bluuebunny/crossref_metadata_2025 huggingface dataset:
Age‐related cannibalism and horizontal transmission of a nuclear polyhedrosis virus in larval Spodoptera frugiperda
Authors: Chapman Jason W. , Williams Trevor , Escribano AnA. , Caballero Primitivo , Cave Ronald D. , Goulson DavE.
Published: March 2003

1. Experiments were carried out to investigate the incidence of cannibalism throughout the larval development of the noctuid moth Spodoptera frugiperda, and to examine the risk of infection from consuming conspecifics infected with a nuclear polyhedrosis virus (SfNPV).

2. Cannibalism was observed commonly even when food was not limiting, but occurred more frequently at low food quantities and/or high rearing densities. The sex of the larvae had no effect on the incidence of cannibalistic behaviour, however the probability of cannibalism occurring was affected by larval stage. The frequency of cannibalism was significantly higher among fifth‐ and sixth‐instar larvae than among earlier instars, and larvae were more likely to consume younger conspecifics than larvae of the same stage.

3. Fifth‐instar larvae offered fourth‐instar victims fed equally on healthy larvae, virus‐infected larvae (2 days post‐infection), uninfected corpses, and virus‐killed corpses (6 days post‐infection). Horizontal transmission of SfNPV was only recorded in larvae offered virus‐killed corpses, however, and total mortality in this treatment was only 32%.

4. In a similar experiment, fourth‐instar larvae avoided cannibalising virus‐killed corpses. Horizontal transmission of SfNPV was recorded in fourth‐instar larvae that consumed 2‐day post‐infected larvae. The low incidence of cannibalism observed in fourth‐instar larvae, however, suggests that this is unlikely to provide an important route for the transmission of SfNPV.
Can nectar properties explain sex‐specific flower preferences in the Adonis Blue butterflyLysandra bellargus?
Authors: Rusterholz Hans‐Peter , Erhardt A.N.dreas
Published: March 2003

1. Field observations in the Swiss Jura mountains showed that males and females of the bivoltine Adonis Blue butterflyLysandra bellargusRott. differed significantly in their flower visitation patterns.

2. In both generations, females visited a broader range of available nectar plants than did males. The specific flower visitation patterns of males and females were not affected by the general availability and abundance of potential nectar plant species during both flight periods, indicating high selectivity for nectar plants by both males and females.

3. In addition, the sexes differed in their nectar foraging behaviours: distances between successively visited flowers were significantly longer in males than in females, indicating that male and female butterflies have different foraging strategies.

4. Investigations of nectar characteristics showed that the sexes preferred flowers with different nectar compositions. Males of both generations preferred flowers with high proportions of sucrose and high amounts of total sugar, whereas females preferred flowers with high portions of glucose in their nectar, and, in the spring generation, flowers rich in amino acids.

5. Flowers visited exclusively by males or females in spring differed significantly in their amino acid composition.

6. This clear‐cut pattern did not hold for the autumn generation, most probably due to the limited availability of flowers.

7. The observed nectar foraging patterns underline the importance of adult feeding for longevity and reproduction in butterflies. The findings are particularly relevant for conservation, becauseL. bellargusis an increasingly threatened species in many European countries.
The effect of spatial scale on interactions between two weevils and their parasitoid
Authors: Norowi H. Mohd , Perry Joe N. , Powell W. , Rennolls K.
Published: March 2003

1. The effect of spatial scale on the interactions between three hymenopteran parasitoids and their weevil hosts was investigated. The parasitoid Mesopolobus incultus (Walker) parasitised Gymnetron pascuorum Gyll.; the parasitoids Entodon sparetus (Walker) and Bracon sp. parasitised Mecinus pyraster Herbst. Both of these weevils develop inside the seedhead of Plantago lanceolata L. but occupy different niches. Seedheads were sampled annually from 162 plants at each of two experimental sites consisting of a series of habitat patches of two distinct sizes. Data were analysed from three site‐years.

2. Parasitoid densities at each site‐year were closely related to the abundance of their respective weevil hosts. The overall proportion of hosts parasitised was more variable for M. incultus than for E. sparetus and Bracon sp.

3. Changes in spatial scale affected the variability of parasitoid densities. For M. incultus, there was generally a greater degree of additional heterogeneity for all increases of scale; for E. sparetus, this was true only at the largest scales; for Bracon sp., all components of variance were negative.

4. The rate of parasitism was related to host density in different ways at different spatial scales. Mesopolobus incultus exhibited inverse density dependence at the finest (seedhead) scale, direct density dependence at the intermediate (plant) scale, and density independence at the large (habitat area 729 m2) scale. Entodon sparetus showed no response to variation in host density at any spatial scale. Bracon sp. showed direct density dependence only at the intermediate and largest scales.

5. Parasitoids E. sparetus and Bracon sp. seemed able to detect more than one M. pyraster individual in seedheads with multiple host occupancy; a greater incidence of conspecific parasitoids than expected emerged from such seedheads.
Health food versus fast food: the effects of prey quality and mobility on prey selection by a generalist predator and indirect interactions among prey species
Authors: Eubanks Micky D. , Denno Robert F.
Published: March 2003

1. In order to understand the relative importance of prey quality and mobility in indirect interactions among alternative prey that are mediated by a shared natural enemy, the nutritional quality of two common prey for a generalist insect predator along with the predator's relative preference for these prey was determined.

