bluuebunny/crossref_metadata_2025 huggingface dataset:
Three views on the RAE Design and the computer. Fundamental questions of design
Authors: Price Sam
Published: May 2003

The two articles on canopies in the last issue of arq (6/3, pp214–229 and 230–245) make interesting reading. The briefs must have been quite similar – but what a difference in approach to design! Both canopies had to provide temporary cover to a fairly small area, during the summer, at about the level of a normal storey height, and both had to be easy to put up and take down in a fairly short time. The canopy in a courtyard in Amsterdam had to relate to the building and was originally intended to partly surround a tree [1]; the canopy for the Chelsea Flower Show was free-standing in the garden [2]. But the differences in situation do not account for the differences in design approach. The only common points here were that both were designed by a collaborative effort between architect and engineer – surely the only way to design something like this – and for both the starting point seemed to be, by implication, the rejection of anything totally regular, and the need to be innovative.
HABIT FORMATION AND GOVERNMENT SPENDING IN A SMALL OPEN ECONOMY
Authors: Karayalçin Cem
Published: May 2003

The paper studies the effects of an expansionary fiscal policy in a general equilibrium model of a small open economy. Households are assumed to possess habit-forming, endogenous rates of time preference. In response to fiscal shocks, the model generates cyclical endogenous persistence and procyclical time paths for consumption, employment, and investment, as well as a countercyclical path for the current account. Furthermore, fiscal shocks are shown to have positive long-run effects on output and negative long-run effects on consumption.
Transfer in bilingual first language acquisition
Authors: MÜLLER NATASCHA
Published: May 2003

Much research on bilingual first language acquisition has stressed the role of the dominant or preferred language when the two languages have some influence on one another. The present paper tries to look at transfer or interference from the perspective of the input the child is exposed to. Transfer will be argued to occur in those domains of the grammar where the language learner is confronted with ambiguous input. The bilingual child may, as a relief strategy, use parts of the analysis of one language in order to cope with ambiguous properties of the other. Ambiguity of input is crucial and will be evaluated through a comparison with monolingual language acquisition: if monolingual children have problems with the language material in question, it may be suggested that the input contains evidence for more than only one grammatical analysis. A quantitative difference between monolingual and bilingual language acquisition will be interpreted as evidence in favor of cross-linguistic influence in bilingual language development. The paper reviews longitudinal studies on the acquisition of word order in German subordinate clauses.
Transfer and language mode
Authors: GROSJEAN FRANÇOIS
Published: May 2003

Natascha Müller's proposal to view transfer as a relief strategy used by bilingual learners to cope with problematic input is very interesting and has far-reaching consequences for theories of bilingual language acquisition. The author makes a strong case for the fact that bilingual children transfer parameter values from the language presenting unambiguous input to the other “puzzling language”. In what follows, I will not question the main thrust of her argument. Rather I will return to the definitions that have been proposed for transfer in the literature and show that they are usually too broad. I will then propose that anyone interested in studying transfer must take into account the language mode the language learner or bilingual subject is in when being studied, and I will end by showing the consequences that this may have if it is not done. Natascha Müller's main argument is not affected by the language mode factor but the quantitative difference she finds between monolingual and bilingual children could be.
Conceptual representation in bilingual memory: Effects of concreteness and cognate status
in word association
Authors: VAN HELL JANET G. , DE GROOT ANNETTE M. B.
Published: May 2003

A word association experiment examined conceptual representation in bilingual memory. Dutch-English bilinguals associated twice to nouns and verbs that varied on concreteness and cognate status, once in the language of the stimuli (within-language), and once in the other language (between-language). Within- and between-language associations for concrete words and for cognates were more often translations of one another than those for abstract words and noncognates, and nouns evoked more translations than verbs. In both within- and between-language association, retrieving an associate was easier to concrete than to abstract words, to cognates than to noncognates, and to nouns than to verbs. These findings suggest that conceptual representation in bilingual memory depends on word-type and grammatical class: concrete translations, cognates, and noun translations more often share, or share larger parts of, a conceptual representation than abstract translations, noncognates, and verb translations. The results are discussed within the framework of distributed memory representation.
Romantische Männer und realistische Frauen: Geschlechtsunterschiede in Beziehungskognitionen
Authors: Hassebrauck Manfred
Published: May 2003

Zusammenfassung: In drei Studien werden Geschlechtsunterschiede in den Merkmalen, die eine gute Paarbeziehung kennzeichnen, sowie in der Verarbeitung beziehungsrelevanter Informationen untersucht. Studie 1 zeigt, dass Frauen mehr auf Merkmale, die Reziprozität und Kommunikation betreffen, Männer hingegen mehr auf Sexualität und Spaß in der Beziehung Wert legen. Studie 2 weist darauf hin, dass Merkmale der Qualität einer Beziehung im kognitiven System von Frauen schneller verfügbar sind, und Studie 3 zeigt, dass Frauen Beziehungsinformationen genauer verarbeiten, als Männer das tun.
Zur Frage einer Angstauslösung durch ein Angstinterview bei Vorschulkindern
Authors: Kiefert Ulrike , Lohaus Arnold , Frebel Christina , Becker Birgit
Published: May 2003

