bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Ryanodine Receptor–mediated Calcium Release in Human B Cells
Authors: McKinney Leslie C. , Butler Thomas , Mullen Shawn P. , Klein Michael G.
Published: May 2006

Background

Mutations in the ryanodine type 1 receptor (RyR1) are causative for malignant hyperthermia. Studies in human B lymphocytes have shown that measurement of RyR1-mediated intracellular Ca(2+) (Ca(2+)(i)) release can differentiate between normal and malignant hyperthermia-susceptible individuals. The authors have further developed the B-cell assay by pharmacologically characterizing RyR1-mediated Ca release in two normal human B-cell lines and demonstrating increased sensitivity of lymphocytes to the RyR1 agonist 4-chloro-m-cresol (4-CmC) in the porcine model of MH.

Methods

Ca(2+)(i) was measured fluorometrically using fura-2 in populations of cells in suspension or with fluo-4 in single cells using confocal microscopy. The Dakiki and PP normal human B cell lines were used, as well as lymphocytes obtained from normal and malignant hyperthermia-susceptible pigs. 4-CmC was used to elicit RyR1-mediated Ca release; all experiments were performed in the absence of external Ca(2+).

Results

EC(50) values for 4-CmC were 0.98 and 1.04 mm for Dakiki and PP cells, respectively, demonstrating reproducibility. The 4-CmC-induced increase in Ca(2+)(i) was eliminated by thapsigargin and was unaffected by xestospongin C. The Ca(2+)(i) increase was separable from mitochondrial stores and was inhibited by azumolene. Caffeine did not induce Ca(2+)(i) release, but ryanodine depleted intracellular stores by 50%. Lymphocytes from pigs carrying the Arg614Cys mutation in RyR1 showed increased sensitivity to 4-CmC (EC(50) = 0.47 vs. 0.81 mm for cells derived from normal animals).

Conclusions

RyR1-mediated Ca(2+) signals can be pharmacologically distinguished from other intracellular sources in human B cells, and alterations of RyR1 function can be successfully detected using Ca(2+) release from intracellular stores as an end point.
Effect of the Physical Properties of Isoflurane, Sevoflurane, and Desflurane on Pulmonary Resistance in a Laboratory Lung Model
Authors: Nyktari Vasilia G. , Papaioannou Alexandra A. , Prinianakis George , Mamidakis Eytichis G. , Georgopoulos Dimitris , Askitopoulou Helen
Published: May 2006

Background

Airway resistance depends not only on an airway's geometry but also on flow rate, and gas density and viscosity. A recent study showed that at clinically relevant concentrations, the mixtures of volatile agents with air and oxygen and oxygen-nitrogen affected the density of the mixture. The goal of the current study was to investigate the effect of different minimum alveolar concentrations (MACs) of three commonly used volatile agents, isoflurane, sevoflurane, and desflurane, on the measurements of airway resistance.

Methods

A two-chamber fixed-resistance test lung was connected to an anesthesia machine using the volume control mode of ventilation. Pulmonary resistance was calculated at baseline (25% oxygen in air); at 1.0, 1.5, and 2.0 MAC; and also at the same concentrations, 1.2% and 4%, of isoflurane, sevoflurane, and desflurane mixtures with 25% oxygen in air. The analysis of variance test for repeated measures and probabilities for post hoc Tukey and least significant difference tests were used.

Results

Isoflurane affected pulmonary resistance only at 2 MAC. Sevoflurane caused a significant increase of pulmonary resistance at 1.5 and 2 MAC, whereas desflurane caused the greatest increase in pulmonary resistance at all MAC values used. At 1.2% concentration, no difference from the baseline resistance was observed, whereas at 4%, the three agents produced similar increases of pulmonary resistance.

Conclusion

High concentrations of volatile agents in 25% oxygen in air increased the density of the gas mixture and the calculated resistance of a test lung model with fixed resistance.
The Antibiotic Erythromycin Induces Tolerance against Transient Global Cerebral Ischemia in Rats (Pharmacologic Preconditioning)
Authors: Brambrink Ansgar M. , Koerner Ines P. , Diehl Kathrin , Strobel Georg , Noppens Ruediger , Kempski Oliver
Published: May 2006

Background

Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression.

Methods

Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later.

Results

Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged.

Conclusions

Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.
Mechanism-based Pharmacokinetic–Pharmacodynamic Modeling of the Antinociceptive Effect of Buprenorphine in Healthy Volunteers
Authors: Yassen Ashraf , Olofsen Erik , Romberg Raymonda , Sarton Elise , Danhof Meindert , Dahan Albert
Published: May 2006

Background

The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers.

Methods

Data on the time course of the antinociceptive effect after intravenous administration of 0.05-0.6 mg/70 kg buprenorphine in healthy volunteers was analyzed in conjunction with plasma concentrations by nonlinear mixed-effects analysis.

