bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic regulation of Na+-K+-2Cl− cotransporter surface expression by PKC-ε in Cl−-secretory epithelia
Authors: Del Castillo Isabel Calvo , Fedor-Chaiken Mary , Song J. Cecilia , Starlinger Veronika , Yoo James , Matlin Karl S. , Matthews Jeffrey B.
Published: July 2005

In secretory epithelia, activation of PKC by phorbol ester and carbachol negatively regulates Cl− secretion, the transport event of secretory diarrhea. Previous studies have implicated the basolateral Na+-K+-2Cl− cotransporter (NKCC1) as a target of PKC-dependent inhibition of Cl− secretion. In the present study, we examined the regulation of surface expression of NKCC1 in response to the activation of PKC. Treatment of confluent T84 intestinal epithelial cells with the phorbol ester 12- O-tetradecanoylphorbol-13-acetate (PMA) reduced the amount of NKCC1 accessible to basolateral surface biotinylation. Loss of cell surface NKCC1 was due to internalization as shown by 1) the resistance of biotinylated NKCC1 to surface biotin stripping after incubation with PMA and 2) indirect immunofluorescent labeling. PMA-induced internalization of NKCC1 is dependent on the ε-isoform of PKC as determined on the basis of sensitivity to a panel of PKC inhibitors. The effect of PMA on surface expression of NKCC1 was specific because PMA did not significantly alter the amount of Na+-K+-ATPase or E-cadherin available for surface biotinylation. After extended PMA exposure (>2 h), NKCC1 became degraded in a proteasome-dependent fashion. Like PMA, carbachol reduced the amount of NKCC1 accessible to basolateral surface biotinylation in a PKC-ε-dependent manner. However, long-term exposure to carbachol did not result in degradation of NKCC1; rather, NKCC1 that was internalized after exposure to carbachol was recycled back to the cell membrane. PKC-ε-dependent alteration of NKCC1 surface expression represents a novel mechanism for regulating Cl− secretion.
Modulation of Membrane Potential in Mesothoracic Moto- and Interneurons During Stick Insect Front-Leg Walking
Authors: Ludwar Björn Ch. , Westmark Sandra , Büschges Ansgar , Schmidt Joachim
Published: July 2005

During walking, maintenance and coordination of activity in leg motoneurons requires intersegmental signal transfer. In a semi-intact preparation of the stick insect, we studied membrane potential modulations in mesothoracic (middle leg) motoneurons and local premotor nonspiking interneurons that were induced by stepping of a front leg on a treadmill. The activity in motoneurons ipsi- and contralateral to the stepping front leg was recorded from neuropilar processes. Motoneurons usually exhibited a tonic depolarization of ≤5 mV throughout stepping sequences. This tonic depolarization depended on membrane potential and was found to reverse in the range of −32 to −47 mV. It was accompanied by a mean membrane resistance decrease of ∼12%. During front-leg stepping, an increased spike activity to depolarizing current pulses was observed in 73% of contralateral flexor motoneurons that were tested. Motoneurons ipsilateral to the walking front leg exhibited phasic membrane potential modulations coupled to steps in accordance with previously published results. Coupling patterns were typical for a given motoneuron pool. Local nonspiking mesothoracic interneurons that provide synaptic drive to tibial motoneurons also contribute to the modulation of membrane potential of tibial motoneurons during front-leg walking. We hypothesize that the tonic depolarization of motoneurons during walking is a cellular correlate of arousal that usually increases effectiveness of phasic excitation in supporting motoneuron firing.
Wisdom, Theodicy, Death, and the Evolution of Intellectual Traditions
Authors: Sanders Jack
Published: July 2005

When one reads through the main Judaic wisdom texts chronologically, one sees the rise of the problem of theodicy and the resultant attempt to solve the problem. All the sages after the authors of Proverbs treat this problem in one way or another, and one can follow a course from the awareness of the problem in Job to its complete solution in the book of Wisdom and in 4QInstruction, where versions of a belief in an existence beyond death finally make their way into the tradition. Even this adaptation, however, did not ensure the survival of the wisdom tradition.
Score-Celebration Injuries among Soccer Players
Authors: Zeren Bülent , Öztekin Haluk H.
Published: July 2005

Background

Professional and amateur soccer players often perform dramatic on-field feats of celebration after scoring a goal. Injuries may occur during these activities.

Purpose

With the aim of preventing such “score-celebration injuries” in the future, the authors examine these events in professional soccer players and discuss potential avenues for prevention.

Study Design

Case series; Level of evidence, 4.

Methods

Over the course of 2 seasons (1996-1998), 152 soccer players were evaluated at an orthopaedic clinic for injuries incurred during matches. Nine players (6%) had injured themselves while celebrating after scoring goals in a match. The type of celebration, injury type, treatment, and mean duration of recovery were noted.