Zusammenfassung: Es wird der Frage nachgegangen, ob die Durchführung eines Angstinterviews bei Vorschulkindern negative Emotionen erzeugt. Bei 120 Kindern wurde ein Interview zur Erhebung typischer Kinderängste durchgeführt. Die Kinder wurden gebeten, vor und nach der Interviewdurchführung ein Bild von sich selbst zu malen. Die Bilder wurden über das Internet 137 Studierenden in einer Zufallsreihenfolge präsentiert, wobei mit fünfstufigen Ratingskalen zu beurteilen war, wie stark in den Bildern Ängstlichkeit, Traurigkeit und Unzufriedenheit zum Ausdruck kam. Zusätzlich sollte das Entwicklungsniveau der Kinderzeichnungen eingeschätzt werden. Ergänzend wurden weitere Selbst- und Fremdbeurteilungen zur Ängstlichkeit (durch die Interviewerinnen, die Eltern und die Erzieherinnen) erhoben. Nach der Interviewdurchführung zeigt sich in den Kinderzeichnungen eine signifikante Zunahme der eingeschätzten Ängstlichkeit, Traurigkeit und Unzufriedenheit. Die Effekte bleiben auch dann bestehen, wenn das eingeschätzte Entwicklungsniveau als Kovariate berücksichtigt wird. Die Ergebnisse werden hinsichtlich ihrer Implikationen für die Gestaltung von Datenerhebungen im Kindesalter diskutiert.
Basal cell carcinoma with tricholemmal (at the lower portion) differentiation within seborrheic keratosis
Authors: Misago Noriyuki , Satoh Toshimi , Narisawa Yutaka
Published: May 2003

Background:  Recent genetic investigations support the idea that basal cell carcinoma (BCC) is trichoblastic carcinoma. However, it is generally thought that clear cell basal cell carcinoma is a result of degeneration rather than tricholemmal differentiation.

Methods:  We report a case of BCC, with clear cell components, that developed within seborrheic keratosis, with histopathological and immunohistochemical findings.

Results:  The clear cell components in the present case showed the following four characteristics: (i) at the periphery of the aggregations, columnar clear cells were aligned in a palisade along a well‐defined basement membrane; (ii) the nuclei of the columnar clear cells were at the pole opposite the basement membrane; (iii) the clear cells contained glycogen; (iv) in the aggregations with clear cell components, there was diffuse positive staining for cytokeratin 7 (CK7) (OV/TLR/30), but only the inner region stained positive for CK17. These four characteristics are comparable to those of the lower portion of normal outer root sheath. In addition, the BCC in the present case was partly composed of squamous cells that contained glycogen and were selectively positive for CK17 – features similar to those of squamous cells in normal outer root sheath.

Conclusions:  Some clear cell BCCs are simply the result of degenerative change, but other clear cell BCCs may be the result of tricholemmal (at the lower portion) differentiation.
Idiosyncratic relationships between pond invertebrates and environmental, temporal and patch‐specific predictors of incidence
Authors: Jeffries Michael James
Published: May 2003

The incidence of eight species of microcrustacea and seven species of Dytiscidae (adults) was recorded from 30 small, temporary pools, in January and early summer, over six years. Incidence of each species, both in January and in summer, was modelled using logistic regression. Three categories of predictor variables were included in the models. Firstly systematic environmental variables; length of previous summer's dry phase, inter‐pond links caused by flooding, distance between ponds and macrophyte structural density. Secondly temporal factors; year and previous incidence. Thirdly individual ponds, representing patch‐specific effects. Logistic regression provided effective models of incidence for most species. However individual species varied in the factors that provided significant prediction of presence and absence. Systematic, temporal and patch‐specific predictors were all significant predictors for different species of both microcrustacea and Dytiscidae. No single factor dominated most models. Individual factors showed positive or negative relationships with incidence with different species. Length of previous summer dry‐phase was the most common predictor for microcrustacea and beetles in January. Summer models were more varied; length of previous dry phase and flood linkage between ponds and macrophyte density were significant predictors in many models, year and distance less important. Patch‐specific predictors were significant for five of the microcrustacea and four of the beetles. The results suggest that individual species show idiosyncratic responses to systematic, temporal and patch‐specific factors, rather than most species responding in a similar way to one or two dominant influences.
Species–area relationships of butterflies in Europe and species richness forecasting
Authors: Ulrich Werner , Buszko Jarosław
Published: May 2003

Species–area relationships (SARs) of European butterfly species (Rhopalocera) appear to follow power functions with Mediterranean butterflies having a much higher slope value (z=0.49) compared to the slope for the northern and eastern European countries (z=0.10). A simulated process of species extinction by a stepwise density dependent random elimination of species affected species–area patterns differently. For Mediterranean countries SAR slopes decreased, for other European countries slopes increased during the extinction process. Comparisons of species numbers before and after extinction with those predicted by a classical SAR approach differed widely and revealed that SARs are not able to predict future species numbers at local scales. For Mediterranean countries the classical SAR approach underestimated the number of species remaining after simulated extinction, for all other European countries SARs highly overestimated species numbers. These contrasting patterns indicate that changes in SAR patterns do not unequivocally point to changes in species diversity or community structure as assumed by current theory. On the other hand, the results strongly indicate that simplified applications of SARs for forecasting might give misimpressions about species loss and future biodiversity if the initial community structure, especially relative densities and numbers of species with restricted range size, are not taken into account.
Population density and species composition of moss‐living tardigrades in a boreo‐nemoral forest
Authors: Jönsson K. Ingemar
Published: May 2003