2. Eggs of the corn earworm Helicoverpa zea (Lepidoptera: Noctuidae) were nutritionally superior to pea aphids Acyrthosiphum pisum (Homoptera: Aphididae) as prey for big‐eyed bugs Geocoris punctipes (Heteroptera: Geocoridae). Big‐eyed bugs survived four times as long when fed corn earworm eggs than when fed pea aphids. Furthermore, only big‐eyed bugs fed corn earworm eggs completed development and reached adulthood.

3. In two separate choice experiments, however, big‐eyed bugs consistently attacked the nutritionally inferior prey, pea aphids, more frequently than the nutritionally superior prey, corn earworm eggs.

4. Prey mobility, not prey nutritional quality, seems to be the most important criterion used by big‐eyed bugs to select prey. Big‐eyed bugs attacked mobile aphids preferentially when given a choice between mobile and immobilised aphids.

5. Prey behaviour also mediated indirect interactions between these two prey species. The presence of mobile pea aphids as alternative prey benefited corn earworms indirectly by reducing the consumption of corn earworm eggs by big‐eyed bugs. The presence of immobilised pea aphids, however, did not benefit corn earworms indirectly because the consumption of corn earworm eggs by big‐eyed bugs was not reduced when they were present.

6. These results suggest that the prey preferences of generalist insect predators mediate indirect interactions among prey species and ultimately affect the population dynamics of the predator and prey species. Understanding the prey preferences of generalist insect predators is essential to predict accurately the efficacy of these insects as biological control agents.
Bryophyte use by an insect herbivore: does the crane‐fly Tipula montana select food to maximise growth?
Authors: Smith R. M. , Young M. R. , Marquiss M.
Published: March 2003

1. Growth rates of immature invertebrates can be of profound importance to subsequent reproductive success in the adult stage. If diet selection in herbivores is a principal means of maximising growth and rate of development, individuals should select food of the highest quality.

2. If disparities are found between performance and preference, these may be the result of individuals balancing nutritional gain against other demands on their behaviour, such as a need for shelter. The responses of the crane‐fly herbivore Tipula montana Curtis (Diptera: Tipulidae) to a range of moss genera from an upland environment were investigated to determine whether diet selection was determined by food quality alone, as measured by its effect on larval growth and survival.

3. Larvae were reared individually on single moss genus diets, and their growth, development, and survival were measured. Each of the mosses supported growth and development although the mean weights achieved differed by a factor of two between food genera. In two‐choice preference experiments, individuals broadly chose bryophyte foods as expected from their quality. One notable exception was the moss Pleurozium schreberi, which gave the best growth performance but was among the least preferred.

4. The two methods of assessing preference gave different results: observations of larvae showed relatively greater selection for dense mosses than faecal pellet analysis. A strong dietary preference for an angiosperm, the sedge Carex bigelowii, over all mosses supported the interpretation that crane‐fly larvae benefit from bryophytes as a refuge, and that this factor may override dietary quality.
Multiple mating reduces longevity of females of the windmill butterfly Atrophaneura alcinous
Authors: Kawagoe Tetsuhiro , Suzuki Nobuhiko , Matsumoto Kazuma
Published: March 2003

1. The effects of successive matings by females on their performance were tested in laboratory experiments and field censuses for the windmill butterfly Atrophaneura alcinous.

2. In laboratory experiments, newly eclosed females were hand‐paired either once or twice successively. The number of eggs laid and the sucrose solution intake of these females were examined daily. Fecundity and sucrose solution intake did not differ significantly between once‐ and twice‐mated females, however the longevity of twice‐mated females was significantly shorter than that of once‐mated females, implying that successive matings involve a physiological cost.

3. The results of a mark–release–recapture census in a natural population also indicated that multiply mated females could not survive for as long as once‐mated females.

4. The results did not support the general consideration that multiple mating is beneficial to females in Lepidoptera. The importance of the timing of remating by females on the consequences of multiple mating is discussed.
Fitness costs and stability of resistance to Bacillus thuringiensis in a field population of the diamondback moth Plutella xylostella L.
Authors: Sayyed Ali H. , Wright Denis J.
Published: March 2003

1. The stability of resistance to Bacillus thuringiensis Crystal (Cry) toxins in highly and moderately resistant sub‐populations of a Plutella xylostella field population (SERD4) was compared under laboratory conditions. The relative rate of decrease in resistance was greater in a highly resistant Cry1Ac‐selected population than in moderately resistant Cry1Ab‐ and Cry1Ca‐selected populations.

2. The intrinsic rate of population increase (rm) was similar in all populations tested.

3. These results suggest that there are no obvious overall fitness benefits as the frequency of the resistance alleles is reduced.
Risk‐sensitive decisions during nesting may increase maternal provisioning capacity in the subsocial shield bug Parastrachia japonensis
Authors: Filippi Lisa , Hironaka Mantaro , Nomakuchi Shintaro
Published: March 2003

Abstract 1. Females of the monophagous shield bug Parastrachia japonensis Scott provision their nymph‐containing nests with high‐quality drupes of the single host tree, Schoepfia jasminodora, a resource that is poor and unstable, under an array of variable environmental constraints.

2. Although the number of drupes provisioned is correlated positively with enhanced nymphal development and survival, there is great variability in the number of drupes that females provide.