Results

Seven of the 9 patients were male professional soccer players with ages ranging between 17 and 29 years (mean age, 24 years). The injuries occurred when the playing ground was natural turf in 8 cases; most injuries occurred in the second half of the game. The types of celebration maneuvers were sliding (prone or supine) and sliding while kneeling in 5 cases, piling up on jubilant teammates in 3 cases, and being tackled while racing away in 1 case. Injuries included ankle, clavicle, and rib fractures; medial collateral ligament sprain; low back strain; hamstring and adductor muscle strain; quadriceps muscle sprain; and coccyx contusion. The mean duration for recovery was 6.2 weeks. Rival team players were usually not responsible for such trauma.

Conclusion

Exaggerated celebrations after making a goal, such as sliding, piling up, and tackling a teammate when racing away, can result in serious injury. In addition to general measures for preventing soccer injuries, coaches and team physicians should teach self-control and behavior modification to minimize the risk of such injuries. More restrictive rules, which penalize such behavior, may assist in the prevention of score-celebration injuries.
Assessment of an electronic voting system within the tutorial setting: A randomised controlled trial [ISRCTN54535861]
Authors: Palmer Edward J , Devitt Peter G , De Young Neville J , Morris David
Published: July 2005

Background

Electronic voting systems have been used in various educational settings with little measurement of the educational impact on students. The goal of this study was to measure the effects of the inclusion of an electronic voting system within a small group tutorial.

Method

A prospective randomised controlled trial was run at the Royal Adelaide Hospital, a teaching hospital in Adelaide, Australia. 102 students in their first clinical year of medical school participated in the study where an electronic voting system was introduced as a teaching aid into a standard tutorial. Long-term retention of knowledge and understanding of the topics discussed in the tutorials was measured and student response to the introduction of the electronic voting system was assessed.

Results

Students using the electronic voting system had improved long-term retention of understanding of material taught in the tutorial. Students had a positive response to the use of this teaching aid.

Conclusion

Electronic voting systems can provide a stimulating learning environment for students and in a small group tutorial may improve educational outcomes.
Effect of antithrombin III on neutrophil deformability
Authors: Saito Hajime , Minamiya Yoshihiro , Kalina Uwe , Saito Satoshi , Ogawa Jun-ichi
Published: July 2005

As the spherical diameter of pulmonary capillaries is smaller than that of neutrophils, increased neutrophil stiffness or conversely, decreased neutrophil deformability is a key step in the initial sequestration of neutrophils within the lungs during inflammatory processes. Antithrombin III (AT) is known to exert a therapeutic effect against disseminated intravascular coagulation, and accumulating evidence suggests that AT also has anti-inlammatory properties. The mechanisms of its anti-inflammatory effects remain unclear, but in a rat endotoxin model, AT apparently inhibited neutrophil sequestration in the lung. In the present in vitro study, therefore, we examined the effect of AT on the deformability of human neutrophils and correlated those findings with their F-actin content. Isolated human neutrophils were stimulated with formyl-Met-Leu-Phe (1 μM, 2 min) in the presence or absence of the α, β, or low heparin-affinity isoforms of AT (1 IU/ml, 20 min), and deformability was evaluated using a filter assay system. Neutrophils were also stained with fluorescein isothiocyanate-phalloidin and subjected to a fluorescein-activated cell sorter scan to assess F-actin content. The results showed that pretreatment with any of the three AT isoforms similarly inhibited the decreased neutrophil deformability and increased F-actin content of stimulated cells. Notably, heparinase had no effect on deformability or F-actin content in the presence or absence of AT, which was somewhat unexpected, as heparin sulfate proteoglycans likely function as AT receptors. These findings suggested that AT inhibits the increase in neutrophil stiffness seen during inflammatory processes by inhibiting actin polymerization via a heparin-independent pathway.
Negative regulatory role of mannose receptors on human alveolar macrophage proinflammatory cytokine release in vitro
Authors: Zhang Jianmin , Tachado Souvenir D , Patel Naimish , Zhu Jinping , Imrich Amy , Manfruelli Pascal , Cushion Melanie , Kinane T Bernard , Koziel Henry
Published: July 2005

Alveolar macrophages (AM) are critical components of lung innate immunity and contribute to an effective host response to Pneumocystis pneumonia. Recognition of unopsonized Pneumocystis organisms by human AM is mediated predominantly via mannose receptors and results in phagocytosis, release of reactive oxygen species, and activation of the nuclear transcription factor (NF)-κB. However, the AM host defense genes activated by Pneumocystis have not been defined. In the present study, incubation of AM with unopsonized Pneumocystis organisms was not associated with release of interleukin (IL)-1β, IL-6, or tumor necrosis factor (TNF)-α (important cytokines in the host response to Pneumocystis) and did not induce IL-1β, IL-6, or TNF-α mRNA transcripts. These findings were not attributed to Pneumocystis-induced cytopathic changes, as these same AM released IL-8 and matrix metalloproteinase-9 in response to Pneumocystis. NF-κB-mediated IL-8 release was independent of Pneumocystis phagocytosis. The observed response was specific, as IL-1β, IL-6, and TNF-α release and mRNA induction were preserved in response to lipopolysaccharide or serum-opsonized Pneumocystis. The absence of IL-1β, IL-6, and TNF-α release in response to Pneumocystis was predominately influenced by AM mannose receptors, as blocking mannose receptors or targeted mannose receptor small interfering RNA functional gene silencing resulted in TNF-α release in response to unopsonized Pneumocystis organisms. Furthermore, ligation of AM mannose receptors by unopsonized Pneumocystis organisms reduced Toll-like receptor 4-mediated TNF-α release. Taken together, these data suggest that mannose receptors on human AM may suppress select proinflammatory cytokine release and may serve to regulate the innate inflammatory responses to infectious challenge in the lungs.
Latent Learning and Deferred Imitation at 3 Months
Authors: Campanella Jennifer , Rovee‐Collier Carolyn
Published: July 2005