This study investigates for the first time the tardigrade fauna in a variety of different mosses from a coniferous forest and an adjacent clear‐cut area in southern Sweden. Tardigrades were found in a majority of the samples. Sixteen species were recorded, of which the cosmopolitan species Macrobiotus hufelandi was the far most common. Some mosses, particularly species with “wefts” growth form, contained more tardigrades than other mosses, indicating that growth form may have an impact on tardigrade abundance. Mosses of the same species collected from a forest and from a clear‐cut, respectively, did not show a general trend in the overall abundance of tardigrades, but the forest tended to contain more species. Five species of tardigrades (Murrayon dianae, Isohypsibius sattleri, Platicrista angustata, Diphascon belgicae and Diphascon pingue) never previously reported from Sweden were recorded.
The Inhibitory Effect of Androgen and Sex‐Hormone‐Binding Globulin on the Intracellular cAMP Level and Tyrosinase Activity of Normal Human Melanocytes
Authors: Tadokoro Taketsugu , Rouzaud Francois , Itami Satoshi , Hearing Vincent J. , Yoshikawa Kunihiko
Published: May 2003

The effect of androgens on human melanocytes has not been well clarified. We studied the effects of androgens on normal human melanocytes in the presence or absence of sex‐hormone‐binding globulin (SHBG), which complexes with those hormones. Immunohistochemically, testosterone and SHBG co‐localized on the cell membrane. Androgens such as testosterone, 5α‐dihydrotestosterone, and methyltrienolone (R1881, a potent synthetic androgen), reduced intracellular cAMP levels after treatment with SHBG, but hydrocortisone had no effect. We also found that testosterone and R1881 slightly suppressed tyrosinase activity in melanocytes when treated with SHBG, although they had no effect on the expression of tyrosinase at the transcriptional or translational level, as measured by semi‐quantitative reverse transcriptase‐polymerase chain reaction and by Western blot analysis, respectively. Our results suggest that androgens may modulate tyrosinase activity at the posttranslational level through the cell membrane signaling pathway.
Melanin as a Target for Melanoma Chemotherapy: Pro‐oxidant Effect of Oxygen and Metals on Melanoma Viability
Authors: Farmer Patrick J. , Gidanian Shirley , Shahandeh Babbak , Di Bilio Angel J. , Tohidian Nilou , L. Meyskens Frank
Published: May 2003

Melanoma cells have a poor ability to mediate oxidative stress, which may be attributed to constitutive abnormalities in their melanosomes. We hypothesize that disorganization of the melanosomes will allow chemical targeting of the melanin within. Chemical studies show that under oxidative conditions, synthetic melanins demonstrate increased metal affinity and a susceptibility to redox cycling with oxygen to form reactive oxygen species. The electron paramagnetic resonance (EPR)‐active 5,5′‐dimethyl‐pyrollidine N‐oxide spin adduct was used to show that binding of divalent Zn or Cu to melanin induces a pro‐oxidant response under oxygen, generating superoxide and hydroxyl radicals. A similar pro‐oxidant behaviour is seen in melanoma cell lines under external peroxide stress. Melanoma cultures grown under 95% O2/5% CO2 atmospheres show markedly reduced viability as compared with normal melanocytes. Cu‐ and Zn‐dithiocarbamate complexes, which induce passive uptake of the metal ions into cells, show significant antimelanoma activity. The antimelanoma effect of metal‐ and oxygen‐induced stress appears additive rather than synergistic; both treatments are shown to be significantly less toxic to melanocytes.
Enhancement of α2‐adrenoceptor‐mediated vasoconstriction by the thromboxane‐mimetic U46619 in the porcine isolated ear artery: role of the ERK–MAP kinase signal transduction cascade
Authors: Bhattacharya B , Roberts R E
Published: May 2003

α2‐Adrenoceptor‐mediated contractions in porcine blood vessels can be enhanced in the presence of the thromboxane‐mimetic U46619, and forskolin. The aim of this study was to determine the role of U46619 in the enhanced contractions, and to determine whether signalling through the ERK–MAP kinase pathway is involved.

Responses to the α2‐adrenoceptor agonist UK14304 (1 μM) were increased from 22±3% of the response to 60 mM KCl to 68±12% (n=8, mean±s.e.m.) in the presence of a low concentration of U46619 (<20% of the 60 mM KCl response).

Both the direct and the U46619‐enhanced UK14304 responses were inhibited by 50 μM PD98059, an inhibitor of the ERK–MAP kinase pathway. UK14304‐induced contractions were associated with an increase in ERK2 phosphorylation, indicating an increased activity. In the presence of U46619, there was an enhanced phosphorylation of ERK2. U46619 on its own had no effect on ERK phosphorylation.

Both the direct and enhanced UK14304 contractions were inhibited in the absence of extracellular calcium. These conditions also prevented the increase in ERK2 phosphorylation. This indicates a role for calcium influx in the enhanced contractions.

In conclusion, this study demonstrates that precontraction with the thromboxane‐mimetic U46619 enhances α2‐adrenoceptor‐mediated vasoconstriction through the enhancement of the ERK–MAP kinase pathway, and influx of extracellular calcium.

British Journal of Pharmacology (2003) 139, 156–162. doi:10.1038/sj.bjp.0705208
Activation of ATP‐dependent potassium channels is a trigger but not a mediator of ischaemic preconditioning in pigs
Authors: Schulz Rainer , Gres Petra , Heusch Gerd
Published: May 2003

Activation of ATP‐dependent potassium channels (KATP) is involved in ischaemic preconditioning (IP). In isolated buffer‐perfused rabbit hearts, activation of mitochondrial KATP – through a generation of free radicals – acted as a trigger rather than a mediator of IP; the isolated buffer‐perfused heart preparation, however, favours free radical generation. In contrast, in vivo studies in rats and dogs suggested that activation of KATP acts as a mediator of IP's protection. A detailed analysis on the role of KATP in IP's protection in vivo by varying the time and dose of KATP blocker administration is, however, lacking.

