bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Clean the Dirtiest Place in the Cell: Cationic Antioxidants as Intramitochondrial ROS Scavengers
Authors: Skulachev Vladimir P.
Published: September 2005

Membrane‐penetrating triphenyl alkyl phosphonium cations have been suggested for many years in our group as having the ability to measure mitochondrial potential were recently used by Murphy as vehicles to specifically target CoQ to mitochondria. As was shown in our group, the phosphonium derivative of CoQ (MitoQ) easily penetrates a planar bilayer phospholipid membrane as a cation, generating 60 mV electric potential (ΔΨ) per a 10‐fold MitoQ gradient. This means that MitoQ should be unequally distributed across the inner mitochondrial membrane, the intramitochondrial [MitoQ] = extramitochondrial [MitoQ] × 103 at 180 mV ΔΨ. In line with such a calculation, Murphy and his colleagues reported that antioxidant efficiency of MitoQ added to mitochondria or cells appears to be very much higher than of CoQ. It was found that H2O2‐induced apoptosis (Murphy) and the H2O2‐mediated bystander killing of the cultivated cells (our group) are completely arrested by pretreatement of the cells with 10‐10 ‐ 10‐8 M MitoQ. These effects indicate that MitoQ and similar compounds may be promising in treatment of heart attack, stroke and other diseases accompanied by massive apoptosis in the injured tissue. The very fact that: (i) MitoQ is not only accumulated by mitochondria but also can be regenerated in its reduced form by mitochondrial respiratory chain, (ii) it is the mitochondrial interior that produces a large portion of reactive oxygen species (ROS) in our body, and (iii) the most sensitive ROS targets are localized in the mitochondrial matrix suggest the MitoQ‐like compounds are promising tools of molecular therapy of aerobic cells. In line with this suggestion, we found that addition of MitoQ strongly improves structural and biochemical parameters of cultivated cells. As to cationic tetrapeptides, recently advertised as mitochondrially‐targeted ΔΨ ‐independent antioxidants, their effect is most probably mediated by an opioid activity inherent in some of these substances.
IUBMB Life, 57: 305‐310, 2005
Understanding and Modulating Ageing
Authors: Rattan Suresh IS , Clark Brian FC
Published: September 2005

Ageing is characterized by a progressive accumulation of molecular damage in nucleic acids, proteins and lipids. The inefficiency and failure of maintenance, repair and turnover pathways is the main cause of age‐related accumulation of damage. Research in molecular gerontology is aimed at understanding the genetic and epigenetic regulation of survival and maintenance mechanisms at the levels of transcription, post‐transcriptional processing, post‐translational modifications, and interactions among various gene products. Concurrently, several approaches are being tried and tested to modulate ageing in a wide variety of organisms. The ultimate aim of such studies is to improve the quality of human life in old age and prolong the health‐span. Various gerontomodulatory approaches include gene therapy, hormonal supplementation, nutritional modulation and intervention by free radical scavengers and other molecules. A recent approach is that of applying hormesis in ageing research and therapy, which is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. A combination of molecular, physiological and psychological modulatory approaches can realize “healthy ageing” as an achievable goal in the not‐so‐distant future.
IUBMB Life, 57: 297‐304, 2005
Are Genetically Modified Plants Useful and Safe?
Authors: Weil Jacques‐Henry
Published: September 2005

So far, plants have been genetically modified essentially to achieve resistance to herbicides, or to pathogens (mainly insects, or viruses), but resistance to abiotic stresses (such as cold, heat, drought, or salt) is also being studied. Genetically modified (GM) plants with improved nutritional qualities have more recently been developed, such as plants containing higher proportions of unsaturated fatty acids (omega‐3 and omega‐6) in their oil (to prevent cardio‐vascular diseases), or containing β‐carotene as in the golden rice (to prevent vitamin A deficiency). Possible risks for human health (such as the production of allergenic proteins), or for the environment (such as the appearance of superweeds as a result from gene flow), should be carefully studied, and a science‐based assessment of benefits vs. risks should be made on a csae by case basis, both for GM plants and for plants obtained by conventional breeding methods.
IUBMB Life, 57: 311‐314, 2005
Control of DNA Replication: Regulation and Activation of Eukaryotic Replicative Helicase, MCM
Authors: Masai Hisao , You Zhiying , Arai Ken‐ichi
Published: September 2005