Young infants spend most of their waking time looking around, but whether they learn anything about what they see is unknown. We used a sensory preconditioning paradigm and a deferred imitation task to assess if 3‐month‐olds formed a latent association between 2 objects (S1, S2) that they merely saw together. Because infants cannot perform the imitation task until 6 months, we maintained the latent memory with periodic reminders until then, when we modeled the target actions on S1 and tested them with S2 24 hr later. At 6 months of age, infants who had seen S1 and S2 paired (but not unpaired) deferred imitation on S2, confirming that they had associated the objects 3 months earlier. In addition, 3‐month‐olds who saw the objects paired and then saw the target actions modeled on S1 for 60 sec also recalled and imitated them on S2 3 months later, at 6 months of age. These data reveal that latent learning by very young infants is both extensive and enduring and document that the knowledge base begins to form early in life, long before infants are able to express what they know.
Avoidance of Heights on the Visual Cliff in Newly Walking Infants
Authors: Witherington David C. , Campos Joseph J. , Anderson David I. , Lejeune Laure , Seah Eileen
Published: July 2005

Work with infants on the “visual cliff” links avoidance of drop‐offs to experience with self‐produced locomotion. Adolph's (2002) research on infants' perception of slope and gap traversability suggests that learning to avoid falling down is highly specific to the postural context in which it occurs. Infants, for example, who have learned to avoid crossing risky slopes while crawling must learn anew such avoidance when they start walking. Do newly walking infants avoid crossing the drop‐off of the visual cliff? Twenty prewalking but experienced crawling infants were compared with 20 similarly aged newly walking infants on their reactions to the visual cliff. Newly walking infants avoided moving onto the cliff's deep side even more consistently than did the prewalking crawlers. Thus, in the context of drop‐offs in visual texture, our results show that once avoidance of drop‐offs is established under conditions of crawling, it is developmentally maintained once infants begin walking.
Expressive Vocabulary in Language Learners From Two Ecological Settings in Three Language Communities
Authors: Bornstein Marc H. , Cote Linda R.
Published: July 2005

This study compared multiple characteristics of girls' and boys' vocabulary in 6 different linguistic communities—1 urban and 1 rural setting in each of 3 countries. Two hundred fifty‐two mothers in Argentina, Italy, and the United States completed vocabulary checklists for their 20‐month‐old children. Individual variability was substantial within each linguistic community. Minimal cross‐linguistic differences were found in children's vocabulary size; however, differences among languages in the composition of children's vocabularies appeared possibly related to cultural valuing of different categories of words. Ecological setting differences within cultures appeared in children's vocabulary size, even when the composition of children's vocabularies was examined: Children living in urban areas were reported by their mothers to say significantly more words than children living in rural areas, particularly for Argentine and U.S. children. Girls had consistently larger vocabularies than boys. These findings are discussed in terms of contextual and child factors that together influence first language learning.
Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome
Authors: Palomba Stefano , Orio Francesco , Falbo Angela , Manguso Francesco , Russo Tiziana , Cascella Teresa , Tolino Achille , Carmina Enrico , Colao Annamaria , Zullo Fulvio
Published: July 2005

Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients.

Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS.

Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial.

Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy.

Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated.

Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each.

Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates.

Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).

Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.
Oxytocin Inhibits T-Type Calcium Current of Human Decidual Stromal Cells
Authors: Liu Bo , Hill Stephen J. , Khan Raheela N.
Published: July 2005

Context: Little is known about the crosstalk between the decidua and myometrium in relation to human labor. The hormone oxytocin (OT) is considered to be a key mediator of uterine contractility during parturition, exerting some of its effects through calcium channels.

Objective: The objective was to characterize the effect of OT on the T-type calcium channel in human decidual stromal cells before and after the onset of labor.

Design: The nystatin-perforated patch-clamp technique was used to record inward T-type calcium current (ICa(T)) from acutely dispersed decidual stromal cells obtained from women at either elective cesarean section [CS (nonlabor)] or after normal spontaneous vaginal delivery [SVD (labor)].

Setting: These studies took place at the University of Nottingham Medical School.

Results: I Ca(T) of both SVD and CS cells were blocked by nickel (IC50 of 5.6 μm) and cobalt chloride (1 mm) but unaffected by nifedipine (10 μm). OT (1 nm to 3.5 μm) inhibited ICa(T) of SVD cells in a concentration-dependent manner, with a maximal inhibition of 79.0% compared with 26.2% in decidual cells of the CS group. OT-evoked reduction of ICa(T) was prevented by preincubation with the OT antagonist L371,257 in the SVD but not CS group. OT, in a concentration-dependent manner, displaced the steady-state inactivation curve for ICa(T) to the left in the SVD group with no significant effect on curves of the CS group.