3. The ability to adjust behaviour and/or physiology, i.e. make risk‐sensitive decisions, should be adaptive for organisms such as P. japonensis that are confronted with extreme variability in food availability and in the conditions under which they must forage. To assess whether females of this species use risk‐sensitivity to improve their provisioning success, data on the parameters of provisioning activity obtained during a long‐term field study were analysed. The relationships between variation in three female‐controlled factors during nesting (nest site, active stage during the provisioning season, duration of provisioning activity) and the conditions of three environmental factors (drupe availability, intraspecific competition, weather) were examined. The relationships between all of these factors and provisioning capacity of females were investigated.

5. Nest site, intraspecific competition, and timing of provisioning activity only affected provisioning capacity when drupe availability was extremely good or bad or weather was particularly bad.

6. The findings suggest that females use risk‐sensitive decisions to increase provisioning capacity under extreme conditions of low and high drupe availability and inclement weather.
Dung beetles in a Central Amazonian rainforest and their ecological role as secondary seed dispersers
Authors: Andresen Ellen
Published: March 2003

Abstract1. The role of several factors that affect the composition of the dung beetle assemblages in an Amazonian rainforest was quantified, together with the effect of these factors on the role that dung beetles play as secondary seed dispersers.

2. A total of 61 dung beetle species was captured during 3360 h of trapping. During nocturnal trapping periods, more dung beetles, of larger mean size, and more species were captured per trap than during diurnal trapping periods.

3. During the rainy season, more dung beetle species were captured per trap than during the dry season, but the number of individuals and their mean size did not vary between seasons.

4. Bait size had a significant effect on the mean number of beetles and mean number of species but not on mean beetle size. As bait size increased from 5, 10, 25, to 50 g, more beetles and more species were captured per trap.

5. Between 6 and 73% of plastic beads, used as seed mimics, were buried by dung beetles at depths that ranged from 0.5 to 7 cm. Both the proportion of beads buried and burial depth decreased with increasing bead size, and increased with increasing amounts of dung surrounding each bead (5, 10, and 25 g).

6. The proportion of buried seeds for three species varying in size between 5 and 27 mm, increased with increasing dung beetle size, using beetles of seven sizes, varying between 10 and 25 mm.

7. Seeds surrounded by dung were buried more often and more deeply when placed on the forest floor during the late afternoon than when placed during the early morning. Seeds were also buried more often when placed on the forest floor during the rainy season than when placed during the dry season, but season had no effect on burial depth.

8. Forests in Central Amazonia hold a rich dung beetle community that plays an active role in secondary seed dispersal, and consequently in plant regeneration. The interaction between seeds and beetles is complex because it is affected by many factors.
Preference and performance are correlated in the spittlebug Aphrophora pectoralis on four species of willow
Authors: Craig Timothy P. , Ohgushi Takayuki
Published: March 2003

Abstract 1. There was a positive correlation between oviposition and feeding preferences and offspring performance in the spittlebug Aphrophora pectoralis Matsumura (Homoptera: Cercopoidea, Aphrophoridae) on four species of willow Salix sp. (Salicaceae) growing near Sapporo, Japan. Spittlebugs preferred rapidly growing shoots where performance was highest.

2. When the effects of shoot length were removed, egg densities on willow species were associated with offspring performance on three of four species. Egg densities and survival rates were low on Salix integra and Salix miyabeana. Survival rates were high on Salix sachalinensis, which had high egg densities, and Salix hultenii, which had low egg densities.

3. Aphrophora pectoralis formed mating aggregations almost exclusively on S. sachalinensis but then dispersed to other willow species to oviposit.

4. Nymphs dispersed from the oviposition site to feed on nearby shoots within the same plant but they did not disperse to other willow plants. Nymphs had the same preference for rapidly growing shoots as ovipositing females, so they were able to refine the maternal choice by moving to larger shoots near the shoot on which they had eclosed.

5. The spittlebugs were highly aggregated at all life stages so that even at high densities only a small proportion of the most vigorously growing shoots was utilised.
Parasitism by the mite Trombidium breei on four U.K. butterfly species
Authors: Conradt L. , Corbet S. A. , Roper T. J. , Bodsworth E. J.
Published: March 2003

Abstract 1.  The incidence of parasitism by larvae of the mite species Trombidium breei was reported in one population of the lycaenid butterfly Polyommatus icarus, four populations of the satyrine butterfly Maniola jurtina, one population of the satyrine butterfly Aphantopus hyperanthus, and two populations of the satyrine butterfly Pyronia tithonus, as well as on one specimen of the dipteran Alophorus hemiptera. A considerable proportion of butterflies (11‐50%) was infested in all study populations.

2. The pattern of infestation was examined in detail in M. jurtina. Males had a significantly higher incidence of infestation than females, and middle‐aged butterflies had a higher incidence of infestation than old or young butterflies. The incidence of infestation peaked in the middle of the flight season, and this seasonal effect was independent of the effect of butterfly age.

3. Using a model based on capture‐recapture data, it was estimated that a hypothetical ideal male M. jurtina that lives exactly the mean expected lifespan of 9‐10 days has an approximately 75% chance of becoming infested with mites at least once during its lifetime, a mean time to first infestation of 3‐4 days, and an average infestation persistence time of 2‐3 days.

4. Capture‐recapture data failed to show any effect of mite infestation on the lifespan or within‐habitat movement rate of M. jurtina.

5. In experiments in which individual butterflies were taken out of their normal habitat and released, M. jurtina and P. tithonus that were infested with mite larvae did not differ from uninfested individuals in the efficiency with which they returned to suitable habitat. Thus, parasitism by T. breei larvae had no detectable effects on flight performance or orientation ability.