In 54 enflurane‐anaesthetized pigs, the left anterior descending coronary artery was perfused by an extracorporeal circuit. Infarct size (IS, %, TTC) following 90 min sustained low‐flow ischaemia and 120 min reperfusion was 26.6±3.5 (s.e.m.) (n=8). IP with one cycle of 10 min ischaemia and 15 min reperfusion reduced IS to 6.5±2.1 (n=7, P<0.05). Blockade of KATP with glibenclamide (0.5 mg kg−1 i.v., 50 μg min−1 continuous infusion) starting 10 min before or immediately following the preconditioning ischaemia abolished IS reduction by IP (20.7±2.7, n=7 and 21.9±6.6, n=6, respectively) while having no effect on IS per se (22.2±5.2, n=7), supporting a trigger role of KATP in IP. In contrast, starting glibenclamide following the preconditioning ischaemia 10 min prior to the sustained ischaemia did not prevent IS reduction by IP (3.7±2.3, n=6), even when its bolus dose was increased to 1.5 mg kg−1 (26.6±3.8 with IP vs 37.5±2.9 without IP; n=7 and 6 respectively, P<0.05), thereby refuting a mediator role of KATP in IP.

In conclusion, activation of KATP in the immediate reperfusion following the preconditioning ischaemia is pivotal for triggering IP.

British Journal of Pharmacology (2003) 139, 65–72. doi:10.1038/sj.bjp.0705225
Different molecular sites of action for the KATP channel inhibitors, PNU‐99963 and PNU‐37883A
Authors: Cui Yi , Tinker Andrew , Clapp Lucie H
Published: May 2003

We investigated the mechanism of action of two novel nonsulphonylurea ATP‐sensitive potassium channel (KATP) inhibitors, PNU‐99963 and PNU‐37883A, on four types of cloned KATP channels.

Whole‐cell currents were recorded in a symmetrical potassium (140 mM) gradient in HEK‐293 cells stably expressing Kir6.2/SUR1, Kir6.2/SUR2A, Kir6.2/SUR2B or Kir6.1/SUR2B.

PNU‐99963 potently inhibited the four KATP channel clones. The concentration at which half‐maximum current was inhibited (IC50) was 66, 41, 43 and 11 nM for Kir6.2/SUR1, Kir6.2/SUR2A, Kir6.2/SUR2B and Kir6.1/SUR2B, respectively. In contrast, PNU‐99963 up to a concentration of 3 μM had no significant effect on current generated in HEK‐293 cells by transiently expressing Kir6.2Δ26, a C‐terminal truncated pore‐forming subunit of Kir6.2.

PNU‐37883A inhibited four types of KATP channels, but to different extents. Inhibition of the putative smooth muscle KATP channel types, Kir6.2/SUR2B (IC50; 15 μM) and Kir6.1/SUR2B (IC50; 6 μM), was significantly greater than inhibition of either the pancreatic β cell or cardiac KATP channel clones. Moreover, PNU‐37883A significantly inhibited currents generated by expressing Kir6.2Δ26 alone, with an IC50 of 5 μM, which was significantly increased to 38 μM when Kir6.2Δ26 was expressed with SUR2B.

In conclusion, two structurally different nonsulphonylurea compounds, PNU‐99963 and PNU‐37883A, inhibit KATP channels via different mechanisms, namely through the sulphonylurea receptor (SUR) and the pore‐forming subunits, respectively, although SUR2B reduced the inhibitory effect of PNU‐37883A. While PNU‐99963 potently inhibits all the four cloned KATP channels, PNU‐37883A has a degree of selectivity towards both smooth muscle KATP channels, but could not discriminate between them.

British Journal of Pharmacology (2003) 139, 122–128. doi:10.1038/sj.bjp.0705228
CC chemokine receptor 1 enhances susceptibility to Leishmania major during early phase of infection
Authors: Rodriguez‐Sosa Miriam , Rosas Lucia E , Terrazas Luis I , Lu Bao , Gerard Craig , Satoskar Abhay R
Published: May 2003

CC chemokine receptor 1 (CCR1) is expressed on the surfaces of monocytes, lymphocytes, neutrophils and eosinophils. CC chemokine receptor 1 not only regulates leucocyte chemotaxis, but also plays a role in the regulation of Th1/Th2 cytokine responses. To determine the role of CCR1 in regulation of immune response during Leishmania major infection, we analysed the course of cutaneous L. major infection in CCR1‐deficient C57BL/6 mice (CCR1−/−) and compared with similarly infected wild‐type mice (CCR1+/+). Following L. major infection, CCR1−/− mice developed significantly smaller lesions containing fewer parasites than CCR1+/+ mice. Furthermore, the severity of the inflammation as assessed by the degree of leucocyte infiltration at the site of infection was similar in CCR1+/+ and CCR1−/− mice. Although both groups developed significant antibody responses following L. major infection, CCR1−/− mice produced significantly lower IgE. On day 20 postinfection, LmAg‐stimulated lymph node cells from L. major‐infected CCR1+/+ and CCR1−/− mice produced comparable levels of IL‐12 and IFN‐γ, but those from CCR1−/− mice produced significantly less IL‐4 and IL‐10. By day 70, lymph node cells from both CCR1+/+ and CCR1−/− mice produced significant amounts of IL‐12 and IFN‐γ but low IL‐4. At both time points, the draining lymph nodes from CCR1+/+ and CCR1−/− mice contained similar number of leucocytes. These results demonstrate that CCR1 plays a role in pathogenesis of cutaneous L. major infection. Moreover, they also indicate that CCR1 exacerbates L. major infection in C57BL/6 mice by up‐regulating Th2‐like response rather than inhibiting Th1 development or/and influencing leucocyte chemotaxis.
Emergency contraception: Knowledge, attitude, and practices among health care providers in North India
Authors: Tripathi Reva , Rathore Asmita Muthal , Sachdeva Jyoti
Published: May 2003

Aims:  The present study was conducted to assess knowledge, attitude, and practice of emergency contraception in health care providers and users in North India.