Conclusion: Inhibition of ICa(T) by OT in decidual cells obtained during labor may signify important functional remodeling of uterine signaling during this period.
C-terminal mutants ofC. elegansSmads reveal tissue-specific requirements for protein activation by TGF-β signaling
Authors: Wang Jianjun , Mohler William A. , Savage-Dunn Cathy
Published: July 2005

TGF-β signaling in the nematode Caenorhabditis elegans plays multiple roles in the development of the animal. The Sma/Mab pathway controls body size, male tail sensory ray identity and spicule formation. Three Smad genes, sma-2, sma-3 and sma-4, are all required for signal transduction, suggesting that the functional complex could be a heterotrimer. Because the C termini of Smads play important roles in receptor-mediated activation and heteromeric complex formation, we generated C-terminal mutations in the C. elegans Smad genes and tested their activities in vivo in each of their distinct developmental roles. We show that pseudophosphorylated SMA-3 is dominant negative in body size, but functional in sensory ray and spicule development. Somewhat differently,pseudophosphorylated SMA-2 is active in any tissue. The C-terminal mutants of SMA-4 function like wild type, suggesting that the SMA-4 C terminus is dispensable. Using a combination of different C-terminal mutations in SMA-2 and SMA-3, we found a complex set of requirements for Smad-phosphorylation state that are specific to each outcome. Finally, we detected a physical interaction of SMA-3 with the forkhead transcription factor LIN-31, which is enhanced by SMA-3 pseudophosphorylation and reduced in an unphosphorylatable mutant. We conclude that the tissue-specific requirements for Smad phosphorylation may result, in part, from the need to interact with tissue-specific transcription co-factors that have different affinities for phosphorylated and unphosphorylated Smad protein.
Immediate and Sustained Changes in Tongue Movement with an Experimental Palatal “Fistula”: A Case Study
Authors: Marino Viviane C. C. , Williams William N. , Wharton Paul W. , Paulk Martha F. , Dutka-Souza Jeniffer C. R. , Schulz Geralyn M.
Published: July 2005

Objective

To determine the immediate and longer-term effect(s) on tongue movement following the placement of an experimental opening through a palatal obturator (replicate of subject's prosthesis) worn by an adult male with an unrepaired cleft of the hard and soft palate.

Methods

Tongue movements associated with an anterior experimental opening of 20 mm2 were examined under three conditions: a control condition in which the subject wore the experimental obturator completely occluded, a condition immediately after drilling the experimental openings through the obturator, and a condition after 5 days in which the subject wore the experimental obturator with the experimental opening. An Electromagnetic Articulograph was used for obtaining tongue movements during speech.

Results

The findings partly revealed that the immediate introduction of a perturbation to the speech system (experimental fistula) had a temporary effect on tongue movement. After sustained perturbation (for 5 days), the system normalized (going back toward control condition's behavior). Perceptual data were consistent with kinematic tongue movement direction in most of the cases.

Conclusions

Although the immediate response can be interpreted as indicative of the subject's attempts to move the tongue toward the opening to compensate for air loss, the findings following a sustained perturbation indicate that with time, other physiological adjustments (such as respiratory adjustments, for example) may help reestablish the requirements of a pressure-regulating system.
Evaluation of Esthetic, Functional, and Quality-of-Life Outcome in Adult Cleft Lip and Palate Patients
Authors: Sinko Klaus , Jagsch Reinhold , Prechtl Verena , Watzinger Franz , Hollmann Karl , Baumann Arnulf
Published: July 2005

Objective

Evaluation of esthetic, functional, and health-related quality-of-life (HRQoL) outcomes in adult patients with a repaired cleft lip and palate. The treatment for all patients was based on the so-called Vienna concept.

Patients/Design

Seventy adult patients with a repaired complete cleft lip and palate, ranging in age from 18 to 30 years, were included in the study. Esthetic and functional outcomes were assessed by the patients themselves and by five experts using a visual analog scale. Patients also completed the MOS Short-Form 36 questionnaire to evaluate health-related quality of life.

Results

Patients rated their esthetic outcome significantly worse than the experts did. No significant differences were observed in the ratings for function. Female patients, especially, were dissatisfied with their esthetic outcomes. In a personal interview, nearly 63% of them asked for further treatment, particularly for upper-lip and nose corrections. The health-related quality-of-life questionnaire revealed low scores for only two subscales, namely social functioning and emotional role. In most subscales of health-related quality of life, patients who desired further treatment had significantly lower scores than did patients who desired no further treatment.

Conclusion

Surgery of the lip and nose appears to be of prime importance for patients with a cleft lip and palate. Cleft patients who do not request secondary treatment are not always satisfied with the treatment. Patients with realistic expectations in regard to further treatment should be treated by specialists, whereas those with unrealistic expectations should be referred to a clinical psychologist.
A Quantitative Three-Dimensional Assessment of Abnormal Variations in the Facial Soft Tissues of Individuals with down Syndrome
Authors: Sforza Chiarella , Dellavia Claudia , Dolci Claudia , Donetti Elena , Ferrario Virgilio F.
Published: July 2005

Objective

To supply quantitative information about the facial soft tissues of subjects with Down syndrome by using summary anthropometric measurements.