6. The results suggest that trombidiid mite larvae have limited potential in the biological control of insect pests.
Intra‐guild predation relaxes natural enemy impacts on herbivore populations
Authors: Finke Deborah L. , Denno Robert F.
Published: March 2003

Abstract. 1. To investigate the role of intra‐guild predation in mediating the impact of the natural enemy complex on herbivore populations, a manipulative field experiment was conducted using uncaged plots (islets of Spartina cordgrass) on a North American salt marsh. The densities (moderate or low) of two invertebrate predators, the generalist wolf spider Pardosa littoralis and the specialist mirid bug Tytthus vagus, were manipulated in a 2 × 2 factorial design, and the resulting treatment effects on the population growth of their herbivorous prey, Prokelisia planthoppers, were assessed.

2. The abundance of wolf spiders on experimental islets was unaffected by the presence of mirid bugs, however the density of mirid bugs was influenced very negatively by the presence of the wolf spider.

3. The negative effect of the wolf spider on mirid bugs most probably resulted from the intra‐guild predation of mirids by spiders because planthopper limitation by the wolf spider alone was significantly greater than when both predators were present.

4. As a result of intra‐guild predation, planthopper population growth was positive in the presence of both predators, despite the fact that each predator alone promoted a decrease in planthopper population growth.

5. Notably, the occurrence of intra‐guild predation diminished top‐down impacts on planthopper populations in a relatively simple food web where strong top‐down effects were expected. This result, however, was limited to habitats on the marsh with simply structured vegetation lacking leaf litter.
Endogenous dopaminergic activity in Child–Pugh A cirrhosis: potential role in renal sodium handling and in the maintenance of clinical compensation
Authors: Sansoè  , Ferrari  , Baraldi  , Grisolia  , De Santis  , Villa  , Manenti
Published: March 2003

Background

We studied the main determinants of aldosterone secretion in a group of 20 patients with biopsy‐proven Child–Pugh A cirrhosis without previous ascites or diuretic consumption.

Methods

We evaluated the plasma levels of adrenocorticotrophic hormone (ACTH), active renin and aldosterone (both supine at 07.00 h and after 30 min of upright posture),and active renin and aldosterone responses 30 min and 60 min after the administration of metoclopramide, a dopamine DA2 antagonist (10 mg e.v.). Nine normal subjects were also submitted to the metoclopramide stimulation test.

Results

Compared with control subjects, the patients showed significantly greater incremental aldosterone responses both 30 min and 60 min after metoclopramide (+30 min: 157.5 ± 73.3 vs. 83.5 ± 32.2 pg mL−1, P < 0.003; +60 min: 142.1 ± 87.2 vs. 36.8 ± 39.0 pg mL−1, P < 0.001). We found significant positive correlations between amplitude of aldosterone response 30 min after metoclopramide and 24‐h urinary fractional excretion of sodium (r= 0.61, P < 0.01) and basal morning aldosterone levels (r= 0.69, P < 0.001).

Conclusions

The higher incremental aldosterone responses observed after metoclopramide in cirrhotic patients are expressions of increased dopaminergic activity in these patients compared with control subjects. Moreover, the correlation we found between the degree of dopaminergic activity and 24‐h urinary fractional excretion of sodium suggests a role for endogenous dopamine as a relevant mediator of natriuresis in cirrhosis, at least in patients with compensated disease.
Human liver glycogen metabolism assessed with a 13C‐enriched diet and a 13CO2 breath test
Authors: Tanis  , Van Den Berg  , Kroneman  , Wattimena  , Rietveld  , Nieland  , Swart
Published: March 2003

Background

Adequate liver glycogen stores to maintain hepatic glucose output by glycogenolysis in the post‐absorptive state are essential to prevent protein loss through gluconeogenesis. There are no simple techniques to monitor liver glycogen use.

Methods

In this study, we labelled liver glycogen with naturally 13C‐enriched carbohydrate and measured the pattern of 13CO2 excretion and the post‐prandial time during which oxidation of 13C‐labelled liver glycogen was demonstrable by 13CO2 enrichment in breath. Two experiments were performed in 24 healthy volunteers.

Results

In the first experiment we observed that breath 13CO2 enrichment returned to baseline values at 20.3 (SD 2.3, n = 12) hours post‐prandially, indicating exhaustion of the 13C‐labelled liver glycogen at that time. In a second experiment, breath 13CO2 enrichment in the early hours of the post‐prandial phase was studied. After a steep decline, which started 2–4 h after the last meal, the 13CO2 enrichment reached a plateau phase 6 h post‐prandially. This plateau phase lasted for about 6–8 h, suggesting steady‐state glycogenolysis during this period. The plateau phase was followed by a further decline in 13CO2 excretion, suggesting a gradually diminishing contribution of 13C‐labelled liver glycogen to substrate oxidation.

Conclusion

It is possible to label liver glycogen with a diet of naturally 13C‐enriched carbohydrate. The oxidation of the labelled liver glycogen can be monitored by measuring 13C‐enrichment in breath CO2.
Inhibition of platelet–vessel wall interactions by thromboxane receptor antagonism in a human in vitro system: potentiation of antiplatelet effects of aspirin
Authors: Escolar  , Albors  , Garrido  , Bioque  , Díaz Ricart  , Carretero  , Ordinas
Published: March 2003

Background

Pharmacological inhibition of arachidonic acid metabolism has proven therapeutically useful in the prevention of cardiovascular events.