Methods:  A survey was carried out with the help of a predesigned questionnaire comprising of two groups of clients (abortion seekers at Family Welfare center, and non‐medical college students (prospective clients)); and 4 groups of health care providers (gynecologists, general practitioners, paramedical workers, and medical students).

Results:  Practically none of the clients were familiar with the concept of emergency contraception and so the rest of the information could not be obtained from them and hence this was excluded from further analysis. Many providers (84.8% gynecologists, 41.0% general practitioners, 2.7% paramedical workers, and 64.4% medical students) were vaguely familiar with the concept of emergency contraception, very few knew accurately about timing and doses. The majority of these thought it to be an essential component of contraceptive services but preferred distribution through health care providers only. The practice of emergency contraception as reported in the present survey was inconsistent. Yuzpe regimen was the most commonly used method and nausea/vomiting were the commonest side‐effects. The question of efficacy of emergency contraception was not answered reliably by the health care providers.

Conclusions:  Awareness about emergency contraception among the general population and paramedical workers studied is practically nonexistent. Precise knowledge about emergency contraception among doctors (both gynecologists and general practitioners) is also inadequate. Prescription practices can improve by generating demand and training of health care providers.
Six hourly vaginal misoprostol versus intracervical dinoprostone for cervical ripening and labor induction
Authors: Agarwal Nutan , Gupta Anjali , Kriplani Alka , Bhatla Neerja , Parul
Published: May 2003

Aim:  Prospective clinical trials were conducted to assess the safety and efficacy of 6‐hourly vaginal misoprostol versus intracervical dinoprostone for induction of labor.

Methods:  A total of 120 pregnant women requiring induction of labor were recruited. Cases were randomized to receive either 50 µg vaginal misoprostol 6 hourly (group I, n = 60) or 0.5 mg intracervical dinoprostone 6 hourly (group II, n = 60). Outcome measures, such as change in Bishop's score, need of oxytocin, induction delivery interval; complications like tachysystoly, hyperstimulation, abnormal fetal heart rate, and meconium passage were compared between two groups. Statistical analysis was performed by Wilcoxan's Rank sum and Student's t‐test.

Results:  Bishop score rise, after 6 h of initiation of therapy was significantly higher in the misoprostol group than dinoprostone, 2.98 ± 2.57 versus 2.05 ± 1.83 (P = 0.04). The need of oxytocin augmentation was reduced in misoprostol versus dinoprostone group, 16.6% versus 78.3% (P = <0.001). Induction delivery interval was shorter in misoprostol; 12.8 ± 6.4 h versus 18.53 ± 8.5 h in dinoprostone group (P = <0.01).

One case (1.6%) in misoprostol group, but none in dinoprostone had tachystole (P = 1.00). Abnormal heart rate pattern was found more in misoprostol than dinoprostone 16.6% versus 4.9% (P = 0.14) and so was the incidence of cesarean section, 26.6 versus 15%, respectively (P = 0.47). Meconium passage was the same in both groups, 10% in each group.

Conclusion:  Vaginal misoprostol 50 µg 6‐hourly is safe and effective for induction of labor with lesser need of oxytocin augmentation and shorter induction delivery interval.
Exercise‐induced changes in protein metabolism
Authors: TIPTON K.D. , WOLFE R.R.
Published: May 2003

Exercise has a profound acute effect on protein metabolism. Whereas reports on whole body responses to exercise have varied results, it is generally agreed leucine oxidation is increased during exercise, thus indicating increased net protein breakdown. Following endurance exercise, whole body protein breakdown is generally reduced from resting levels, while following eccentric exercise, both whole body protein breakdown and leucine oxidation are increased. Whole body protein synthesis, on the other hand, is either increased or unchanged. Much of the disagreement in the results of studies on the response of whole body protein metabolism to exercise may be attributed to the limitations of the available methods. Even if the methodology accurately reflects whole body metabolism, this may not reflect changes in the protein metabolism of muscle. Although endurance exercise has not been studied, muscle protein breakdown is increased following resistance exercise. There is a concomitant, and qualitatively greater, increase in muscle protein synthesis following resistance exercise, which may last for as long as 48 h. Increased muscle protein synthesis is linked to increased intramuscular availability of amino acids, and thus, to increased blood flow and increased amino acid delivery to the muscle, as well as increased amino acid transport. Administration of exogenous amino acids after exercise increases protein synthesis while ameliorating protein breakdown, thus improving net muscle protein balance. While it is clear that muscle protein synthesis and protein breakdown increase in a qualitatively similar manner following exercise, the mechanisms of stimulation have yet to be determined. However, we propose that the intracellular availability of amino acids is the link between these processes.
Regulation of GLUT4 protein and glycogen synthase during muscle glycogen synthesis after exercise
Authors: IVY J. L. , KUO C. ‐H.
Published: May 2003