Results

A three-compartment pharmacokinetic model best described the concentration time course. Four structurally different pharmacokinetic-pharmacodynamic models were evaluated for their appropriateness to describe the time course of buprenorphine's antinociceptive effect: (1) E(max) model with an effect compartment model, (2) "power" model with an effect compartment model, (3) receptor association-dissociation model with a linear transduction function, and (4) combined biophase equilibration/receptor association-dissociation model with a linear transduction function. The latter pharmacokinetic-pharmacodynamic model described the time course of effect best and was used to explain time dependencies in buprenorphine's pharmacodynamics. The model converged, yielding precise estimation of the parameters characterizing hysteresis and the relation between relative receptor occupancy and antinociceptive effect. The rate constant describing biophase equilibration (k(eo)) was 0.00447 min(-1) (95% confidence interval, 0.00299-0.00595 min(-1)). The receptor dissociation rate constant (k(off)) was 0.0785 min(-1) (95% confidence interval, 0.0352-0.122 min(-1)), and k(on) was 0.0631 ml . ng(-1) . min(-1) (95% confidence interval, 0.0390-0.0872 ml . ng(-1) . min(-1)).

Conclusion

This is consistent with observations in rats, suggesting that the rate-limiting step in the onset and offset of the antinociceptive effect is biophase distribution rather than slow receptor association-dissociation. In the dose range studied, no saturation of receptor occupancy occurred explaining the lack of a ceiling effect for antinociception.
Parturition in the Rat
Authors: Catheline Gwénaëlle , Touquet Bastien , Besson Jean-Marie , Lombard Marie-Christine
Published: May 2006

Background

Pain during labor is a common and severe phenomenon, but its clinical management remains haphazard because its neurophysiology is poorly understood. In the current study, the authors evaluate the parturient rat as a relevant model to study the pharmacology of labor pain.

Methods

Control of birth timing in term pregnant rats was achieved by gavage with RU 486 (5 mg/kg) the day before the expected day of parturition. The behavioral events preceding the expulsion of the first pup were analyzed, and immunodetection of the c-Fos protein was used to evaluate the spinal neuronal activity at the lumbosacral level where genital and perineal inputs terminate.

Results

Hind limb and abdominal stretches occurred during labor (mean number, 57 +/- 10), arbitrarily defined as the time elapsed between the first stretch and the expulsion of the first pup (mean duration, 62 +/- 5 min). Subcutaneous oxytocin increased the frequency of stretches, accounting for the fact that these manifestations are linked to uterine contractions. Finally, epidural morphine (30 microg/10 microl) in oxytocin-treated rats, although resulting in no change of labor duration, significantly decreased the number of stretches (8 +/- 2 vs. 57 +/- 12 for epidural saline) and the number of c-Fos-positive neurons in the lumbosacral spinal segments (80 +/- 25 vs. 165 +/- 17 for epidural saline).

Conclusions

These results indicate that stretches during labor in the rat correspond to a behavioral response to nociception associated with uterine contractions and suggest that parturition in the rat could be a relevant model to investigate nociceptive mechanisms associated with parturition in women.
Differential Spinal Cord Gene Expression in Rodent Models of Radicular and Neuropathic Pain
Authors: LaCroix-Fralish Michael L. , Tawfik Vivianne L. , Tanga Flobert Y. , Spratt Kevin F. , DeLeo Joyce A.
Published: May 2006

Background

Neuropathic pain and radicular low back pain both have a major impact on human health worldwide. Microarray gene analysis on central nervous system tissues holds great promise for discovering novel targets for persistent pain modulation.

Methods

Rat models of lumbar radiculopathy (L5 nerve root ligation) and neuropathy (L5 spinal nerve transection) were used for these studies. The authors measured mechanical allodynia followed by analysis of global gene expression in the lumbar spinal cord at two time points (7 days and 14 days) after surgery using the Affymetrix RAE230A GeneChip(R) (Santa Clara, CA). The expression patterns of several genes of interest were subsequently confirmed using real-time reverse transcriptase polymerase chain reaction.

Results

The authors observed similarly robust mechanical allodynia in both models. Second, they observed significant differences in lumbar spinal cord gene expression across chronic pain models. There was little overlap between genes altered in each injury model, suggesting that the site and type of injury produce distinct spinal mechanisms mediating the observed mechanical allodynia. The authors further confirmed a subset of the genes using reverse transcriptase polymerase chain reaction and identified several genes as either neuropathy-associated genes or radiculopathy-associated genes.

Conclusions

These two models of persistent pain produce similar allodynic outcomes but produce differential gene expression. These results suggest that diverging mechanisms lead to a common behavioral outcome in these pain models. Furthermore, these distinct pathophysiologic mechanisms in neuropathic versus radicular pain may implicate unique drug therapies for these types of chronic pain syndromes.
The Nature of Satisfaction With Subordinates: Its Predictors and Importance to Supervisors
Authors: Beehr Terry A. , Glaser Katherine M. , Beehr Matthew J. , Beehr Dana E. , Wallwey Dee A. , Erofeev Dmitry , Canali Kristophor G.
Published: May 2006

Two studies examined supervisors' satisfaction with subordinates, and its predictors and importance to supervisors. Study 1 found entity relationships in the form of similarity between supervisors' and subordinates' values were uniquely related to satisfaction with subordinates. Liking of subordinates (from LMX theory) appears to link leadership and job‐satisfaction domains. In Study 2, entity relationships, functional relationships, and job performance of subordinates were related to supervisors' satisfaction with subordinates. Functional relationships were the strongest and job performance the next strongest predictors. Performance was related moderately to similarity of supervisors' and subordinates' values and functional relationships. Satisfaction with subordinates was not related to supervisors' global satisfaction and turnover intention in either study, suggesting that subordinates may not be very important to supervisors.
One‐to‐One or Group‐Based Peer Support for Breastfeeding? Women's Perceptions of a Breastfeeding Peer Coaching Intervention
Authors: Hoddinott Pat , Chalmers Maretta , Pill Roisin
Published: May 2006