Methods

We have investigated the ability of Bay u 3405, a synthetic thromboxane antagonist, to interfere with platelet aggregation and arachidonic acid metabolism. The antiplatelet action was also analysed in a perfusion system in which vascular subendothelium was exposed to circulating human blood (10 min; shear rate = 800 s−1). Platelet interactions were morphometrically analysed and results compared with those obtained in studies with blood from donors taking aspirin (acetylsalicylic acid, ASA) (500 mg day−1). The additional effect of Bay u 3405 on the antiplatelet action of ASA was also evaluated.

Results

Bay u 3405 caused a dose‐dependent inhibition of platelet aggregation induced by U46619 with a maximal effect at concentrations ≥ 0.01 μg mL−1. Higher concentrations (≥ 0.05 μg mL−1) also inhibited aggregations induced by ADP or collagen. Bay u 3405 did not interfere with platelet arachidonic acid metabolism. In perfusion studies, Bay u 3405 (0.01 μg mL−1) significantly decreased the total surface of the vessel covered by platelets (%CS = 18.7 ± 1.09 vs. 24.4 ± 1.94; P < 0.05) and the formation of large aggregates (%T = 7.5 ± 0.87 vs. 19.3 ± 1.61; P < 0.01). ASA treatment reduced platelet aggregate formation (%T = 13.7 ± 2.06; P < 0.05) but did not affect the total surface covered by platelets. The in vitro addition of Bay u 3405 to blood from ASA‐treated donors further reduced the formation of large aggregates (%T = 2.7 ± 0.79; P < 0.01 vs. ASA).

Conclusions

In vitro effects of Bay u 3405 on platelet function were superior to those observed with ASA. The thromboxane antagonism provided by Bay u 3405 further enhanced the inhibition of platelet aggregate formation found after ASA treatment.
Cytokine regulation of the acute‐phase protein levels in multiple myeloma
Authors: Bíró  , Domján  , Falus  , Jakab  , Cseh  , Kalabay  , Tarkovács  , Tresch  , Malle  , Kramer  , Prohászka  , Jákó  , Füst  , Császár
Published: March 2003

Background

Interleukin (IL) 6 has an important role in the regulation of acute‐phase proteins (APPs) during an acute‐phase response. We studied IL‐6 and other cytokines to determine if they regulate serum APP levels in the same way under the condition of the aberrant, long‐lasting ‘acute‐phase response’ that occurs in patients with chronic inflammation and cancer.

Methods

Serum levels of nine positive APPs [CRP, SAA, C1‐INH, Bf, C5, C8, C9, α1‐acidic glycoprotein (AGP) and haptoglobin] and two negative APPs [transferrin and α2‐HS glycoprotein (AHSG)] were measured using immunochemical methods in 59 multiple myeloma patients and in 72 healthy control subjects. Serum IL‐6 and tumour necrosis factor (TNF) α levels were determined by bioassays.

Results

IL‐6 was negatively correlated with five out of nine (C1‐INH, C8, C9, AGP and haptoglobin) positive APPs but positively correlated with C‐reactive protein (CRP). When patients with high and low IL‐6 serum concentration were compared, CRP levels were higher, AGP and haptoglobin levels were lower in the high‐ than in the low‐L‐6 group, whereas no significant difference between the two groups was found in levels of the other positive and negative APPs. TNF‐α levels were negatively correlated with transferrin and AHSG levels. No difference in the levels of positive APPs was observed between patients with low and high TNF‐α serum concentration. By contrast, levels of both transferrin and AHSG were significantly lower in the high‐ than in the low‐TNF‐α group.

Conclusions

These findings indicate that, except for regulation of the negative APPs by TNF‐α, the mechanism of APP regulation is different under the conditions of the short‐term and the chronic, long‐lasting ‘acute‐phase reaction’.
Tumour necrosis factor β alleles and hyperinsulinaemia in coronary artery disease
Authors: Braun  , März  , Winkelmann  , Donner  , Henning Usadel  , Badenhoop
Published: March 2003

Background

Hyperinsulinaemia and dyslipoproteinaemia are markers and risk factors for coronary artery disease (CAD) and non‐insulin‐dependent diabetes mellitus (NIDDM). We investigated the influence of a tumour necrosis factor β (TNF‐β) gene polymorphism on serum parameters related to these metabolic disorders in patients with CAD.

Methods

A total of 199 patients with CAD and 81 control subjects with angiographically normal coronary arteries were studied. A digestion of amplified DNA with NcoI revealed three fragment patterns: homozygosity for TNF‐β*1 or TNF‐β*2 and heterozygosity (TNF‐β*1/*2).

Results

Patients with CAD who had increased serum insulin or C‐peptide (fasting and after glucose load) were predominantly heterozygous for TNF‐β (72% vs. 47%) and less frequently homozygous for TNF‐β*2 (22% vs. 43%, P = 0.03).

Conclusion

This study demonstrates an association of TNF‐β alleles with the risk factor hyperinsulinaemia in CAD. Genomic variants of TNF‐β may therefore contribute to the complex susceptibility for the metabolic syndrome in patients with CAD.
Evidence for a role of T‐helper type 2 cytokines in the acquisition of human immunodeficiency virus syncytium‐inducing phenotype
Authors: Torres  , Medrano  , Rey  , Calderón  , Sánchez‐Quijano  , Lissen  , Leal
Published: March 2003

Background

The objective of the present study was to investigate the relationship between the serum cytokine pattern of T‐helper (Th) response and the acquisition of syncytium‐inducing (SI) human immunodeficiency virus type 1 (HIV‐1) variants in HIV‐1‐seropositive patients treated with antiretroviral drugs.