DNA replication is a key event of cell proliferation and the final target of signal transduction induced by growth factor stimulation. It is also strictly regulated during the ongoing cell cycle so that it occurs only once during S phase and that all the genetic materials are faithfully duplicated. DNA replication may be arrested or temporally inihibited due to a varieties of internal and external causes. Cells have developed intricate mechanisms to cope with the arrested replication forks to minimize the adversary effect on the stable maintenance of genetic materials. Helicases play a central role in DNA replication. In eukaryotes, MCM (minichromosome maintenance) protein complex plays essential roles as a replicative helicase. MCM4‐6‐7 complex possesses intrinsic DNA helicase activity which translocates on single‐stranded DNA form 3' to 5'. Mammalian MCM4‐6‐7 helicase and ATPase activities are specifically stimulated by the presence of thymine‐rich single‐stranded DNA sequences onto which it is loaded. The activation appears to depend on the thymine content of this single‐strand, and sequences derived from human replication origins can serve as potent activators of the MCM helicase. MCM is a prime target of Cdc7 kinase, known to be essential for activation of replication origins. We will discuss how the MCM may be activated at the replication origins by template DNA, phosphorylation, and interaction with other replicative proteins, and will present a model of how activation of MCM helicase by specific sequences may contribute to selection of replication initiation sites in higher eukaryotes.
IUBMB Life, 57: 323‐335, 2005
The Thermogenic Activity of Rat Brown Adipose Tissue and Rabbit White Muscle Ca2 + ‐ATPase
Authors: de Meis Leopoldo , Oliveira Gaya M. , Arruda Ana Paula , Santos Reinaldo , Costa Rodrigo Madeiro da , Benchimol Marlene
Published: September 2005

The Ca2 + ‐ATPase (SERCA) found in vesicles derived from the sarco/endoplasmic reticulum vesicles of rats brown adipose tissue and rabbit white muscle were identified by gel electrophoresis, Western blot, electron microscopy and immunolabeling with gold particles. In both tissues, the isoform found was SERCA 1. The Ca2 + affinity of the fat SERCA 1 was different from the muscle isoform. The degree of uncoupling is estimated measuring the ratio between Ca2 + transport and ATP cleaved. In brown fat vesicles the degree of uncoupling varied depending on the Ca2 + concentration of the medium. This was not observed in vesicles derived from muscle. At all Ca2 + concentrations tested, the uncoupling was not related to Ca2 + leakage from the membrane and was far more pronounced in fat than in muscle vesicle. When a Ca2 + gradient was formed across the vesicles membrane the heat released during ATP hydrolysis varied between 22 and 26 Kcal/mol in both fat and muscle vesicles but in the absence of a gradient the heat released was 17 Kcal/mol in fat and 12 Kcal/mol in muscle. The data reported indicate that the SERCA 1 of brown adipocytes is far more thermogenic than the white muscle SERCA 1, and suggest that, in addition to storing Ca2 + inside the endoplasmic reticulum, the SERCA 1 may represent a source of heat production contributing to the thermogenic function of brown adipose tissue.
IUBMB Life, 57: 337‐345, 2005
Dual Nature of the Genome: Genes for the Individual Life and Genes for the Evolutionary Progress of the Population
Authors: Arber Werner
Published: September 2005

Biological evolution is here postulated to be driven coordinately by the products of specific evolution genes and by non‐genetic elements such as the intrinsic properties of matter and random encounter with environmental factors. Evolution genes are supposed to have their own evolutionary history in which second‐order selection was exerted at the population level. The products of evolution genes can act as generators of genetic variations and/or as modulators of the frequency of genetic variation. Three major natural strategies, each with a number of specific mechanisms contribute to the overall spontaneous production of genetic variants. Each of these three strategies contributes its own specific quality to genetic variation. The difficulties of experimentally investigating these strategies and a wider discussion of some of the postulates within the scientific community are outlined. Finally, the general relevance of the postulated duality of the genome for our world view is briefly mentioned.
IUBMB Life, 57: 263‐266, 2005
From JNK to Pay Dirt: Jun Kinases, their Biochemistry, Physiology and Clinical Importance
Authors: Karin Michael , Gallagher Ewen
Published: September 2005

The c‐Jun N‐terminal kinases (JNKs) were originally identified by their ability to phosphorylate c‐Jun in response to UV‐irradiation, but now are recognized as critical regulators of various aspects of mammalian physiology, including: cell proliferation, cell survival, cell death, DNA repair and metabolism. JNK‐mediated phosphorylation enhances the ability of c‐Jun, a component of the AP‐1 transcription factor, to activate transcription, in response to a plethora of extracellular stimuli. The JNK activation leads to induction of AP‐1‐dependent target genes involved in cell proliferation, cell death, inflammation, and DNA repair. The JNKs, which are encoded by three different Jnk loci, are now known to be regulated by many other stimuli, from pro‐inflammatory cytokines to obesity, in addition to UV‐irradiation. Targeted disruption of the Jnk loci in mice has proved to be a critical tool in better understanding their physiological functions. Such studies revealed that the JNKs play important roles in numerous cellular processes, including: programmed cell death, T cell differentiation, negative regulation of insulin signaling, control of fat deposition, and epithelial sheet migration. Importantly, the JNKs have become prime targets for drug development in several important clinical areas, including: inflammation, diabetes, and cancer.
IUBMB Life, 57: 283‐295, 2005
Bovine Spongiform Encephalopathy ‐ Some Surprises for Biochemists
Authors: Campbell Peter N.
Published: September 2005