Abstract:  Background:
Studies reporting one‐to‐one peer support interventions have been successful in some countries with high breastfeeding initiation rates, but less so in Great Britain, where low uptake of peer support has occurred. We conducted a peer coaching intervention study in rural Scotland that improved breastfeeding initiation and duration. This study reports qualitative data about participants’ perceptions of the coaching intervention. The aim was to investigate why group‐based peer support was more popular than one‐to‐one peer support. Methods:Qualitative data were collected and analyzed from an initial focus group; 21 semi‐structured interviews; and 31 coaching group observations and respondents (n = 105/192) in response to an open question about reasons for not choosing a personal coach in a survey of breastfeeding experiences. We developed a coding frame, identified themes, and constructed charts for analysis and interpretation of data. Results:Analysis revealed that groups were more popular because they normalized breastfeeding in a social environment with refreshments, which improved participants’ sense of well‐being. Groups provided flexibility, a sense of control, and a diversity of visual images and experiences, which assisted women to make feeding‐related decisions for themselves, and they offered a safe place to rehearse and perform breastfeeding in front of others, in a culture where breastfeeding is seldom seen in public. Women often felt initial anxiety when attending a group for the first time, and they expressed doubt that one set of “breastfeeding rules” would suit everyone. Conclusions:Pregnant women and breastfeeding mothers will voluntarily engage in an activity to support breastfeeding if there is a net interactional (verbal, visual, emotional and gustatory) gain and a minimum risk of a negative experience. One‐to‐one peer coaching was perceived as a greater risk to confidence and empowerment than group‐ based peer coaching. (BIRTH 33:2 June 2006)
Why Do Women Go Along with This Stuff?
Authors: Kitzinger Sheila , Green Josephine M. , Chalmers Beverley , Keirse Marc J.N.C. , Lindstrom Kathleen , Hemminki Elina
Published: May 2006

PREFACE:  Normal childbirth has become jeopardized by inexorably rising interventions around the world. In many countries and settings, cesarean surgery, labor induction, and epidural analgesia continue to increase beyond all precedent, and without convincing evidence that these actions result in improved outcomes (1,2). Use of electronic fetal monitoring is endemic, despite evidence of its ineffectiveness and consequences for most parturients (1,3); ultrasound examinations are too often done unnecessarily, redundantly, or for frivolous rather than indicated reasons (4); episiotomies are still routine in many settings despite clear evidence that this surgery results in more harm than good (5); and medical procedures, unphysiological positions, pubic shaving and enemas, intravenous lines, enforced fasting, drugs, and early mother‐infant separation are used unnecessarily (1). Clinicians write and talk about the ideal of evidence‐based obstetrics, but do not practice it consistently, if at all.

Why do women go along with this stuff? In this Roundtable Discussion, Part 1, we asked some maternity care professionals and advocates to discuss this question. (BIRTH 33:2 June 2006)
Bonfils semirigid endoscope for guidance during percutaneous tracheostomy
Authors: Buehner U. , Oram J. , Elliot S. , Mallick A. , Bodenham A.
Published: May 2006

We report on the use of the Bonfils semirigid scope for endoscopic guidance during percutaneous dilational tracheostomy. Forty patients requiring percutaneous dilational tracheostomy on the General or Neurosurgical Intensive Care Unit were enrolled in this study. We used the ‘45 degree curved distal tip’ scope in the first 15 patients, evaluating its ease of use, optical quality of focus and image resolution as well as light intensity on a 10‐point scale. We evaluated straight and curved versions of it in another 15 and 10 patients, respectively. We examined the impact on ventilation and cardiovascular parameters. In all patients (n = 40) visualisation of the procedure was satisfactory. There were no clinically significant changes in ventilatory or cardiovascular parameters. The image quality for most patients received a score of 7–10. The Bonfils scope provides a practical alternative to flexible bronchoscopes in this setting.
Learning and performance of tracheal intubation by novice personnel: a comparison of the Airtraq® and Macintosh laryngoscope
Authors: Maharaj C. H. , Costello J. F. , Higgins B. D. , Harte B. H. , Laffey J. G.
Published: May 2006

Direct laryngoscopic tracheal intubation is taught to many healthcare professionals as it is a potentially lifesaving procedure. However, it is a difficult skill to acquire and maintain, and, of concern, the consequences of poorly performed intubation attempts are potentially serious. The Airtraq® Laryngoscope is a novel intubation device which may possess advantages over conventional direct laryngoscopes for use by novice personnel. We conducted a prospective trial with 40 medical students who had no prior airway management experience. Following brief didactic instruction, each participant took turns in performing laryngoscopy and intubation using the Macintosh and Airtraq devices under direct supervision. Each student was allowed up to three attempts to intubate in three laryngoscopy scenarios using a Laerdal® Intubation Trainer and one scenario in a Laerdal® SimMan® Manikin. They then performed tracheal intubation of the normal airway a second time to characterise the learning curve for each device. The Airtraq provided superior intubating conditions, resulting in greater success of intubation, particularly in the difficult laryngoscopy scenarios. In both easy and simulated difficult laryngoscopy scenarios, the Airtraq decreased the duration of intubation attempts, reduced the number of optimisation manoeuvres required, and reduced the potential for dental trauma. The Airtraq device showed a rapid learning curve and the students found it significantly easier to use. The Airtraq appears to be a superior device for novice personnel to acquire the skills of tracheal intubation.
The status of new anticoagulants
Authors: Bates Shannon M. , Weitz Jeffrey I.
Published: May 2006