Methods

Serum cytokines of Th1/Th2 responses were analysed in a case–control study of 20 individuals selected from a cohort of HIV‐1‐infected patients without SI variants at entry, who developed or did not develop SI virus during a prospective follow‐up. A group of 10 patients with SI variants at study entry was also evaluated. Serum concentration of interferon (IFN) gamma, interleukin (IL) 2, IL‐4 and IL‐10 was evaluated by mean of a commercial enzyme immunoassay.

Results

Despite close matching for immunological (CD4+ cell count) and virological (p24 antigen, serum HIV viraemia) parameters, SI‐converting patients showed at baseline significantly lower serum levels of IL‐2 and higher concentrations of IL‐4 than those who remained persistently negative for SI variants. Shortly after the phenotype conversion, SI‐converting patients were characterized by significantly high serum concentration of IL‐4 and by low levels of IFN‐γ (Th2‐like pattern). Patients with SI phenotype at study entry featured lower mean levels of both IL‐4 and IL‐10, but mean IFN‐γ and IL‐2 values were higher, although the clinical and immunological baseline was also poorer and no statistical analysis could be applied.

Conclusion

Serum cytokine pattern of Th1/Th2 response differs between patients with NSI and SI phenotype. Our data strongly suggest that the Th2 cytokine pattern could be associated with the acquisition of the SI HIV‐1 phenotype.
Alterations in adhesion molecule (CD11b/CD18 and CD62L) expression on granulocytes after chemotherapy
Authors: Engervall  , Lundahl
Published: March 2003

Background

Infections during chemotherapy‐induced granulocytopenia constitute a major threat to patients with malignant disorders. The aim of this study was to evaluate whether circulating granulocytes after chemotherapy have a normal expression of adhesion molecules or if the granulocytes, in addition to being present in low number, also present signs of qualitative alterations.

Methods

We have investigated the time course of adhesion molecule expression (CD11b/CD18 and CD62L) and in vitro mobilization [responsiveness against N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) for CD11b/CD18] by flow cytometry in circulating granulocytes after chemotherapy in 12 patients with haematological malignancies. Blood samples for analysis were drawn before chemotherapy and at time points when granulocyte counts were < 0.5, 0.5–1.0 and > 1.0 × 109 L−1.

Results

The quantitative level, expressed as mean fluorescence intensity (MFI), of CD11b/CD18 was significantly higher and of CD62L significantly lower at granulocyte nadir than before chemotherapy. The in vitro responsiveness to fMLP was significantly reduced at the same time point. These alterations were restored to pretreatment values at the time of granulocyte count recovery. Granulocytes from patients with bacteraemia (n = 6) exhibited lower CD11b/CD18 MFI values after fMLP stimulation than non‐bacteraemic patients after granulocyte count recovery. In addition, the MFI of CD62L was significantly lower both before chemotherapy and after granulocyte recovery in the bacteraemic group.

Conclusion

Chemotherapy induces qualitative alterations in circulating granulocytes with respect to adhesion molecule expression and mobilization, and these alterations are more pronounced in patients with accompanying bacteraemia.
Determinants for the progression from impaired glucose tolerance to non‐insulin‐dependent diabetes mellitus
Authors: Nijpels
Published: March 2003

The World Health Organization distinguishes among non‐diabetic persons a form of glucose intolerance defined as impaired glucose tolerance (IGT). The main reason for considering IGT as a diagnostic entity is its prognostic value for the development of non‐insulin‐dependent diabetes mellitus (NIDDM). However, the use of one or two oral glucose tolerance tests (OGTT) for the definition of IGT and the large variability of the 2‐h glucose level may explain the wide range of the incidence rates reported for NIDDM in subjects with IGT. It is evident that the pathogenesis of diabetes is still poorly understood. Both insulin resistance and impaired function of the β‐cell are thought to be important contributing factors in the development of diabetes. The 2‐h post‐load glucose level from the OGTT is most powerful for the prediction of the development of NIDDM. In addition, a fasting hyperinsulinaemia and a low glucose removal rate, both reflecting insulin resistance, were found to be associated with a higher risk for the progression of NIDDM. In the San Antonio Study and in the Hoorn Study high fasting proinsulin levels, reflecting β‐cell dysfunction, were associated with progression to NIDDM. Lipid levels did not predict progression to NIDDM in most studies. A two‐step model for the development of NIDDM is hypothesized. The first step, the transition from normal to impaired glucose tolerance, is assumed to depend mainly on the presence of insulin resistance. The second step, progressing from IGT to diabetes, although accompanied by some further worsening of insulin resistance, is thought to be primarily dependent on the development of β‐cell dysfunction.
Beta‐blockers reduce the release and synthesis of endothelin‐1 in human endothelial cells
Authors: Garlichs  , Zhang  , Mügge  , Daniel
Published: March 2003

Background

Endothelins play an important role in cardiovascular diseases, and clinical trials have shown a reduction in endothelin levels after long‐term treatment of chronic heart failure with β‐adrenergic antagonists. It is not known, however, whether this effect is caused by haemodynamic changes associated with the use of β‐adrenergic antagonists or by direct interaction of β‐blockers with human endothelial cells. The aim of this study was to determine whether β‐adrenergic antagonists have an influence on endothelin‐1 (ET‐1) synthesis and release in human endothelial cells.