Design, Setting, and Patients

The three-dimensional coordinates of soft tissue facial landmarks were obtained using a computerized digitizer in 28 subjects with Down syndrome (11 girls and women and 17 boys and men aged 12 to 45 years) and 429 healthy controls matched for sex, age, and ethnicity. From the landmarks, 18 facial dimensions were calculated. Data were compared with those collected in healthy individuals by computing z-scores. Two summary anthropometric measurements for quantifying craniofacial variations were assessed in both the subjects with Down syndrome and the reference subjects: the mean z-score (an index of overall facial size) and its standard deviation, craniofacial variability index (an index of facial harmony).

Results

In subjects with Down syndrome, facial size was smaller than in normal individuals, and in 17 subjects the mean z-score fell outside the normal interval (mean ± 2 SD). Twenty subjects had a craniofacial variability index larger than the normal interval.

Conclusions

The facial soft tissue structures of subjects with Down syndrome differed from those of normal controls of the same age, sex, and ethnic group: a reduced facial size was coupled with a global anomalous relationship between individual measurements. The two indices allowed discriminating more than 89% of subjects with Down syndrome when compared with normal subjects.
The new biology of aldosterone
Authors: Connell John M C , Davies Eleanor
Published: July 2005

Classically, aldosterone is synthesised in the adrenal zona glomerulosa and binds to specific mineralocorticoid receptors located in the cytosol of target epithelial cells. Translocation of the resulting steroid receptor complex to the cell nucleus modulates gene expression and translation of specific ‘aldosterone-induced’ proteins that regulate electrolyte and fluid balance. However, non-epithelial and rapid non-genomic actions of aldosterone have also been described that account for a variety of actions of aldosterone that contribute to blood pressure homeostasis. These include key actions on endothelial cells and on cardiac tissue.

There is also evidence that aldosterone can be synthesised in other tissues; the most convincing evidence relates to the central nervous system. However, suggestions that aldosterone is produced in the heart remain controversial, and adrenal derived aldosterone is the principal source of circulating and locally available hormone.

Recent studies have shown major therapeutic benefits of mineralocorticoid receptor antagonism in cardiac failure, which emphasise the importance of aldosterone in causing adverse cardiovascular pathophysiological effects. Additional evidence demonstrates that aldosterone levels predict development of high blood pressure in normotensive subjects, while it is now clear that increased aldosterone action contributes to hypertension and cardiovascular damage in approximately 10% of patients with established hypertension.

These new findings highlight the role of aldosterone as a key cardiovascular hormone and extend our understanding of its role in determining adverse cardiovascular outcomes.
Influence of exogenous oestrogen or (anti-) androgen administration on soluble transferrin receptor in human plasma
Authors: T’Sjoen Guy G , Beguin Yves , Feyen Els , Rubens Robert , Kaufman Jean-Marc , Gooren Louis
Published: July 2005

The objective of this investigation was to study the effects of sex steroids on levels of haemoglobin (Hb) and haematocrit (Hct) and to analyse whether these effects can be related to levels of the soluble transferrin receptor (sTfR), a marker of erythropoietic activity. Nineteen male-to-female transsexuals were randomly assigned to either oral ethinyl oestradiol (EE) (n=12) or transdermal 17β-oestradiol (E2) (n=7); both treatments included the anti-androgen cyproterone acetate (CA). Six male-to-female transsexuals were treated with CA only. Fifteen female-to-male transsexuals were treated with i.m. testosterone esters. The Hct, and levels of Hb, IGF-I, GH and sTfR were measured before and after 4 months of hormone administration. Androgen administration significantly increased the sTfR concentration by 31.5% (P=0.008) and increased levels of Hct, Hb and IGF-I. Both regimens of CA with oral EE and transdermal E2 reduced plasma testosterone similarly to castrate values and decreased Hb and Hct. The CA+oral EE combination induced a decrease in sTfR of 19.0% (P=0.002) which was not the case with CA+transdermal E2 (P=0.27). This cannot be explained by the profound decline in plasma testosterone which was similar with both regimens, but this difference could be related to the different effects of the two regimens on plasma IGF-I. This assumption is supported by the positive correlation that was found to exist between plasma sTfR and IGF-I after the interventions (P<0.05).
Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS-1 cell clone transplantation and the deleterious effects of the drugs are limited: in vivo and in vitro studies
Authors: Asfari M , Berta S , Coffy S , Kergoat M , Charon C , Audet A
Published: July 2005