Currently available anticoagulants include heparin, low‐molecular weight heparin, fondaparinux and warfarin. Despite advances with low‐molecular weight heparin and fondaparinux, the currently available agents have limitations that have provided the impetus for the development of new drugs for prevention and treatment of both venous and arterial thromboembolism. Novel anticoagulants targeting specific steps in coagulation are in various stages of development. This paper reviews the pharmacology of these new agents and describes the results of clinical trials with new anticoagulants in more advanced stages of clinical testing.
Evidence for a lacustrine faunal refuge in the Larsemann Hills, East Antarctica, during the Last Glacial Maximum
Authors: Cromer Louise , Gibson John A. E. , Swadling Kerrie M. , Hodgson Dominic A.
Published: May 2006

Aim  There is no previous direct evidence for the occurrence of lacustrine refuges for invertebrate fauna in Antarctica spanning the Last Glacial Maximum (LGM). In the absence of verified LGM lacustrine refuges many species are believed to result from Holocene dispersal from sub‐Antarctic islands and continents further north. If freshwater lake environments were present throughout the LGM, extant freshwater species may have been associated with Antarctica prior to this glacial period. This study looked at faunal microfossils in a sediment core from an Antarctic freshwater lake. This lake is unusual in that, unlike most Antarctic lakes, the sediment record extends to c. 130,000 yr bp, i.e. prior to the LGM.

Location  Lake Reid, Larsemann Hills, East Antarctica (76°23′ E; 69°23′ S).

Methods  Palaeofaunal communities in Lake Reid were identified through examination of faunal microfossils in a sediment core that extended to c. 130,000 yr bp.

Results  Ephippia and mandibles from the cladoceran Daphniopsis studeri and loricae of the rotifer Notholca sp. were found at all depths in the sediment, indicating that these two species have been present in the lake for up to 130,000 years. Copepod mandibles were also present in the older section of the core, yet were absent from the most recent sediments, indicating extinction of this species from Lake Reid during the LGM.

Main conclusion  The presence of D. studeri and Notholca sp. microfossils throughout the entire Lake Reid core is the first direct evidence of a glacial lacustrine refugium for invertebrate animals in Antarctica, and indicates the presence of a relict fauna on the Antarctic continent.
Anagenetic evolution in island plants
Authors: Stuessy Tod F. , Jakubowsky Gerhard , Gómez Roberto Salguero , Pfosser Martin , Schlüter Philipp M. , Fer Tomas , Sun Byung‐Yun , Kato Hidetoshi
Published: May 2006

Aim Plants in islands have often evolved through adaptive radiation, providing the classical model of evolution of closely related species each with strikingly different morphological and ecological features and with low levels of genetic divergence. We emphasize the importance of an alternative (anagenetic) model of evolution, whereby a single island endemic evolves from a progenitor and slowly builds up genetic variation through time.

Location Continental and oceanic islands.

Methods We surveyed 2640 endemic angiosperm species in 13 island systems of the world, both oceanic and continental, for anagenetic and cladogenetic patterns of speciation. Genetic data were evaluated from a progenitor and derivative species pair in Ullung Island, Korea, and Japan.

Results We show that the anagenetic model of evolution is much more important in oceanic islands than previously believed, accounting for levels of endemic specific diversity from 7% in the Hawaiian Islands to 88% in Ullung Island, Korea, with a mean for all islands of 25%. Examination of an anagenetically derived endemic species in Ullung Island reveals genetic (amplified fragment length polymorphism) variation equal or nearly equal to that of its continental progenitor.

Main conclusions We hypothesize that, during anagenetic speciation, initial founder populations proliferate, and then accumulate genetic variation slowly through time by mutation and recombination in a relatively uniform environment, with drift and/or selection yielding genetic and morphological divergence sufficient for the recognition of new species. Low‐elevation islands with low habitat heterogeneity are highly correlated with high levels of anagenetic evolution, allowing prediction of levels of the two models of evolution from these data alone. Both anagenetic and adaptive radiation models of speciation are needed to explain the observed levels of specific and genetic diversity in oceanic islands.
YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in Escherichia coli
Authors: Malinverni Juliana C. , Werner John , Kim Seokhee , Sklar Joseph G. , Kahne Daniel , Misra Rajeev , Silhavy Thomas J.
Published: May 2006