Bovine Spongiform Encephalopathy (BSE) is typical of the dementias that affect both animals and man; Scrapie in sheep, Creutzfeldt‐Jakob disease in man. Global efforts have been made to determine the nature of the active agents in these diseases. At present the 'protein only hypothesis' of Prusiner holds. It was a surprise that a protein could per se be the active agent but other surprises for our traditional teaching of biochemistry arose. These are explained in a brief summary of our present understanding of the biochemistry of the active agents that cause the diseases.
IUBMB Life, 57: 273‐276, 2005
Jumping Genes and Shrinking Genomes ‐ Probing the Evolution of Eukaryotic Photosynthesis with Genomics
Authors: Archibald John M.
Published: September 2005

The advent of comparative genomics has revolutionized the study of the origin and evolution of eukaryotes and their organelles. Genomic analysis has revealed that the endosymbiosis that gave rise to plastids ‐ the light‐harvesting apparatus of photosynthetic eukaryotes ‐ had a profound impact on the genetic composition of the host, far beyond the contribution of cyanobacterial genes for plastid‐specific functions. Here I discuss recent advances in our appreciation of the mosaic nature of the eukaryotic nuclear genome, and the ongoing role endosymbiosis plays in shaping its content.
IUBMB Life, 57: 539‐547, 2005
Protein Splicing: Its Discovery and Structural Insight into Novel Chemical Mechanisms
Authors: Anraku Yasuhiro , Mizutani Ryuta , Satow Yoshinori
Published: September 2005

Protein splicing is a posttranslational cellular process, in which an intervening protein sequence (intein) is self‐catalytically excised out from a nascent protein precursor and the two flanking sequences (N‐ and C‐exteins) are ligated to produce two mature enzymes. This unique reaction was first discovered from studies of the structure and expression of the VMA1 gene in Saccharomyces cerevisiae. VMA1 consists of a single open reading frame and yet comprises two independent genetic information for Vma1p (a catalytic 70‐kDa subunit of the vacuolar H + ‐ATPase) and VDE (a 50‐kDa DNA endonuclease) as an in‐frame spliced insert in the gene. Subsequent studies have demonstrated that protein splicing is not unique for the VMA1 precursor and there are many operons in nature, which implement genetic information editing at protein level. To elucidate its precise reaction mechanisms from a viewpoint of structure‐directed chemistry, a series of crystal structural studies has been carried out with the use of splicing‐inactive and slowly spliceable precursors of VMA1 recombinants. One precursor structure revealed that the N‐terminal junction of the introduced extein polypeptide forms an intermediate containing a five‐membered thiazolidine ring. The other precursor structures showed spliced products with a linkage between the N‐ and C‐extein segments. This article summarizes biochemical and structural studies on a self‐catalytic mechanism for protein splicing that is triggered and terminated solely via thiazolidine intermediates with tetrahedral configurations formed within the splicing sites where proton ingress and egress are driven by balanced protonation and deprotonation.
IUBMB Life, 57: 563‐574, 2005
RNA Silencing of Cks1 Induced G2/M Arrest and Apoptosis in Human Lung Cancer Cells
Authors: Tsai Yi‐Shan , Chang Hui‐Chiu , Chuang Lea‐Yea , Hung Wen‐Chun
Published: September 2005

Cdc kinase subunit 1 (Cks1) has been shown to involve in the regulation of cell cycle progression and p27Kip1 degradation. To define the role of Cks1 in lung tumorigenesis, we examined the expression of Cks1 in human lung cancer cell lines and tested the effect of Cks1‐specific small interfering RNA (siRNA) on these cells. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and western blot analysis showed that Cks1 was highly expressed in human lung cancer cells. Transfection of Cks1 siRNA down‐regulated Cdc2 kinase activity and induced G2/M arrest in Cks1‐ overexpressing H358 lung cancer cells. Long‐term treatment of Cks1 siRNA induced caspase activation and apoptosis in H358 cells. On the contrary, Cks1 siRNA did not affect viability of normal human lung fibroblasts under the same experimental condition. Collectively, our results suggest that Cks1 participates in the steps of lung tumorigenesis and this gene may be a target for the treatment of lung cancer.
IUBMB Life, 57: 583‐589, 2005
Structural Studies on the αβ T‐cell Receptor
Authors: Ely Lauren K. , Kjer‐Nielsen Lars , McCluskey James , Rossjohn Jamie
Published: September 2005

αβ T‐cell receptor (TcR) recognition of antigenic peptides bound to the major histocompatibility complex (pMHC), is integral to the cellular immune system. Crystallographic studies over the last decade have provided significant insight into this unique trimolecular recognition event. The TcR ‐ pMHC structural information has been paralleled by biophysical studies that have further explored the emerging binding models in an attempt to answer fundamental immunological questions regarding MHC restriction, T‐cell immunodominance and TcR cross‐reactivity. However, despite the important data that has been generated regarding TcR ‐ pMHC interactions, the scope of this information is still incomplete due to the limited range of TcRs that have been studied. These limitations are primarily due to difficulties in obtaining high yields of recombinant αβ TcR for crystallographic and biophysical analysis; here we will discuss some of the protein engineering strategies that have been employed to expand the pool of recombinant TcRs suitable for crystallographic studies and the subsequent studies that have utilized these proteins.
IUBMB Life, 57: 575‐582, 2005
A Drosophila Model of Mitochondrial DNA Replication: Proteins, Genes and Regulation
Authors: Garesse Rafael , Kaguni Laurie S.
Published: September 2005