One of the major requirements for a successful and life-lasting organ transplant is the access to safe, least toxic and permanent tolerance-inducing drugs. In this study we wished to evaluate the effects of tolerogenic doses of the immunosuppressive drugs mycophenolic acid (MPA) and tacrolimus (Tac) on clonal β-cell lines, both in vivo and in vitro. Here we demonstrate that combined administration of low-dose MPA and Tac for 23 days induced permanent tolerance in an allogeneic β-cell line transplant in Wistar rat liver through the portal vein. This short-term treatment of tolerogenic doses of the two drugs was deleterious to the survival of the transplanted cells but a small percentage of the cells could resist the effect and become fully active when the drugs were removed. The surviving cells, retrieved from growth in vivo, did not exhibit increased resistance in comparison to the original cells when tested in vitro at two glucose concentrations, 10 and 20 mM. The presence of a small percentage of resistant cells at the two glucose concentrations was also detected in the in vitro study after a continuous 8-day treatment demonstrating that the in vivo resistance was not related to micro-environmental protection but possibly to a phenotypic cell state that is yet to be determined.
Role of Cdx-2 in insulin and proglucagon gene expression: a study using the RIN-1056A cell line with an inducible gene expression system
Authors: Zhao Yi , Liu Tao , Zhang Nina , Yi Fenghua , Wang Qinghua , Fantus Ivan George , Jin Tianru
Published: July 2005

Although the homeobox gene Cdx-2 was initially isolated from the pancreatic β cell line HIT-T15, no examination of its role in regulating endogenous insulin gene expression has been reported. To explore further the role of Cdx-2 in regulating both insulin and proglucagon gene expression, we established an ecdysone-inducible Cdx-2 expression system. This report describes a study using the rat insulinoma cell line RIN-1056A, which abundantly expresses both insulin and proglucagon (glu), and relatively high amounts of endogenous Cdx-2. Following the introduction of the inducible Cdx-2 expression system into this cell line and the antibiotic selection procedure, we obtained novel cell lines that displayed dramatically reduced expression of endogenous Cdx-2, in the absence of the inducer. These novel cell lines did not express detectable amounts of glu mRNA or the glucagon hormone, while their insulin expression was not substantially affected. In the presence of the inducer, however, transfected Cdx-2 expression was dramatically increased, accompanied by stimulation of endogenous Cdx-2 expression. More importantly, activated Cdx-2 expression was accompanied by elevated insulin mRNA expression, and insulin synthesis. Cdx-2 bound to the insulin gene promoter enhancer elements, and stimulated the expression of a luciferase reporter gene driven by these enhancer elements. Furthermore, Cdx-2 and insulin gene expressions in the wild-type RIN-1056A cells were stimulated by forskolin treatment, and forskolin-mediated activation on insulin gene expression was attenuated in the absence of Cdx-2. We suggest that Cdx-2 may mediate the second messenger cAMP in regulating insulin gene transcription.
A paradoxical inhibitory effect of oestradiol-17β on GnRH self-priming in pituitaries from tamoxifen-treated rats
Authors: Sánchez-Criado José E , Bellido Carmina , Aguilar Rafaela , Garrido-Gracia José C
Published: July 2005

Two-week ovariectomized (OVX) rats were injected over three days with 25 μg oestradiol benzoate (EB), 3 mg tamoxifen (TX) and 0.2 ml oil and their pituitaries were harvested for incubation experiments. Pituitaries from EB-and TX-treated OVX rats exhibited GnRH self-priming when incubated with their corresponding ligand. However, incubation of pituitaries with different ligands yielded divergent results: when pituitaries from EB-treated rats were incubated with 10−7 M TX they displayed GnRH self-priming, whereas incubation of pituitaries from TX-treated rats with 10−8 M oestradiol-17β (E2) blocked GnRH self-priming. Further studies to analyse the latter finding revealed that: (a) E2 inhibited TX-induced GnRH self-priming in a dose-dependent manner while 10−8 M oestradiol-17α did not; (b) co-incubation of E2 with the pure anti-oestrogen ICI 182,780, but not with the selective oestrogen receptor modulator TX, reversed the E2 inhibitory effect; (c) the oestrogen receptor (ER)-α selective agonist propylpyrazole triol, but not the ERβ selective agonist diarylpropionitrile, mimicked the inhibitory effect of E2; (d) the analogue membrane-impermeable conjugated E2-BSA also inhibited TX-induced GnRH self-priming; and (e) a 15-min exposure of the pituitaries to E2 was sufficient to inhibit the GnRH self-priming elicited by TX. Although other explanations may exist, altogether these results suggested that E2, via an ER different from classical ER, inhibits the GnRH self-priming elicited by TX.
Inertial and interfacial effects on pressure drop of Taylor flow in capillaries
Authors: Kreutzer Michiel T. , Kapteijn Freek , Moulijn Jacob A. , Kleijn Chris R. , Heiszwolf Johan J.
Published: July 2005

In a capillary, the two‐phase pressure drop in Taylor slug flow was measured. A carefully designed inlet section for the capillary allowed the independent variation of gas bubble and liquid slug length. Gas and liquid superficial velocities were varied from 0.04 m/s to 0.3 m/s. If the slug length was smaller than 10 times the capillary diameter, the length‐averaged friction factor for the liquid slug increased drastically from the single phase value (f = 16/Re) due to differences in curvature at the front and the back of the bubble. The use of different liquids allowed the independent variation of Re and Ca. The flow of elongated bubbles in capillaries was simulated using the CFD code FIDAP. It was found both numerically and experimentally that for Re ≫ 1, the extra pressure terms may be taken account using (Ca/Re) as a parameter. The numerical results agreed with the experimental data, provided that Marangoni effects of impurities are taken into account. The results allow the determination of slug length from pressure drop measurements in closed equipment where the slug length cannot otherwise be measured easily, such as monoliths and microreactors. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Static decouplers for control of multivariable processes
Authors: Lee Jietae , Hyun Kim Dong , Edgar Thomas F.
Published: July 2005