The pattern of muscle glycogen synthesis following its depletion by exercise is biphasic. Initially, there is a rapid, insulin independent increase in the muscle glycogen stores. This is then followed by a slower insulin dependent rate of synthesis. Contributing to the rapid phase of glycogen synthesis is an increase in muscle cell membrane permeability to glucose, which serves to increase the intracellular concentration of glucose‐6‐phosphate (G6P) and activate glycogen synthase. Stimulation of glucose transport by muscle contraction as well as insulin is largely mediated by translocation of the glucose transporter isoform GLUT4 from intracellular sites to the plasma membrane. Thus, the increase in membrane permeability to glucose following exercise most likely reflects an increase in GLUT4 protein associated with the plasma membrane. This insulin‐like effect on muscle glucose transport induced by muscle contraction, however, reverses rapidly after exercise is stopped. As this direct effect on transport is lost, it is replaced by a marked increase in the sensitivity of muscle glucose transport and glycogen synthesis to insulin. Thus, the second phase of glycogen synthesis appears to be related to an increased muscle insulin sensitivity. Although the cellular modifications responsible for the increase in insulin sensitivity are unknown, it apparently helps maintain an increased number of GLUT4 transporters associated with the plasma membrane once the contraction‐stimulated effect on translocation has reversed. It is also possible that an increase in GLUT4 protein expression plays a role during the insulin dependent phase.
Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance
Authors: REID M. B.
Published: May 2003

Over the last two decades, nitric oxide (NO) has been established as a novel mediator of biological processes, ranging from vascular control to long‐term memory, from tissue inflammation to penile erection. This paper reviews recent research which shows that NO and its derivatives also are synthesized within skeletal muscle and that NO derivatives influence various aspects of muscle function. Individual muscle fibres express one or both of the constitutive NO synthase (NOS) isoforms. Type I (neuronal) NOS is localized to the sarcolemma of fast fibres; type III (endothelial) NOS is associated with mitochondria. Isolated skeletal muscle produces NO at low rates under resting conditions and at higher rates during repetitive contraction. NO appears to mediate cell–cell interactions in muscle, including vasodilation and inhibition of leucocyte adhesion. NO also acts directly on muscle fibres to alter cell function. Muscle metabolism appears to be NO‐sensitive at several sites, including glucose uptake, glycolysis, mitochondrial oxygen consumption and creatine kinase activity. NO also modulates muscle contraction, inhibiting force output by altering excitation–contraction coupling. The mechanisms of NO action are likely to include direct effects on redox‐sensitive regulatory proteins, interaction with endogenous reactive oxygen species, and activation of second messengers such as cyclic guanosine monophosphate (cGMP). In conclusion, research published over the past few years makes it clear that skeletal muscle produces NO and that endogenous NO modulates muscle function. Much remains to be learned, however, about the physiological importance of NO actions and about their underlying mechanisms.
Molecular and cellular adaptation of muscle in response to physical training
Authors: BOOTH F. W. , TSENG B. S , FLÜCK M. , CARSON J. A.
Published: May 2003

Molecular biology tools can be used to answer questions as to how adaptations occur in skeletal muscle with training that could provide new frameworks to improve physical performance. A number of mRNAs for transfer of metabolic substrates into muscle cells increase after a single bout of exercise demonstrating the responsiveness of some gene expression to exercise. In stretch‐induced hypertrophy SRE1 of the skeletal α‐actin promoter is required to transactivate the promoter. Less retardation of SRF in crude nuclear extracts from the stretched muscle implies a conformational change in SRF because of the stretch. Transgenic animals will provide a tool to test questions concerned with how exercise signals adaptive changes in gene expression. Molecular biological approaches will be able to evaluate the interaction between physical activity levels and the expression of genes that modulate the susceptibility to many chronic diseases. Benefits of exercise extend beyond fitness to better health. Molecular biology is an important tool which should lead to improved physical performance and health in both elite athletes and the general public.
Skeletal muscle fatigue in normal subjects and heart failure patients. Is there a common mechanism?
Authors: LUNDE P. K. , VERBURG E. , VØLLESTAD N. K. , SEJERSTED O. M.
Published: May 2003

Skeletal muscle fatigue develops gradually during all forms of exercise, and develops more rapidly in heart failure patients. The fatigue mechanism is still not known, but is most likely localized to the muscle cells themselves. During high intensity exercise the perturbations of the Na+and K+balance in the exercising muscle favour depolarization, smaller action potentials and inexcitability. The Na+, K+pump becomes strongly activated and limits, but does not prevent the rise in extracellular Na+, K+pump concentration and intracellular Na+concentration. However, by virtue of its electrogenic property the pump may contribute in maintaining excitability and contractility by keeping the cells more polarized than the ion gradients predict. With prolonged exercise perturbations of Na+and K+are smaller and fatigue may be associated with altered cellular handling of Ca2+and Mg2+. Release of Ca2+from the sarcoplasmic reticulum (SR) is reduced in the absence of changes of the cellular content of Ca2+and Mg2+. In heart failure several clinical reports indicate severe electrolyte perturbations in skeletal muscle. However, in well controlled studies small or insignificant changes are found. We conclude that with high intensity exercise perturbations of Na+and K+in muscle cells may contribute to fatigue, whereas with endurance type of exercise and in heart failure patients the skeletal muscle fatigue is more likely to reside in the intracellular control of Ca2+release and reuptake.
Do immunoassays differentially detect different acidity glycoforms of FSH?
Authors: Oliver Robert L. , Kane John W. , Waite Annelise , Mulders John W. M. , Robertson William R.
Published: May 2003

OBJECTIVE

The possibility of the carbohydrate residues of glycoproteins affecting their recognition in immunoassays is an important and unresolved issue. This study looked for evidence of differential recognition of FSH glycoform preparations, of variable isoelectric point (pI) and known molarity, using three routine assays employing different antibody configurations.