Recent advances in the study of bacterial membranes have led to the identification of a multicomponent YaeT complex in the outer membrane (OM) of Gram‐negative bacteria that is involved in the targeting and folding of β‐barrel outer membrane proteins (OMPs). In Escherichia coli, this complex consists of an essential OMP, YaeT, and three OM lipoproteins, YfgL, NlpB and YfiO. YfiO is the only essential lipoprotein component of the complex. We show that this lipoprotein is required for the proper assembly and/or targeting of OMPs to the OM but not the assembly of lipopolysaccharides (LPS). Depletion of YfiO causes similar phenotypes as does the depletion of YaeT, and we conclude that YfiO plays a critical role in YaeT‐mediated OMP folding. We demonstrate that YfiO and YfgL directly interact with YaeT in vitro, while NlpB interacts directly with YfiO. Genetic analysis verifies the importance of YfiO and its interactions with NlpB in maintaining the functional integrity of the YaeT complex.
O3impacts on plant development: a meta‐analysis of root/shoot allocation and growth
Authors: GRANTZ D. A. , GUNN S. , VU H.‐B.
Published: May 2006

The mechanism of O3action on plants remains poorly characterized. Symptoms include visible lesions on the leaf surface, reduced growth and a hypothesized reduction in allocation of carbohydrate to roots. The generality of this latter phenomenon has not been demonstrated. Here, a meta‐analysis is performed of all available experimental data, to test the hypotheses that O3exposure of the shoot inhibits biomass allocation below ground (the root/shoot allometric coefficient,k) and inhibits whole‐plant growth rate [relative growth rate (RGR)]. Bothkand RGR were significantly reduced by O3(5.6 and 8.2%, respectively). Variability inkwas greater than in RGR, and both exhibited some positive as well as mostly negative responses. The effects onkwere distinct from the effects on RGR. In some cases,kwas reduced while RGR was unaffected. Slow‐growing plants (small RGR) exhibited the largest declines ink. These observations may have mechanistic implications regarding O3phytotoxicity. There were no effects of type of exposure chamber on sensitivity to O3. The analyses indicate that the O3inhibition of allocation to roots is real and general, but variable. Further experiments are needed for under‐represented plant groups, to characterize exceptions to this generalization and to evaluate O3–environment interactions.
A role for ethylene in the phytochrome‐mediated control of vegetative development
Authors: Foo Eloise , Ross John J. , Davies Noel W. , Reid James B. , Weller James L.
Published: May 2006

Members of the phytochrome family of photoreceptors play key roles in vegetative plant development, including the regulation of stem elongation, leaf development and chlorophyll accumulation. Hormones have been implicated in the control of these processes in de‐etiolating seedlings. However, the mechanisms by which the phytochromes regulate vegetative development in more mature plants are less well understood. Pea (Pisum sativum) mutant plants lacking phytochromes A and B, the two phytochromes present in this species, develop severe defects later in development, including short, thick, distorted internodes and reduced leaf expansion, chlorophyll content and CAB gene transcript level. Studies presented here indicate that many of these defects in phyA phyB mutant plants appear to be due to elevated ethylene production, and suggest that an important role of the phytochromes in pea is to restrict ethylene production to a level that does not inhibit vegetative growth. Mutant phyA phyB plants produce significantly more ethylene than WT plants, and application of an ethylene biosynthesis inhibitor rescued many aspects of the phyA phyB mutant phenotype. This deregulation of ethylene production in phy‐deficient plants appears likely to be due, at least in part, to the elevated transcript levels of key ethylene‐biosynthesis genes. The phytochrome A photoreceptor appears to play a prominent role in the regulation of ethylene production, as phyA, but not phyB, single‐mutant plants also exhibit a phenotype consistent with elevated ethylene production. Potential interactions between ethylene and secondary plant hormones in the control of the phy‐deficient mutant phenotype were explored, revealing that ethylene may inhibit stem elongation in part by reducing gibberellin levels.
Spatio‐temporal accumulation of microRNAs is highly coordinated in developing plant tissues
Authors: Válóczi Anna , Várallyay Éva , Kauppinen Sakari , Burgyán József , Havelda Zoltán
Published: May 2006

MicroRNAs (miRNAs) are an abundant class of small, endogenous non‐protein‐coding RNAs, approximately 21 nucleotides in length, that modulate the expression of animal and plant target genes at the post‐transcriptional level. Recent work has shown that miRNA‐based gene regulation plays a crucial role in pathways involved in plant growth and development. However, knowledge about the timing and spatial regulation of plant miRNA expression is still limited. Here we usedin situanalysis to demonstrate that miRNAs accumulate spatially and temporally in a highly restricted manner inNicotiana benthamianaandArabidopsis thaliana. The presence of the seven investigated miRNAs was characteristic of the developing organs, implying a role in cell‐fate establishment, differentiation and cell‐cycle progression. Spatial analyses revealed that six of the studied miRNAs were present in vascular bundles, suggesting that mobile miRNAs in the phloem could contribute to the coordination of organogenesis and development. The obvious absence of miR167 in vascular bundles represented an exception to this observation, implying an active process in regulating the presence of miRNAs in the vascular system. Taken together, our results imply that the spatially and temporally organized accumulation of miRNAs plays a pivotal role in fine‐tuning of target gene expression in plant development.
Heterogeneous expression of melanoma antigen (hMAGE) mRNA in mesenchymal neoplasia
Authors: Joyner D. E. , Damron T. A. , Aboulafia A. , Bokor W. , Bastar J. D. , Randall R. L.
Published: May 2006