Mitochondrial biogenesis is a critical process in animal development, cellular homeostasis and aging. Mitochondrial DNA replication is an essential part of this process, and both nuclear and mitochondrial DNA mutations are found to result in mitochondrial dysfunction that leads to developmental defects and delays, aging and disease. Drosophila provides an amenable model system to study mitochondrial biogenesis in normal and disease states. This review provides an overview of current approaches to study the proteins involved in mitochondrial DNA replication, the genes that encode them and their regulation. It also presents a survey of cell and animal models under development to mimic the pathophysiology of human mitochondrial disorders.
IUBMB Life, 57: 555‐561, 2005
Role of Leptin in Modulation of Porphyromonas gingivalis Lipopolysaccharide‐induced Up‐regulation of Endothelin‐1 in Salivary Gland Acinar Cells
Authors: Slomiany Bronislaw L. , Slomiany Amalia
Published: September 2005

Leptin, a pleiotropic cytokine that regulates food intake and metabolic and endocrine responses, has emerged recently as an important regulator of mucosal inflammatory responses to bacterial infection. In this study, we report that in sublingual salivary gland acinar cells leptin plays a role in the suppression of up‐regulation in endothelin‐1 (ET‐1), induced by the LPS of a periodontopathic bacterium P. gingivalis. We show that P. gingivalis LPS detrimental effect on salivary mucin synthesis, associated with up‐regulation (3.9‐fold) in ET‐1 generation and the enhancement (3.2‐fold) in endothelin‐converting enzyme‐1 (ECE‐1) activity, was subject to a dose‐dependent suppression by leptin. The impedance by leptin of the LPS inhibitory effect on mucin synthesis was blocked by wortmannin, an inhibitor of PI3K, as well as by ERK inhibitor, PD98059. However, while the blockade of ERK led also to amplification in the impedance by leptin of the LPS‐induced expression of ECE‐1 and ET‐1, the effect was not observed in the presence of wortmannin. The findings are the first to demonstrate that leptin counters the pathological consequences of P. gingivalis infection on the synthesis of salivary mucin through the involvement in signaling events of PI3K and ERK pathways. We also show that the ERK cascade represents a critical signaling target for leptin in the LPS‐induced up‐regulation in ET‐1.
IUBMB Life, 57: 591‐595, 2005
Monoclonal Antibodies to the Thyrotropin Receptor
Authors: Ando Takao , Davies Terry F.
Published: September 2005

The thyrotropin receptor (TSHR) is a seven transmembrane G‐protein linked
glycoprotein expressed on the thyroid cell surface and which, under the regulation
of TSH, controls the production and secretion of thyroid hormone from the thyroid
gland. This membrane protein is also a major target antigen in the autoimmune
thyroid diseases. In Graves′ disease, autoantibodies to the TSHR (TSHR‐Abs)
stimulate the TSHR to produce thyroid hormone excessively. In autoimmune thyroid
failure, some patients exhibit TSHR‐Abs which block TSH action on the
receptor. There have been many attempts to generate human stimulating
TSHR‐mAbs, but to date, only one pathologically relevant human stimulating
TSHR‐mAb has been isolated. Most mAbs to the TSHR have been derived from
rodents immunized with TSHR antigen from bacteria or insect cells. These antigens
lacked the native conformation of the TSHR and the resulting mAbs were exclusively
blocking or neutral TSHR‐mAbs. However, mAbs raised against intact native
TSHR antigen have included stimulating mAbs. One such stimulating mAb has
demonstrated a number of differences in its regulation of TSHR post‐translational
processing. These
differences are likely to be reflective of TSHR‐Abs seen in Graves′ disease.
The Homogeneous Multiplexed System‐a New Method for Autoantibody Profile in Systemic Lupus Erythematosus
Authors: Zandman-Goddard Gisele , Gilburd Boris , Shovman Ora , Blank Miri , Berdichevski Svetlana , Langevitz Pnina , Shoenfeld Yehuda
Published: September 2005

Systemic lupus erythematosus (SLE) is a multi‐systemic autoimmune
disease leading to immunological aberrations and excessive multiple autoantibody
production. The aim of this study was to investigate the prevalence of
multiple autoantibodies in SLE patients utilizing the multiplex system method.

We analyzed the presence of elevated titers of anti‐Ro, anti‐La, anti‐RNP,
anti‐Sm, anti‐Jo1, anti‐centromere, anti‐Scl‐70, anti‐histone, and anti‐dsDNA
antibodies in 199 serum samples (113 SLE patients, 86 healthy donors). We
compared the type, level and number of autoantibodies and the correlation
between
the autoantibody profile and disease severity utilizing the SLEDAI score.

