as anorexia and thermogenesis. To investigate functional modulators of uncoupling protein‐2 (UCP2) gene expression, we examined the effects of TNF‐α on UCP2 mRNA expression in rats.

Methods

Mature male Wistar King A (WKA) rats at 10–11 weeks of age were treated with recombinant human TNF‐α at a dose of 0.6 nmol 100 g−1 body weight by intraperitoneal administration.

Results

TNF‐α treatment induced an increase in UCP2 mRNA expression in broadly distributed tissues including brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle, and an elevation of ob gene mRNA expression in WAT. After the TNF‐α treatment, an increase in plasma leptin concentration occurred in an ob gene‐dependent manner, accompanied by an anorectic effect.

Conclusion

The present results provide evidence for a new regulatory loop involving TNF‐α and UCP2, and add novel insights into the regulatory mechanisms of energy homeostasis.
Comparison of the effect of native glucagon‐like peptide 1 and dipeptidyl peptidase IV‐resistant analogues on insulin release from rat pancreatic islets
Authors: Siegel  , Scharf  , Gallwitz  , Mentlein  , Morys‐Wortmann  , Fölsch  , Schmidt
Published: March 2003

Background

Glucagon‐like peptide 1 (GLP‐1) stimulates insulin secretion and may improve glycaemic control in type 2 diabetes. Therapeutic use is limited by its rapid degradation, primarily by dipeptidyl peptidase IV.

Materials and methods

Five GLP‐1 analogues with alterations at cleavage positions were synthesized according to the Fmoc strategy and tested for metabolic stability by incubation with rat kidney membranes containing dipeptidyl peptidase IV activity. Their insulinotropic effect was compared in isolated rat pancreatic islets after 24 h maintenance in tissue culture. Ten islets per vial were incubated for 30 min; insulin was measured radioimmunologically. Each analogue was compared with GLP‐1 in the same experiment.

Results

All analogues were biologically active in isolated islets in the potency order da2d8 = da2 > d2d9 > da2ds8 > desamino. At 16.7 mmol L−1 glucose, GLP‐1 and GLP‐1 analogues altered as position 2, or 2 and 8 significantly (P < 0.05) increased insulin release at 10−9 mol L−1. N‐terminal modification of GLP‐1 confers resistance to dipeptidyl peptidase IV degradation in rat kidney membranes in vitro.

Conclusions

The analogues tested are biologically active and resistant to degradation by dipeptidyl peptidase IV. Their greater metabolic stability may help to realize the potential of GLP‐1 analogues in diabetes therapy.
Hyperosmolar saline induces airway resistance changes and neuropeptide release: a comparison with the effect of capsaicin, potassium and histamine
Authors: Högman  , Hageman  , Hua
Published: March 2003

Background

Healthy subjects do not show any bronchoconstricting response to inhalation of hypertonic saline, in contrast to subjects with symptoms of asthma. There is evidence indicating that these airway reactions may be related to stimulation of sensory nerves.

Materials and methods

We investigated the effects of hyperosmolar solutions on the changes in airway resistance as well as on release of neuropeptides from an isolated and perfused guinea pig lung model.

Results

We observed that hyperosmolar saline (HS), capsaicin, potassium and histamine induced different patterns of response in airway resistance and neuropeptide release. HS 3.6% induced a biphasic response in airway resistance. Initially a minor relaxation, 4 ± 1 cmH2O mL–1 min (P < 0.05), followed by a contraction, 22 ± 3 cmH2O mL–1 min (P < 0.01). This was associated with release of calcitonin gene‐related peptide (CGRP) 7.7 ± 1.9 fmol mL–1 g (P < 0.01), but not of neurokinin A (NKA), a known bronchoconstrictor. Mannitol, at the same osmolarity as HS 3.6%, did not elicit a change in airway resistance, CRGP or NKA release. Capsaicin at 10–6 mol L–1 and potassium at 70 mmol L–1 induced a profound increase in airway tone (50 ± 9 and 42 ± 8 cmH2O mL–1 min respectively; P < 0.01) and elevation of both CGRP (6.4 ± 1.9 and 3.9 ± 1.1 fmol mL–1 g respectively; P < 0.05) and NKA (3.3 ± 1.0 and 1.0 ± 0.2 fmol mL–1  respectively; P < 0.05). Histamine increased the airway resistance by 42 ± 8 cmH2O mL–1 min (P < 0.01) but had no effect on either CGRP or NKA release.

Conclusions

In healthy guinea pigs, hyperosmolar saline 3.6% initially caused relaxation of the airways followed by contraction and induced release of CGRP‐LI. This was not seen with mannitol at the same osmolarity as for the hyperosmolar saline.