Recommendations have been advanced recently for the use of cancer/testis (CT) immunotherapy against sarcomas. CT antigens are encoded by cancer‐germline genes (e.g., hMAGE family) that are expressed in tumors and male germline cells but typically not in normal tissues. At present, little information is available regarding CT expression in mesenchymal neoplasms, and it remains uncertain whether CT immunotherapy will serve as a viable alternative or adjunct to current sarcoma therapies involving resection, followed by adjuvant radiotherapy and/or chemotherapy. In this study, hMAGEA2, hMAGEA3, hMAGEA4, and hMAGEC1 mRNA content in 21 benign mesenchymal tumors (representing seven histotypes) and 28 primary sarcomas (10 histotypes) was inventoried using real‐time‐PCR and then compared against hMAGE mRNA expression in non‐sarcomatous malignancies, three cell lines, and muscle. hMAGEA2, hMAGEA3, and hMAGEC1 transcripts were infrequent in mesenchymal tissues in general, whereas hMAGEA4 mRNA was present in 84% of all mesenchymal tumors, 100% of non‐sarcomatous tumors, all three cell lines, and in four of five muscle samples. Although hMAGEA4 mRNA was detected in four of five muscle preparations, there was no indication that the mRNA was translated into protein. The presence of hMAGEA4 mRNA in muscle, plus the inconsistent and infrequent occurrence of hMAGEA2, hMAGEA3, and hMAGEC1 mRNA within and among mesenchymal tumor histotypes, makes these four hMAGE antigens unlikely candidates for sarcoma‐specific immunotherapy.
The genetic basis of intrinsic and extrinsic post-zygotic reproductive isolation jointly promoting speciation in the lake whitefish species complex (Coregonus clupeaformis)
Authors: Rogers S. M. , Bernatchez L.
Published: May 2006

Understanding the genetic architecture of reproductive barriers and the evolutionary forces that drove their divergence represents a considerable challenge towards understanding speciation. The objective of this study was to determine the genetic basis of intrinsic and extrinsic post-zygotic isolation in diverging populations of dwarf and normal lake whitefish with allopatric glacial origins. We found that the rate of embryonic mortality was 5.3–6.5 times higher in dwarf-normal hybrid backcrosses during development than in F1 dwarf and normal crosses. When comparing embryos that died during development against larvae that successfully hatched, patterns of Mendelian segregation at 101 loci whose linkage is known identified 13 loci distributed over seven linkage groups that exhibited significant shifts in segregation ratios leading to significant segregation distortion at these loci in the surviving progeny. Controlled crosses and quantitative trait loci analysis revealed a significant genetic basis for developmental time until emergence, a trait critical to fish larval survival in nature. Hatching backcross progeny exhibited asynchronous emergence and transgressive segregation, suggesting that extrinsic post-zygotic isolation may select against hybridization in specific environmental contexts. Evidence of a genetic basis for increased embryonic mortality followed by asynchronous emergence indicated that intrinsic and extrinsic mechanisms are not mutually exclusive in the formation and maintenance of reproductive isolation, but may be jointly promoting population divergence and ultimately speciation.
Time Delay, Temperature Effects and Assessment of Positive Controls on Whole Blood for the Gamma Interferon ELISA to Detect Paratuberculosis
Authors: Robbe‐Austerman S. , Krull A. C. , Stabel J. R.
Published: May 2006

Our objective was to evaluate the effects of time and temperature on whole blood used in the gamma interferon enzyme‐linked immunosorbent assay (IFN‐γ ELISA) for paratuberculosis along with evaluating four potential positive controls, and four different mycobacterial antigens for the ELISA. Nine adult Holstein cattle naturally infected with Mycobacterium avium ssp. paratuberculosis were used in a randomized complete block design. Forty‐nine blood tubes were collected from each animal and held at 48.9, 37.8, 26.7, 21.1, 15.6 and 4.4°C for 0, 4, 8, 12, 18, 24, 32, 48 and 72 h. Each blood tube was tested with four mycobacterial antigens (two johnin PPDs, an avain PPD and a whole cell sonicate) and four potential positive controls [concanavalin A (conA), phytohaemagglutinin A (PHA), pokeweed mitogen (PWM) and Staphylococcus enterotoxin A (SEA)]. After incubation for 24 h, the plasma was assayed with a commercial IFN‐γ ELISA. Blood stored at 21.1 and 15.6°C maintained the highest ELISA optical densities (OD) over time with severe reduction in OD values at or above 37.8°C. None of the potential positive controls exactly mimicked the antigen response. SEA and PWM were able to elicit a response after the whole blood quit responding to the antigen and conA underestimated the responsiveness. Phytohemagglutinin A was similar to the antigens on an average, but there was significant disagreement among samples. The PPDs were more potent at stimulating IFN‐γ production than the whole cell sonicate. In conclusion, whole blood should be stored/transported at ambient room temperature and stimulated within 12 h of collection.
Detection of Swine Torque Teno Virus in Italian Pig Herds
Authors: Martelli F. , Caprioli A. , Di Bartolo I. , Cibin V. , Pezzotti G. , Ruggeri F. M. , Ostanello F.
Published: May 2006