Decouplers can be used to improve performances of multiloop control systems by compensating for process interactions, but they are sensitive to process changes and require fairly detailed process models, which are hard to obtain. These disadvantages of decouplers hinder their successful applications in industry. On the other hand, static decouplers can be designed from process steady‐state gains, which are easier to obtain and can be tuned in the field. However, static decouplers can introduce undesirable effects on loop interactions at high frequencies for some processes. Here it is shown that static decouplers are better applied to the integral control modes for such processes. Because the integral mode is dominant at low frequencies and its magnitude decreases as frequency increases, the static decoupler implemented only on the integral mode will not disturb the frequency response of a control system at high frequencies. A simple antireset windup scheme, guaranteeing given control performances under process input saturations or failures, is provided. For online tuning of the proposed control system, a closed‐loop identification method to find process steady‐state gains is also presented. © 2005 American Institute of Chemical Engineers AIChE J, 2005
A Bayesian Hierarchical Non‐Linear Regression Model in Receiver Operating Characteristic Analysis of Clustered Continuous Diagnostic Data
Authors: Zou Kelly H. , O'Malley A. James
Published: July 2005

Receiver operating characteristic (ROC) analysis is a useful evaluative method of diagnostic accuracy. A Bayesian hierarchical nonlinear regression model for ROC analysis was developed. A validation analysis of diagnostic accuracy was conducted using prospective multi‐center clinical trial prostate cancer biopsy data collected from three participating centers. The gold standard was based on radical prostatectomy to determine local and advanced disease. To evaluate the diagnostic performance of PSA level at fixed levels of Gleason score, a normality transformation was applied to the outcome data. A hierarchical regression analysis incorporating the effects of cluster (clinical center) and cancer risk (low, intermediate, and high) was performed, and the area under the ROC curve (AUC) was estimated. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
EST sequencing for gene discovery in Chinese hamster ovary cells
Authors: Wlaschin Katie Fraass , Nissom Peter Morin , Gatti Marcela de Leon , Ong Peh Fern , Arleen Sanny , Tan Kher Shing , Rink Anette , Cham Breana , Wong Kathy , Yap Miranda , Hu Wei‐Shou
Published: July 2005

Chinese hamster ovary (CHO) cells are one of the most important cell lines in biological research, and are the most widely used host for industrial production of recombinant therapeutic proteins. Despite their extensive applications, little sequence information is available for molecular based research. To facilitate gene discovery and genetic engineering, two cDNA libraries were constructed from three CHO cell lines grown under various conditions. The average insert size for both libraries is approximately 800–850 bp, and each library has comparable redundancy levels of 36%–38% for the sequences isolated. Random sequencing of 4,608 ESTs yielded 2,602 unique assemblies, 76% of which were annotated as orthologs of sequences in the GenBank database. A high abundance of mitochondrial genome transcripts facilitated the assembly of the complete mitochondrial genome by PCR walking. Comparative analysis of sequences from both mitochondrial and nuclear genomes with orthologous genes from other species shows that CHO sequences are generally most similar to mouse; however, examples with highest similarity to rat or human are common. A cDNA microarray, including all 4,608 ESTs, was constructed. The microarray results reveal a high level of consistency between transcript abundance in the libraries and fluorescence intensities. Inclusion of redundant clones in the microarray, additionally, allows small changes in abundant mRNAs to be discerned with a high degree of confidence. The information and tools generated provide access to genomic technology for this important cell line. © 2005 Wiley Periodicals, Inc.
Coexpression of the type I signal peptidase gene sipM increases recombinant protein production and export in Bacillus megaterium MS941
Authors: Malten Marco , Nahrstedt Hannes , Meinhardt Friedhelm , Jahn Dieter
Published: July 2005

The removal of the signal peptide from a precursor protein is a crucial step of protein secretion. In order to improve Bacillus megaterium as protein production and secretion host, the influence of homologous type I signal peptidase SipM overproduction on recombinant Leuconostoc mesenteroides dextransucrase DsrS synthesis and export was investigated. The dsrS gene was integrated as a single copy into the chromosomal bgaM locus encoding β‐galactosidase. Desired clones were identified by blue‐white selection. In this strain, the expression of sipM from a multicopy plasmid using its own promoter increased the amount of secreted DsrS 3.7‐fold. This increase in protein secretion by SipM overproduction was next transferred to a high level DsrS production strain using a multicopy plasmid encoding sipM with its natural promoter and dsrS under control of a strong xylose‐inducible promoter. No further increase in DsrS export were observed when this vector was carrying two sipM copies. Similarly, bicistronic sipM and dsrS high level expression did not enhance DsrS secretion, indicating the natural limitation of the approach. Interestingly, SipM‐enhanced DsrS secretion also resulted in an overall increase of DsrS production. © 2005 Wiley Periodicals, Inc.
Prospective nationwide analysis of laparoscopic versus Lichtenstein repair of inguinal hernia
Authors: Wara P , Bay-Nielsen M , Juul P , Bendix J , Kehlet H
Published: July 2005

Background

According to a Cochrane review, laparoscopic inguinal hernia repair compares favourably with open mesh repair, but few data exist from surgical practice outside departments with a special interest in hernia surgery. This study compared nationwide reoperation rates after laparoscopic and Lichtenstein repair, adjusting for factors predisposing to recurrence.