Elevated titers of at least one autoantibody were detected in 48% of 42 SLE
patients. Elevated titers of anti‐Ro antibodies were most commonly detected. The
distribution of specific autoantibodies was: anti‐Ro‐ 23.8%, anti‐dsDNA‐ 19%,
anti‐histone‐ 19%, anti‐RNP‐ 14.2%, anti‐La antibodies‐ 11.9%, anti‐Sm‐ 7.1%,
anti‐Scl 70‐4.7%, and anti‐centromere‐ 2.4%. Utilizing ROC analysis, the sensitivity
and specificity of anti‐DNA antibodies at a cutoff value of 34 IU/ml were 87.1% and
79.4% respectively. Elevated titers of anti‐Jo1 antibody were not detected. There
was a correlation with the titer of anti‐Ro antibodies and disease activity by the
SLEDAI score. Seven patients harbored one autoantibody only, 15 patients
harbored 2‐3 autoantibodies, 3 patients harbored 4‐5 autoantibodies, and one
patient harbored 6 autoantibodies. A correlation between the number of
autoantibodies per patient and disease severity was found. One patient with
a multitude of
autoantibodies had severe lupus and a myriad of clinical manifestations.

In conclusion, the multiplex system is specific and sensitive, provides
an autoantibody profile in a single test, and may be useful as a diagnostic
test for SLE. Elevated anti‐Ro antibodies are associated with
severe disease. An autoantibody load may be indicative of more severe disease.
Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals
Authors: Krumbiegel Doreen , Rohr Jan , Schmidtke Peter , Knuf Markus , Zepp Fred , Meyer Claudius U.
Published: September 2005

Specific functional properties of dendritic cells (DCs) have been suspected
as being responsible for the impaired specific immune responses observed in
human neonates. To analyze stimulatory requirements for the critical transition
from immature, antigen‐processing DCs to mature, antigen‐presenting DCs, we
investigated the effect of different proinflammatory mediators and antigens on
phenotype and cytokine secretion of human neonatal DCs derived from
hematopoietic progenitor cells (HPCs). Whereas single proinflammatory
mediators were unable to induce the maturation of neonatal DCs, various
combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation
of neonatal DCs documented by up‐regulation of HLA‐DR, CD83 and CD86.
Combinations of proinflammatory mediators also increased cytokine secretion
by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to
be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In
conclusion, neonatal DCs can be stimulated to express maturation as well as
costimulatory surface molecules. However, induction
of maturation requires combined stimulation with multiple proinflammatory signals.
Endometriosis and Infertility: A Multi‐cytokine Imbalance Versus Ovulation, Fertilization and Early Embryo Development
Authors: Vassiliadis S. , Relakis K. , Papageorgiou A. , Athanassakis I.
Published: September 2005

Endometriosis is tightly linked to infertility which is manifested at very
early or more advanced stages of the gestational cycle. Alteration on
the production of a great number of cytokines/growth factors can be accused
for problems on ovum maturation, fertilization or implantation. Yet, macroscopically
these stages are characterized by the inability of conception. A closer look of
the cytokinic profile during the conceptional and early gestational cycle could,
however, localize the problem and allow a therapeutic approach. In
this commentary, going through the cytokine requirement during ovulation,
fertilization and the early stages of pregnancy, it became possible to specifically
define the harmful endometriosis‐induced cytokines for each of the conceptional
and early gestational stages. Thus, regulating the levels of interferon‐γ and tumor
necrosis‐α will facilitate ovulation and fertilization, whereas adjusting
the levels of interleukin‐1β and colony stimulating gactor‐1 will facilitate implantation.
Cytokine Profile of Mouse Vaginal and Uterus Lymphocytes at Estrus and Diestrus
Authors: Lopez Maria C. , Stanley Margaret A.
Published: September 2005

It is known that sex hormones regulate IgA and IgG levels in the female
reproductive tract. Moreover, antigen presentation by uterine and vaginal epithelial
cells is also under strict hormonal control. The effect of the estrous cycle on
cytokine secretion by vaginal and uterine lymphoid cells has been examined in
mice using simultaneous staining for cytoplasmic cytokines and surface markers
after ex vivo culture with PMA/ionomycin in the presence of Brefeldin A, and flow
cytometry analysis. Two different mice strains, BALB/c and C57BL/6 mice, were
used. The most relevant finding was the increase in the proportion of vaginal cells
secreting IFN‐γ at diestrus in both strains of mice. Other cytokines (IL‐2 and IL‐4) as
well as some T cell subsets seemed to be modified in a strain dependent
fashion. Data also suggest that NK cells are at least partially responsible for
IFN‐γ secretion. Our data indicate that vaginal and uterus lymphoid cells isolated
at diestrus were in vivo activated to secrete cytokines
after ex vivo
culture. IFN‐γ seems to be the key cytokine, since it increases in both strains of mice.
Caesarean section following the Fontan procedure: two different deliveries and different anaesthetic choices in the same patient
Authors: Eid L. , Ginosar Y. , Elchalal U. , Pollak A. , Weiniger C. F.
Published: September 2005