Anellovirus is a recently created, floating genus of viruses. Torque teno virus (TTV), the type species in the genus, was first discovered in a human patient with a post‐transfusion hepatitis of unknown aetiology. Recently, TTV genetically related to but distinct from those discovered in humans have also been found in animals, including pigs. The aims of this study were to estimate the prevalence of swine TTV in Italian pig herds and some risk factors possibly associated with this infection. Serum samples from 179 healthy pigs from 10 farms located in north‐central Italy were tested by polymerase chain reaction for the presence of swine TTV DNA. Viral DNA was found in the sera of 43 pigs (24.0%), coming from eight of the 10 farms examined. Prevalence was significantly higher in finishing herds (40.1%) than in farrow‐to‐finish herds (11.0%) and did not depend on the size of the herd. Within the finishing herds the prevalence was significantly higher in weaners (57.4%) than in fatteners (22.9%), but this difference was not observed in farrow‐to‐finish herds. No relationship was observed between the prevalence of swine TTV and the implementation of some general hygiene practices and biosecurity procedures within the herds.
Analysis of generation means and components of variance for parthenocarpy in cucumber (Cucumis sativus L.)
Authors: Sun Z. , Lower R. L. , Staub J. E.
Published: May 2006

Parthenocarpy (seedless fruit) has potential for increasing yield in cucumber (Cucumis sativus var. sativus L.). To determine the inheritance of parthenocarpy in gynoecious cucumber, P1, P2, F1, F2, BC1P1, and BC1P2 generations derived from crossing two non‐parthenocarpic gynoecious inbred lines [Gy8 (P2; processing type) and ‘Marketmore 80’ (P2; MM, fresh market type)] with a highly parthenocarpic inbred line [2A (P1; processing type)] were evaluated for fruit number in a greenhouse at Arlington, Wisc. in 1999 (designated 2A × Gy8 1999) and in the open‐field at Hancock, Wisc. in 2000 (designated 2A × Gy8 2000 and 2A × MM 2000). There were significant location and location × generation interaction effects, and therefore generation means analyses were conducted separately for each location. The minimum numbers of effective factors controlling parthenocarpy were estimated to be at least one (2A × Gy8 1999), two (2A × Gy8 2000) and four (2A × MM 2000). Results suggest that selection for parthenocarpy for multiple hand harvest operations will likely be more effective than that for once‐over machine harvest operations. However, the selection efficiency will likely vary across different populations and environments.
Value of low‐dose 2 × 2 Gy palliative radiotherapy in advanced low‐grade non‐Hodgkin’s lymphoma
Authors: Ng M , Wirth A , Ryan G , MacManus M , Davis S
Published: May 2006

Low‐dose radiotherapy over the last decade has been reported to provide effective palliation for patients with low‐grade non‐Hodgkin’s lymphoma. In this retrospective case series of 10 patients, we report our early experience using low‐dose radiotherapy (usually 2 × 2 Gy) for patients with advanced‐stage follicular, mucosal associated lymphoid tissue, mantle cell and small lymphocytic lymphomas. Median follow up was 27 weeks. Response rates were high (complete response, 70%; partial response, 20%), the response durable and the toxicity was minimal (no toxicity greater than grade 1). Low‐dose irradiation is an effective treatment option for patients with low‐grade lymphomas with local symptoms.
Leptomeningeal carcinomatosis from perineural invasion of a lip squamous cell carcinoma
Authors: Sullivan LM , Smee R
Published: May 2006

Perineural invasion resulting in leptomeningeal carcinomatosis is a rare, but well‐recognized phenomenon in head and neck carcinomas. We report the rare case of a patient with a squamous cell carcinoma of the lip resulting in leptomeningeal carcinomatosis and review the relevant published work. A 51‐year‐old man presented with progressive facial paraesthesia after treatment for a recurrent squamous cell carcinoma of the lower lip. Cavernous sinus involvement was confirmed on MRI and he received stereotactic radiotherapy. He subsequently developed progressive lower limb neurological signs. An MRI showed multiple enhancing leptomeningeal nodules in the cervical and lumbar spine consistent with leptomeningeal carcinomatosis. Whole spine radiotherapy and dexamethasone resulted in short‐term stabilization of symptoms only and he rapidly succumbed to progressive neurological disease. To our knowledge, this is the first published report of a squamous cell carcinoma of the lip resulting in leptomeningeal disease of the cauda equina. It illustrates the potential aggressive natural history of squamous cell carcinomas with perineural invasion.
Influence of 18F‐fluorodeoxyglucose‐positron emission tomography on computed tomography‐based radiation treatment planning for oesophageal cancer
Authors: Everitt C , Leong T
Published: May 2006

The addition of positron emission tomography (PET) information to CT‐based radiotherapy treatment planning has the potential to improve target volume definition through more accurate localization of the primary tumour and involved regional lymph nodes. This case report describes the first patient enrolled to a prospective study evaluating the effects of coregistered positron emission tomography/CT images on radiotherapy treatment planning for oesophageal cancer. The results show that if combined positron emission tomography/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone. For this patient, a geographic miss of tumour would have occurred if CT data alone were used for radiotherapy planning.
Insulin‐like growth factor‐1 and TNF‐α regulate autophagy through c‐jun N‐terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells
Authors: Jia Guanghong , Cheng Gang , Gangahar Deepak M , Agrawal Devendra K
Published: May 2006