Methods

Some 3606 consecutive laparoscopic repairs were compared with 39 537 Lichtenstein repairs that were prospectively recorded in a nationwide registry between 1998 and 2003. Patients were subgrouped according to type of hernia: primary or recurrent and unilateral or bilateral. Overall reoperation rates and 95 per cent confidence intervals were calculated. Long-term reoperation rates were estimated using the Kaplan–Meier method.

Results

The overall reoperation rates after laparoscopic and Lichtenstein repair of unilateral primary indirect hernia (0 versus 1·0 per cent), primary direct hernia (1·1 versus 3·1 per cent), unilateral recurrent hernia (4·6 versus 4·8 per cent) and bilateral recurrent hernia (2·6 versus 7·6 per cent) did not differ. However, laparoscopic repair of a bilateral primary hernia was associated with a higher reoperation rate than Lichtenstein repair (4·8 versus 3·0 per cent) (P = 0·017).

Conclusion

Laparoscopic repair compared favourably with Lichtenstein repair for primary indirect and direct hernias, and unilateral and bilateral recurrent hernias, but was inferior for primary bilateral hernias.
Design Optimization of a Spray Chamber for Plasma Spectrometry using Computational Fluid Dynamics and an Evolution Strategy
Authors: Schaldach G. , Berger L. , Razilov I. , Berndt H. , Werner U.
Published: July 2005

Spectroscopy with inductively coupled plasmas is a widespread method in analytical chemistry for the determination of trace elements in various materials. The samples to be investigated are transferred into solutions. A nebulizer then generates an aerosol of fine droplets. The aerosol has to be conditioned in a spray chamber before it can be introduced into the plasma. All spray chambers used today have been developed empirically. In this work for the first time ever, a spray chamber has been optimized with the aid of computational fluid dynamics in combination with an evolutionary strategy.
Local Velocity and Concentration of the Single Components in Water/Oil Mixtures Monitored by Means of MRI Flow Experiments in Steady Tube Flow
Authors: Götz J. , Zick K.
Published: July 2005

In this paper the spatially resolved determination of velocities in two‐phase systems consisting of water and oil by means of nuclear magnetic resonance (NMR) imaging (MRI) techniques is described and applied to steady tube flows with regard to the total flow rate. As MRI offers the possibility to study the flow of multiphase materials spatially resolved with various forms of contrast, even optically opaque water/oil mixtures can be studied in the interior of the material. Besides snapshot images of the actual flow pattern also local velocity and concentration fields of both phases can be obtained separately. The insight into the inner micro flow processes and microstructure allows to characterize fluid mixtures or emulsions. Flow rate and preparation/mixing method were varied in order to realize changes of the flow pattern and the structure of the mixture during flow. Physical models of the flow behavior and physical stability of these complex systems can be based upon this information.
Catalytic Oxidation of Methanol to Formaldehyde in a Continuous Fluidized‐Bed Reactor
Authors: Sohrabi M. , Aghdasinia H.
Published: July 2005

Partial oxidation of methanol to formaldehyde by using a mixture of ferric and molybdenum oxides as the reaction catalyst at 280–330 °C has been studied in a continuous fluidized bed reactor. The reactor was a cylindrical tube of 20 mm in i.d. and 36 mm in o.d. placed vertically and connected to a truncated coneshaped cyclone separator. The catalyst was prepared by the precipitation method using aqueous solutions of ammonium heptamolybdate and ferric nitrate. The effect of certain parameters, such as temperature, superficial gas velocity and feed flow rates, on the extent of oxidation reaction has been investigated. The maximum size of the catalyst particles was 990 μm, therefore, neither external nor internal diffusion was expected to be effective in the process. The experimental data were correlated with three classes of hydrodynamic models presented for fluidized systems. The best correlation was obtained with compartment type models.
Effect of Ethylene Glycol on the CO2/Water Gas‐Liquid Mass Transfer Process
Authors: Gómez‐Díaz D. , Navaz J. M.
Published: July 2005

The effect caused by the presence of ethylene glycol on the gas‐liquid mass transfer velocity of CO2 in a aqueous phase has been studied. In this study two different gas‐liquid contactors have been used, a bubbling stirred reactor and a flat surface stirred vessel. The first contactor, gas phase, was introduced using a porous bubbling plate. The influence of operational variables, stirring rate, gas flow rate and ethylene glycol concentration were studied. The experiments were carried out at 298.15 K using a semicontinuous regime. The final aim was to obtain empirical equations that allow the calculation of the mass transfer velocity for this system a priori.