The Fontan procedure is performed for patients with a hypoplastic right ventricle, and pregnancies following this palliative surgery are likely to increase. We present a parturient with the Fontan physiology who successfully underwent two consecutive caesarean deliveries; the first under general anaesthesia for emergency surgery and the second under regional anaesthesia for elective surgery. We suggest that pregnancy and delivery do not typically adversely affect maternal cardiac status in these patients. Attention must be paid, however, to fetal loss, prematurity, growth retardation and associated cardiac congenital malformations for which insufficient data exist in the literature in this patient population.
Transient paralysis after administration of a single dose of cyclizine
Authors: Sandhu S. , Clarke T. N. S. , Greaves D. , Ryan D. W.
Published: September 2005

Two patients with underlying neuromuscular disorders developed varying degrees of paralysis after a single dose of cyclizine, one necessitating full mechanical ventilation. These cases appear to be unique in the literature and represent an increasing spectrum of adverse reactions seen with the greater use of cyclizine.
An unusual case of early fulminant post‐traumatic fat embolism syndrome
Authors: Huber‐Lang M. , Brinkmann A. , Straeter J. , Beck A. , Gauss A. , Gebhard F.
Published: September 2005

A multiple‐injured patient developed a very early onset fulminant fat embolism syndrome that was partially masked by haemorrhagic shock. Despite early diagnosis by transoesophageal echocardiography and aggressive symptomatic treatment, there was a rapid evolution to death. Post mortem examination revealed the presence of both pulmonary and systemic fat emboli. This case highlights the ever present risk of masked fat embolism syndrome shortly after trauma.
Outer diameter and shape of paediatric tracheal tube cuffs at higher inflation pressures
Authors: Bernet V. , Dullenkopf A. , Maino P. , Weiss M.
Published: September 2005

Cuffed tracheal tubes are becoming increasingly popular in paediatric anaesthesia and intensive care medicine. To avoid cuff related complications and airway morbidity, a thorough understanding of cuff volume/pressure behaviour and management is required. In this study, the outer cuff diameter and form stability of the cuff at high cuff pressure were assessed in a series of different paediatric cuffed tracheal tubes with internal diameter of between 3.0 and 5.0 mm. The main findings were that small amounts of inflated air led to a rapid increase in cuff pressure and volume and that the outer cuff diameters increased to 2–2.5 times the age‐corresponding internal tracheal diameter following inadvertent syringe inflation. Careful cuff inflation under cuff pressure monitoring and/or automatic cuff pressure release is recommended in paediatric tracheal tube cuffs to prevent airway damage caused by manual inflation, pilot balloon compression and nitrous oxide diffusion.
Resistance and resilience of ecosystem metabolism in a flood‐prone river system
Authors: Uehlinger Urs
Published: September 2005

1. Gross primary production (GPP) and ecosystem respiration (ER) were analysed for 18 months in two reaches of the River Thur, a prealpine river in Switzerland. The upper reach at 655 m above sea level (a.s.l.) is bedrock constrained, has a high slope (0.60%) and a catchment area of 126 km2. The lower reach at 370 m a.s.l. has a more extensive hyporheic zone, a lower slope (0.17%) and a catchment of 1696 km2.  2. In both reaches, temporal patterns of stream metabolism reflected the occurrence of bed‐moving spates. Average reductions of GPP and ER by spates were 53 and 24% in the upper reach, and 37 and 14% in the lower reach, respectively. The greater resistance of ER than GPP in both reaches shifted the ecosystem metabolism towards heterotrophy (decrease of the ratio of GPP to ER (P/R)) following spates.  3. Recovery of GPP was significantly faster in the lower reach and exhibited distinct seasonal variation (positive correlation with incident light). The differences in stability (both resistance and resilience) between reaches reflected differences in geomorphic settings and disturbance regime.  4. Stepwise regression analysis was used to explore the potential influence of season, disturbance and prevailing environmental conditions on stream metabolism in each reach. Time since spate plus temperature explained 73 and 86% of variation in ER and GPP, respectively, in the upper reach and 55% of variation in ER in the lower reach. Season plus prevailing environmental conditions explained 67% of variation in GPP in the lower reach.  5. To test how the perception of stability may change with increasing scale of observation, the disturbance regimes of 12 sites were compared with the disturbance regime of the entire Thur catchment. The analysis suggests that stream metabolism at the catchment scale is far more resistant to high flow events than at the reach scale.
Drag coefficients of stream bryophytes: experimental determinations and ecological significance
Authors: Suren Alastair M. , Smart Graeme M. , Smith Rob A. , Brown Stephanie L. R.
Published: September 2005

1. Drag coefficients (CD) of bryophyte‐covered rocks were measured to see whether these differed between species. Replicate rocks, each supporting one of six bryophyte taxa, were attached to a base plate mounted on Teflon bearings in a flow tank. The drag force exerted on rocks with and without bryophyte material was measured by a strain gauge at different water velocities.