A balance between programmed cell death and survival of vascular smooth muscle cells (VSMC) in the fibrous cap, which is primarily composed of VSMC and extracellular matrix, appears to best correlate with plaque instability or stability and is controlled by growth factors and cytokines. Autophagy is also involved in programmed cell death. We assessed the effect of TNF‐α and insulin‐like growth factor‐1 (IGF‐1) on the expression of autophagic genes, microtubule‐associated protein 1 light chain 3 (MAPLC‐3) and Beclin‐1 in VSMC isolated from atherosclerotic plaques. Transmission electron microscopy showed a significantly higher number of vacuolated cells in the TNF‐α‐treated VSMC and a markedly lower number in the IGF‐1‐treated VSMC when compared with the untreated control group. TNF‐α‐induced MAPLC‐3 mRNA expression through c‐jun N‐terminal kinase and protein kinase B pathways and induced Beclin‐1 protein expression through the c‐jun N‐terminal kinase pathway. Expression of MAPLC‐3 and Beclin‐1 correlated with autophagic cell death of plaque VSMC. IGF‐1 inhibited MAPLC‐3 mRNA transcripts through the Akt pathway. These findings suggest that the expression of autophagy genes can be influenced by IGF‐1 and TNF‐α through c‐jun N‐terminal kinase or Akt pathways and autophagy might be involved in the regulation of plaque stability.
Genetic polymorphisms of the uridine diphosphate glucuronosyltransferase 1A7 and colorectal cancer risk in relation to cigarette smoking and alcohol drinking in a Chinese population
Authors: CHEN KUN , JIN MINGJUAN , ZHU YIMIN , JIANG QINTING , YU WEIPING , MA XINYUAN , YAO KAIYAN
Published: May 2006

Background:  The impact of uridine diphosphate glucuronosyltransferase 1A7 (UGT1A7) polymorphisms on genetic susceptibility to digestive system cancer has received close attention since the discovery by Guillemette, the polymorphisms of which may alter enzyme activity. To clarify the allele frequency distribution and its association with risk of colorectal cancer, a population‐based case–control study was carried out in Chinese population.

Methods:  A total of 140 patients with colorectal cancer and 280 cancer‐free frequency‐matched controls from a follow‐up cohort population established in 1989, were enrolled. For the UGT1A7 polymorphisms analysis, polymerase chain reaction (PCR)‐based genotyping techniques including semi‐nested PCR, allele‐specific PCR and PCR‐restriction fragment length polymorphism (RFLP) were developed.

Results:  The variant allele frequencies in patients and controls were 50.0% and 38.6%, respectively, which were significantly associated with risk of colorectal cancer (odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.19–2.13). For the variant genotypes analysis, *2/*2 and *3/*3 exhibited a significant association with risk of colorectal cancer (OR: 7.80, 95%CI: 2.66–22.87; OR: 3.47, 95%CI: 1.51–7.97, respectively). Stratification analysis indicated that in previous–current cigarette smoking (cigarette smoking history), current cigarette smoking (current cigarette smoking status), previous–current alcohol drinking (alcohol drinking history) or current alcohol drinking individuals (current alcohol drinking status), the risk developing colorectal cancer increased: OR (95%CI), 2.81 (0.97–8.11), 3.39 (1.19–9.67), 2.89 (0.99–8.46) and 3.14 (1.09–9.09), respectively.

Conclusions:  UGT1A7 polymorphisms may have a significant modifying effect on colorectal cancer risk, which may interact with environmental factors, cigarette smoking and alcohol drinking in colorectal carcinogenesis.
Erythrocyte Lewis (A+B–) host phenotype is a factor with familial clustering for increased risk of Helicobacter pylori‐related non‐cardiac gastric cancer
Authors: SHEU MING‐JEN , YANG HSIAO‐BAI , SHEU BOR‐SHYANG , CHENG HSIU‐CHI , LIN CHING‐YIH , WU JIUNN‐JONG
Published: May 2006

Background:  The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated with the risk of gastric cancers. Because of the association of gastric cancer with familial clustering, cancer relatives were investigated as to whether they had unique distribution of Lewis phenotypes.

Methods:  The study prospectively enrolled 74 Helicobacter pylori‐positive gastric cancer patients and 100 H. pylori‐positive duodenal ulcer patients to serve as non‐cancer controls after panendoscopy. In addition, 433 family members from the 74 index cancer and 100 non‐cancer control patients were enrolled. All enrolled cases were checked for their H. pylori status and erythrocyte Lewis phenotypes, defined as Lea–b–, Lea–b+, Lea+b–, and Lea+b+ subtypes by the anti‐Lea and anti‐Leb monoclonal antibodies.

Results:  These H. pylori‐infected patients with gastric cancer had a higher rate of Lea+b– phenotype and a lower rate of Lea–b+ phenotype than the non‐cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P < 0.05). Among these H. pylori‐infected patients, the risk of the patients with Lea+b– phenotype having gastric cancer was 3.15‐fold higher as compared with those with the Lea–b+ phenotype (P = 0.02, 95% confidence interval: 1.26–7.87). The offspring and cousins of the cancer patients had a higher rate of Lea+b– phenotype as compared to either that of the spouses of cancer index patients or to that of the family members of the non‐cancer control (P < 0.05).

Conclusion:  Lea+b– phenotype of the H. pylori‐infected host could be a risk factor (with familial clustering) for gastric carcinogenesis.