DESIGN

Seven glycoform preparations with differing pI bands (between 3.8 and 5.5) were produced by isoelectric focusing of recombinant human FSH and the molecular weights determined by mass spectroscopy. Three concentrations of each glycoform were assayed and the results expressed relative to unfractionated material. From the relative responses, recognition differences between the assay methods and between the glycoform preparations were investigated.

MEASUREMENTS

Three routine assays were employed: the commercially available Amerlite® enzyme immunoassay and Delfia® immunofluorometric assay, together with an in‐house competitive two‐site radioimmunoassay (RIA).

RESULTS

Overall, the three assays gave the same relative responses for equivalent glycoforms, with the only exceptions involving small differences between some assay pairs for the fractions at the extremes of the pI range investigated. Within each assay type, differences (P < 0.05) of up to 33% existed between glycoforms of different pI, however, these differences showed no patterns or trends across the entire acidity range examined.

CONCLUSIONS

Between the assay methods investigated in this study, few differences exist in the recognition of individual pI bands of FSH when expressed relative to a common unfractionated standard. Differences were apparent in the recognition of the different acidity glycoforms within each assay method, however, these were small and unlikely to be of clinical significance.
Clinical features of women with resistance to luteinizing hormone
Authors: Arnhold Ivo J.P. , Latronico Ana C. , Batista Marcelo C. , Izzo Carlos R. , Mendonca Berenice B.
Published: May 2003

OBJECTIVE

To review clinical and hormonal characteristics of new and published females with LH resistance.

PATIENTS

Seven sisters of patients with male pseudohermaphroditism due to LH resistance.

MEASUREMENTS

Clinical characteristics, hormonal levels, pelvic ultrasound and molecular studies.

RESULTS

Patients had: (1) normal female external genitalia; (2) spontaneous breast and pubic hair development at ages 9–13 years; (3) menarche at 12–20 years, followed by irregular menstrual cycles (3 weeks to 15 months); (4) infertility; (5) withdrawal bleeding after progesterone administration; (6) elevated serum LH levels (10–38 IU/l, normal 0.9–8.4) and elevated LH/FSH ratio with normal androgen levels; (7) low or normal oestradiol levels for the follicular phase; and (8) normal or small uterus and normal or increased ovary size with one or more cysts at ultrasound examination. Ovarian biopsy showed antral follicles and confirmed lack of ovulation. One homozygous mutation in exon 11 of the LH receptor gene was found in each of 4 patients: 1 nonsense (Arg554Stop) and 2 missense mutations (Glu354Lys and Ala593Pro) and 1 microdeletion (Leu‐608, Val‐609) were found. In 3 patients (1 family) with the same phenotypic characteristics, no mutations in the coding sequence of the LH receptor gene were found.

CONCLUSIONS

We conclude that women with LH resistance have spontaneous breast development, primary or secondary amenorrhoea, infertility, elevated serum LH levels and LH/FSH ratio with normal androgen levels and normal or enlarged cystic ovaries. Therefore, in females, primary and secondary sexual characteristics develop independently of LH action. However, LH stimulation is necessary for normal ovarian steroidogenesis and ovulation.
The dexamethasone‐suppressed corticotrophin‐releasing hormone stimulation test in anorexia nervosa
Authors: Duclos M. , Corcuff J‐B. , Roger P. , Tabarin A.
Published: May 2003

OBJECTIVE

The dexamethasone–CRH test (combination of dexamethasone‐induced suppression of HPA axis function and subsequent stimulation with oCRH) (Dex–CRH test) has been proposed to fully distinguish ACTH‐dependent Cushing's disease (CD) from pseudo‐Cushing's states (PCS), i.e. tumoural vs. functional hypercortisolism. A plasma cortisol concentration greater than 38 nmol/l 15 min after CRH injection has been demonstrated to identify all cases of CD and to exclude all cases of PCS. Although obviously not a PCS from a clinical point of view, anorexia nervosa (AN) is associated with CRH‐driven hyperactivity of the HPA axis. This study reports the response of AN patients, a model of functional biological hypercortisolism, to the Dex–CRH test.

PATIENTS AND METHODS

Nineteen women affected with anorexia nervosa and 6 healthy sex‐matched controls were studied.

RESULTS

Three of 19 AN patients had an abnormal 24‐h urinary free cortisol excretion (UFC), whereas 1 of 19 AN had increased overnight UFC. AN subjects had inadequately suppressed plasma cortisol after low‐dose dexamethasone suppression test (LDDST) (cortisol 192.8 ± 63.4 vs. < 27 nmol/l, AN vs. controls, respectively). Seven of 19 AN patients had plasma cortisol levels above 50 nmol/l after LDDST. None of the AN patients had CRH‐induced increases in plasma ACTH or cortisol (basal cortisol 192.8 ± 63.4 and peak cortisol 181.7 ± 59.9 nmol/l). Despite unresponsivenessto CRH and because of the lack of suppression after dexamethasone, using the single plasma cortisol threshold value of 38 nmol/l obtained at 15 min during the Dex–CRH test would have been misclassified in half of our AN population (9 of 19).