 2. The difference in CD between rocks with and without bryophyte material was calculated for each plant, and expressed as a percentage change (δCD). This varied significantly from 0 in three of the six taxa. The cushion‐shaped moss Bryum blandum increased the CD by around 10%. The moss Blindia lewinskyae and liverwort Cryptochila grandiflora decreased the CD by around 40 and 30%, respectively, presumably reflecting their streamlined growth.  3. Drag characteristics of aquatic bryophytes may help explain differences in their resistance to fast flows. Furthermore, we suggest that some aquatic bryophytes can increase substrate stability by streamlining rocks, rendering them less prone to movement.
The R1 resistance gene cluster contains three groups of independently evolving, type I R1 homologues and shows substantial structural variation among haplotypes of Solanum demissum
Authors: Kuang Hanhui , Wei Fusheng , Marano María Rosa , Wirtz Uwe , Wang Xiaoxue , Liu Jia , Shum Wai Pun , Zaborsky Jennifer , Tallon Luke J. , Rensink Willem , Lobst Stacey , Zhang Peifen , Tornqvist Carl‐Erik , Tek Ahmet , Bamberg John , Helgeson John , Fry William , You Frank , Luo Ming‐Cheng , Jiang Jiming , Robin Buell C. , Baker Barbara
Published: September 2005

Cultivated and wild potatoes contain a major disease‐resistance cluster on the short arm of chromosome V, including the R1 resistance (R) gene against potato late blight. To explore the functional and evolutionary significance of clustering in the generation of novel disease‐resistance genes, we constructed three approximately 1 Mb physical maps in the R1 gene region, one for each of the three genomes (haplotypes) of allohexaploid Solanum demissum, the wild potato progenitor of the R1 locus. Totals of 691, 919 and 559 kb were sequenced for each haplotype, and three distinct resistance‐gene families were identified, one homologous to the potato R1 gene and two others homologous to either the Prf or the Bs4 R‐gene of tomato. The regions with R1 homologues are highly divergent among the three haplotypes, in contrast to the conserved flanking non‐resistance gene regions. The R1 locus shows dramatic variation in overall length and R1 homologue number among the three haplotypes. Sequence comparisons of the R1 homologues show that they form three distinct clades in a distance tree. Frequent sequence exchanges were detected among R1 homologues within each clade, but not among those in different clades. These frequent sequence exchanges homogenized the intron sequences of homologues within each clade, but did not homogenize the coding sequences. Our results suggest that the R1 homologues represent three independent groups of fast‐evolving type I resistance genes, characterized by chimeric structures resulting from frequent sequence exchanges among group members. Such genes were first identified among clustered RGC2 genes in lettuce, where they were distinguished from slow‐evolving type II R‐genes. Our findings at the R1 locus in S. demissum may indicate that a common or similar mechanism underlies the previously reported differentiation of type I and type II R‐genes and the differentiation of type I R‐genes into distinct groups, identified here.
Evaluation of non‐specific effects of infant immunizations on early infant mortality in a southern Indian population
Authors: Moulton Lawrence H. , Rahmathullah Lakshmi , Halsey Neal A. , Thulasiraj R. D. , Katz Joanne , Tielsch James M.
Published: September 2005

Objective  The aim of this study was to assess the relationship between receipt of routine childhood immunizations and infant mortality before 6 months of age.

Methods  This was an observational study of 10 274 infants, in a randomized trial of vitamin A supplementation, who received the study dose and survived to at least 1 week of age. The primary outcome was mortality before 6 months of age, analysed in Cox regression models as a function of vaccine receipt and gender.

Results  Receipt of Bacille Calmette Guerin (BCG) or diphtheria, tetanus, polio (DTP) vaccine was associated with significant reductions of one‐half to two‐thirds of mortality hazards; among girls, those who received both BCG and DTP experienced higher mortality than those who received only one of the two vaccines (hazards ratio 2.4; 95% confidence interval 1.2–5.0).

Conclusion  The reduced mortality rate associated with receipt of BCG or DTP may be due to both biological and selection factors; the analyses regarding the combined effect of these vaccines and gender need to be replicated in other settings.
Orobanche crenata resistance and avoidance in pea (Pisum spp.) operate at different developmental stages of the parasite
Authors: PÉREZ‐DE‐LUQUE A , JORRÍN J , CUBERO J I , RUBIALES D
Published: September 2005

Orobanche crenata (broomrape) is an important constraint to pea (Pisum sativum) cultivation in the Mediterranean area, because little resistance is available in commercial crop varieties. Field experiments have demonstrated that some resistance is present in a number of P. sativum and P. fulvum accessions. The goal of this work was to characterize such resistance. The Pisum–O. crenata interaction and the resistance symptoms were studied under controlled conditions by using Petri dish and polyethylene bag assays. The content of phenolics and peroxidase activity in host tissue from infected and non‐infected plants were also measured. Resistance and avoidance mechanisms, acting at different developmental stages of the parasite, have been identified, including low stimulation of O. crenata seed germination, unsuccessful penetration of host roots, delay in post‐attachment tubercle development and necrosis of the attached tubercles. Infection caused an increase in the content of total soluble phenolics in some Pisum genotypes. Peroxidase activity was higher in resistant than in susceptible accessions. Results obtained with different Pisum genotypes showed that resistance is the result of several mechanisms acting at different stages of the infection process. Resistance is also related to increased levels of peroxidase activity in host roots.
Quality versus quantity: spring wheat seed size and seeding rate effects on Avena fatua interference, economic returns and economic thresholds
Authors: STOUGAARD R N , XUE Q
Published: September 2005