Methods

Pretreatment of cultured endothelial cells from human umbilical veins (HUVECs) with different concentrations of the non‐selective β‐blocker propranolol, the β1‐blocker metoprolol and the β1‐blocker and β2‐agonist celiprolol (all 10−7–10−4 mol L−1) was found to reduce ET‐1 production. This ET‐1‐reducing effect was even more pronounced in thrombin‐stimulated cells (10−5 mol L−1 of propranolol, metoprolol and celiprolol: 19% ± 5.8%, 25% ± 4% and 37% ± 5.2 % respectively).

Results

Quantitative reverse transcriptase polymerase chain reaction and Northern blotting confirmed an inhibitory effect of the β‐blocker on biosynthesis. Furthermore, the ET‐1‐reducing effect of propranolol, metoprolol and celiprolol was not due to a compensatory increase in prostacyclin and was not reversible by N‐nitro‐
L‐arginine.

Conclusion

The effect of β‐adrenergic antagonists on ET‐1 production of the endothelium may at least partially explain the efficacy of β‐blockers in the treatment of diseases such as advanced heart failure, essential hypertension as well as acute coronary syndromes.
Holotranscobalamin — a sensitive marker of cobalamin malabsorption
Authors: Lindgren  , Kilander  , Bagge  , Nexø
Published: March 2003

Background

No simple and reliable method of identifying patients with cobalamin malabsorption is available at present. The measurement of plasma holotranscobalamin, i.e. the metabolically active cobalamins bound to the transport protein transcobalamin, has been suggested as a means of fulfilling such criteria.

Design

We describe a method that directly quantifies cobalamins attached to transcobalamin. The method is evaluated in patients referred for gastrointestinal examination because of suspected cobalamin malabsorption.

Results

Of the 101 patients referred, all 48 with gastrointestinal conditions compatible with cobalamin malabsorption had plasma holotranscobalamin below 35 pmol L−1 (interval of 35–160pmol L−1). None of the patients with plasma holotranscobalamin above the lower reference limit had conditions compatible with cobalamin malabsorption.

Conclusion

The values obtained for plasma holotranscobalamin showed a better correlation with possible malabsorption than the values obtained for plasma cobalamins. The specificity of the test, however, needs to be elucidated further.
An angiotensin‐converting enzyme gene polymorphism suggests a genetic distinction between ischaemic stroke and carotid stenosis
Authors: Kostulas K. , Huang W.‐X. , Crisby M. , Jin Y.‐P. , He B. , Lannfelt L. , Eggertsen G. , Kostulas V. , Hillert J.
Published: March 2003

Background

Ischaemic cerebrovascular disease (ICVD) is a heterogeneous syndrome to which different genetic factors may contribute. We have investigated the distribution of alleles of the angiotensin‐converting enzyme (ACE) gene, which has been suggested to be of possible importance in ischaemic stroke or cardiovascular disease, in groups of patients with ischaemic stroke and carotid artery stenosis (CS).

Materials and methods

One hundred and thirty patients with ischaemic stroke and 68 patients with more than 50% stenosis of the internal carotid artery were investigated and compared with age‐ and sex‐matched healthy control subjects. Alleles of an insertion/deletion polymorphism of the ACE gene were determined by one‐stage polymerase chain reaction and visualized on agarose gels.

Results

There was a significant difference (P < 0.05) in the distribution of ACE alleles, homozygosity for the presumed susceptibility deletion allele being more common in patients with CS than in healthy control subjects. There was also a significant difference (P < 0.05) in patients with CS in comparison with matched ICVD patients without CS, both in allelic frequencies and in homozygosity for the deletion allele.

Conclusions

Our results indicate that the ACE gene polymorphism may be a risk factor for the development of CS. The observed difference in ACE allele distribution may be seen as evidence for a genetic distinction between ICVD and CS, two clinically related conditions, which further supports the hypothesis that genetic factors are of importance for this group of diseases.
Anti‐neutrophil cytoplasmic antibodies in a rat model of trinitrobenzenesulphonic acid‐induced liver injury
Authors: Orth  , Neurath  , Schirmacher  , Treichel  , Meyer zum Büschenfelde  , Mayet
Published: March 2003

Background

In sera from patients with autoimmune liver diseases, e.g. primary sclerosing cholangitis (PSC) and autoimmune hepatitis, anti‐neutrophil cytoplasmic antibodies (ANCAs) can be found. Until now, no animal model of ANCA induction in liver disease has been described. In this study, we describe a novel rat model of acute liver injury and subsequent ANCA production.

Materials and methods

The hapten reagent 2,4,6‐trinitrobenzenesulphonic acid (TNBS) was injected into the portal vein of female Lewis rats. Two experimental groups were studied: group A (TNBS/ethanol) received different TNBS concentrations; control animals of group B (ethanol) were injected with 10% (v/v) ethanol/0.9% (w/v) NaCl.

Results

A dose‐dependent acute necrotizing liver injury occurred after injection of TNBS. Histopathological examination revealed acute hepatic injury with confluent parenchymal necrosis, mild bile duct proliferation and periportal infiltration. The periportal infiltration consisted mainly of macrophages and T lymphocytes. ANCAs were found in an allogenic test system between 1 and 8 weeks after TNBS injection in 11 out of 28 (39%) TNBS‐treated rats (group A) and did not correlate with the extent of liver injury or TNBS dose. Autoantibody specificities of IgG type were directed against catalase (29%), myeloperoxidase (14%) and actin (7%), as detected by enzyme‐linked immunosorbent assay and Western blotting. Moreover, autoantibodies against the asialoglycoprotein receptor were observed. Peripheral blood mononuclear cells and spleen lymphocytes from TNBS‐treated rats were shown to produce ANCAs.