CONCLUSION

Since anorexia nervosa represents a model of functional hypercortisolism that shares similar pathophysiological mechanisms to the other causes of pseudo‐Cushing's states, we suggest testing all causes of pseudo‐Cushing's states using the dexamethasone–CRH approach to (i) describe the actual responses of clinically relevant pseudo‐Cushing's states and (ii) to improve our knowledge of the pathophysiological discrepancies between the various causes of pseudo‐Cushing's states. Lastly, the evaluation of dexamethasone metabolism (absorption, volume of distribution, clearance) may help to gain more insight into the diagnostic value of the dexamethasone–CRH test.
Birth weight affects final height in patients treated for growth hormone deficiency
Authors: Cacciari E. , Zucchini S. , Cicognani A. , Pirazzoli P. , Balsamo A. , Salardi S. , Cassio A. , Pasini A. , Gualandi S.
Published: May 2003

OBJECTIVE

Birth weight influences both postnatal growth and the initial response to GH therapy in GH‐deficient subjects, but its relationship to final height is uncertain. Therefore, we examined final height results in a group of subjects treated for GH deficiency who were born small, appropriate or large for gestational age (GA).

DESIGN

Retrospective study.

PATIENTS

108 GH‐treated patients (age at diagnosis 11.1 ± 2.0 years) affected by idiopathic and isolated GH deficiency (peak < 8 μg/l after pharmacological and/or nocturnal mean GH concentration ≤ 3.3 μg/l) were examined. Twenty‐four had a birth weight < 3rd centile (2300 g ± 268 − small for GA), 77 between the 3rd and 90th centile (3216 g ± 317: appropriate for GA) and 7 above the 90th centile (4193 g ± 143: large for GA).

MEASUREMENTS

All subjects reached final height (growth velocity < 0.5 cm/year in the last year of treatment) after hGH treatment (range 33–96 months) at a dose of 20 U/m2/week. The 3 groups of subjects started therapy at a similar height for chronological and bone age.

RESULTS

Final height in the small for GA group was − 1.71 ± 0.93 standard deviation score (SDS), significantly lower than that of both appropriate (− 1.14 ± 0.83 (P < 0.01)) and large (− 0.70 ± 0.89 (P < 0.01)) for GA groups. Similarly, the small for GA group had a significantly lower height SDS increment from the start of therapy to adult height (0.54 ± 0.84) than both the appropriate (0.99 ± 0.78 (P < 0.05)) and the large (1.49 ± 0.84 (P < 0.01)) for GA groups. The percentage of subjects with final height above target height was significantly different in the 3 groups: 21% for the small, 38% for the appropriate and 71% for the large for GA groups (P < 0.05). In the whole group of patients there was a positive correlation between birth weight and final height (r = 0.38; P < 0.0001).

CONCLUSIONS

The present study showed that our patients, affected by isolated and idiopathic GH deficiency but with different birth weights, despite starting treatment with a similar height and bone age delay, had different auxological outcomes. It seems, therefore, that final height is strongly influenced by birth weight which penalizes the smaller newborns and assists the larger ones.
Association of CTLA‐4 polymorphism with positive anti‐GAD antibody in Japanese subjects with type 1 diabetes mellitus
Authors: Hayashi Hiroko , Kusaka Ikuyo , Nagasaka Shoichiro , Kawakami Akio , Rokkaku Kumiko , Nakamura Tomoatsu , Saito Takako , Higashiyama Minori , Honda Kazufumi , Ishikawa San‐e , Saito Toshikazu
Published: May 2003

OBJECTIVE

CTLA‐4, expressed on activated T cells, is thought to be a negative regulator of T cell function. Its gene (2q33) may confer genetic susceptibility to type 1 diabetes mellitus (IDDM12). The present study was undertaken to clarify the role of CTLA‐4 gene polymorphism in Japanese subjects with type 1 diabetes and its effect on their clinical features.

SUBJECTS AND METHODS

In 117 Japanese subjects with type 1 diabetes, the CTLA‐4 exon 1 polymorphism (49 A/G) was defined by PCR‐RFLP analysis. Anti‐GAD antibodies (GAD‐Ab) and fasting serum C‐peptide were also determined. 141 healthy age‐ and sex‐matched subjects served as controls.

RESULTS

The frequency of each polymorphism was not different between the type 1 diabetic subjects and the controls; AA 21, AG 42 and GG 54 for the diabetic subjects, and AA 22, AG 47 and GG 72 for the controls. The frequency of the GG genotype was higher in the diabetic subjects with positive GAD‐Ab (greater than 8 U/ml) (67%) than in the GAD‐Ab negative subjects (39%) (P < 0.05). The prevalence of positive GAD‐Ab declined with the duration of diabetes. In the diabetic subjects with disease duration of less than 5 years (n = 40), the frequency of the GG genotype was also higher in the GAD‐Ab positive subjects (71%) (P < 0.05). In the analysis of all the diabetic subjects, there was a strong association between positive GAD‐Ab and β cell function (P < 0.0001).

CONCLUSIONS

There was no evidence that the CTLA‐4 exon 1 polymorphism (49 A/G) confers genetic susceptibility to type 1 diabetes mellitus in our case‐control study in Japanese subjects. However, the frequency of positive GAD‐Ab was higher in the GG subjects. CTLA‐4 polymorphism might contribute to the clinical heterogeneity of type 1 diabetes mellitus in Japanese subjects.
Autologous Blood Procurementin the Surgical Setting:Lessons Learned in the Last 10 years
Authors: Goodnough Lawrence Tim , Monk Terri G. , Brecher Mark E.
Published: May 2003

The percentage of blood transfused yearly that is autologous has increased substantially over the last 10 years. While autologous blood is regarded as a standard of care in many elective surgical settings, the increasing safety of allogeneic blood and the expense of autologous blood procurement have raised questions regarding the appropriate roles of autologous blood in blood conservation strategies. We therefore review current activities and emerging questions that arise from this maturing arena.