Conclusion

In summary, we were able to show that intraportal administration of the hapten reagent TNBS induces an acute necrotizing liver injury with subsequent ANCA production in Lewis rats. ANCA specificities were mainly directed against catalase, an autoantigen that has recently been identified in sera from patients with primary sclerosing cholangitis and autoimmune hepatitis. This animal model offers the opportunity to study the pathomechanisms of ANCA production in necrotizing liver injury.
L‐selectin in trauma patients: a marker for organ dysfunction and outcome?
Authors: Kerner  , Ahlers  , Spielmann  , Keh  , Bührer  , Gerlach  , Höfler  , Gerlach
Published: March 2003

Background

Systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are important factors affecting morbidity and mortality after trauma. Adhesion molecules, e.g. L‐selectin (CD62 L), play crucial roles in both conditions.

Patients and methods

In 51 multiple trauma patients, CD62 L surface expression on granulocytes, monocytes, lymphocytes, as well as sCD62 L plasma concentrations were determined during the first 6 days after trauma, starting at the site of accident. Clinical parameters were severity of injury scores (ISS, APACHE II), requirement of red blood cell transfusion, acute lung or liver failure, development of MODS or SIRS, early (≤ 6 d) or late (> 6 d), and outcome.

Results

CD62 L expression was reversibly elevated on granulocytes, T cells and monocytes in comparison with initial values. sCD62 L plasma concentrations did not show temporal variations but were depressed throughout observation period, in comparison with healthy controls. Lung failure within the first 6 days was associated with increased CD62 L expression on monocytes and B cells on admission and increased sCD62 L concentrations after 12 and 24 h. Patients with more severe injuries (APACHE II > 20 points) had higher sCD62 L concentrations after 24 h. Non‐survivors had decreased sCD62 L (on admission) and T‐cell CD62 L expression (after 4 h). Patients with early MODS or SIRS showed increased monocyte CD62 L expression after 6 days.

Conclusions

In multiple trauma patients, severe organ dysfunction is associated with altered CD62 L expression on leukocytes and circulating sCD62 L plasma concentrations. However, the obvious complexity of the pattern currently restricts use of CD62 L quantitation for clinical purposes.
JNK and c‐Jun but not ERK and c‐Fos are associated with sustained neointima‐formation after balloon injury
Authors: Watson  , Herdegen  , Buschmann  , Denger  , Wende  , Jahn  , Kreuzer
Published: March 2003

Background

Formation of neointima after balloon angioplasty is regulated via inducible transcription factors (ITF), such as c‐Jun and c‐Fos, depending on mitogen activated protein (MAP) kinases, which have been shown to be activated after balloon injury. The precise localization of activated MAP‐kinases and concomitant expression of transcription factors in the vessel wall remains to be elucidated. We have now studied the localization and time‐dependent expression of MAP‐kinases together with corresponding ITFs in the rat carotid angioplasty model.

Design

Animals were sacrificed at 0.5, 6 and 24 h and 3, 5, 7, 14 and 28 days after injury. Cryocut sections were stained using antibodies directed against c‐Jun, phosphorylated c‐Jun, c‐Fos, c‐Jun amino‐terminal kinase (JNK), extracellular signal related kinase (ERK), von Willebrand factor, ki67 antigen, and α‐actin.

Results

c‐Jun expression was strongly induced in smooth muscle cells (SMC) 30 min after injury and remained upregulated for 24 h, thereafter dropping to basal levels at day 3. Re‐expression was observed at day 7 and 14 but not day 28. Expression patterns of JNK and phosphorylated c‐Jun were highly congruent to that of c‐Jun. In contrast, c‐Fos expression was restricted to 30 min and, less pronounced than c‐Jun and JNK, was visible after 7 days. Also, its expression was congruent with the presence of ERK.

Conclusions

These findings demonstrate a clear association between MAP‐kinases and their transcription factor substrates in vivo with a predominant association of JNK and c‐Jun with sustained SMC proliferation.
Assessment of human muscle glycogen synthesis and total glucose content by in vivo13C MRS
Authors: Van Den Bergh  , Tack  , Van Den Boogert  , Vervoort  , Smits  , Heerschap
Published: March 2003

Background

Obesity is often accompanied by a decreased ability of insulin to stimulate glucose uptake and glycogenesis in skeletal muscle. The aim of this study was to investigate the rate of glycogen formation and of muscular glucose content in relation to insulin sensitivity under euglycemic conditions.

Materials and methods

We applied a hyperinsulinemic (430 pmol m−2 min−1) euglycemic clamp with infusion of 20% glucose (30% enriched with 13C‐1‐glucose) to 8 subjects with a wide range of insulin sensitivities. Glycogen and glucose levels were monitored simultaneously by in vivo13C MRS of the calf muscle on a clinical MR system at 1.5T field strength.

Results and conclusions

Glycogen synthesis rate showed a strong correlation with whole body glucose uptake during the clamp (r = 0.93, P < 0.01). With the use of 13C MRS, total muscular glucose content could be determined in vivo, and showed a positive, linear correlation with glycogen synthesis rate (r = 0.85, P < 0.01). 13C MRS provides important information regarding in vivo insulin action. Preliminary results indicate that the glycogen synthesis rate improves after treatment with troglitazone.