A 3‐year field experiment was conducted at Kalispell, Montana, USA, to investigate the effects of spring wheat seed size and seeding rate on wheat yield loss (YL), economic returns and economic thresholds (ETs), as a function of Avena fatua density. Crop competitive ability increased as wheat seeding rate and seed size increased, with the greatest differences among treatment factors being observed at low weed densities. Both treatment factors decreased spring wheat YL, increasing economic returns during all 3 years of the study despite the higher associated seed costs. Averaged over all other factors, adjusted gross returns (AGR) were 477 and 537$ ha−1 for the low and high seeding rates, while values of 453, 521 and 547$ ha−1 were obtained for the small, bulk and large seed size classes respectively. Weed‐free yield potential varied yearly. As yield potential increased, A. fatua competitive effects were more evident and ETs decreased. Nonetheless, both treatment factors increased ETs in 2 of 3 years. These results demonstrate that the use of higher seeding rates and larger seed size classes both improve wheat competitive ability towards A. fatua while simultaneously increasing economic returns.
Germination characteristics of Amaranthus quitensis as affected by seed production date and duration of burial
Authors: FACCINI D , VITTA J I
Published: September 2005

Thermal requirements for the germination of Amaranthus quitensis, a common annual weed in Argentina, were studied. In addition, temporal changes in dormancy from seeds produced at different times during the growing season were examined. For this second objective, thermal and light requirements for germination were tested in seeds buried at different depths, with or without crop residues. Base and optimum temperatures for germination rates were 12.8°C and 37°C respectively. At dispersal time, maximum percentage germination was 60–70% and this was generally recorded at 35°C/25°C in a 14‐h photoperiod. Seed germination tended to increase in later seed collection dates. Seeds of A. quitensis showed seasonal changes in germinability in the soil. In winter, germination of retrieved seeds increased to over 90% until summer, after which there was a decrease until the following winter when germination was close to 40%. There were no differences in germinability between burial depths and crop residue levels. Germination requirements for alternating temperatures and light tended to disappear after burial. Initial viability was 99% and declined slightly during burial. Soil temperature seems to play a crucial role not only by regulating seasonal changes in dormancy, but also by defining the percentage and the germination rate in non‐dormant seeds.
Pancreatico‐renal composite transplant: a new technique designed to decrease pancreatic graft thrombosis
Authors: Dafoe Donald C , Ratner Lloyd E
Published: September 2005

Abstract: Pancreas graft thrombosis continues to be a major cause of graft loss. The removal of the donor spleen is accompanied by a significant reduction in pancreas graft blood flow. It is likely that reduced blood flow contributes to thrombosis in concert with other factors. We present a case of simultaneous pancreas and dual kidney transplantation wherein one donor kidney was anastomosed to the splenic vessels of the pancreas graft. The portal venous drainage of the pancreas graft was into the vena cava and duodenal segment was drained into the recipient's jejunum. Intraoperative blood flow determinations using an ultrasonic flow probe around the graft portal vein showed that the placement of the renal graft in the position of the donor spleen improved flow by approximately one‐third (e.g. at 15 min after transplantation, 800 cc/min vs. 550 cc/min with the composite vascular pedicle clamped). The perfusion phase of a radionuclide scan on postoperative day 3 showed both transplanted kidneys had brisk and comparable visualization. The patient had an uneventful recovery and was discharged on the seventh postoperative day with normal blood glucose values and a serum creatinine of 1.2 mg/mL. A pancreatico‐renal composite graft may decrease the incidence of thrombosis by improving pancreatic graft blood flow.
Surgical considerations in the correction of valve dysfunction following heart transplantation
Authors: Kpodonu Jacques , Massad Malek G , Geha Alexander S
Published: September 2005

Abstract:  Valve dysfunction is not an uncommon occurrence following heart transplantation but when present can be managed medically with diuretics and vasodilator therapy. If medical therapy fails, these patients are considered for retransplantation. Due to the scarcity of donor hearts, efforts aimed at limiting the pool of cardiac retransplantation candidates are being focused lately on preservation of cardiac allograft function by conventional operations in lieu of a retransplant. A review of the literature for patients who underwent valve operations following their heart transplants yielded 26 cases. Four of these had isolated mitral valve procedures, 18 had tricuspid procedures, two had combined mitral and tricuspid operations and two had aortic valve replacements. In this communication, we present a case of severe aortic insufficiency developing 7 yr after heart transplantation and leading to progressive clinical deterioration and NYHA class IV heart failure symptoms. The aortic valve was replaced with a 21‐mm Carbo Medics supra‐annular mechanical prosthesis (CarboMedics Inc.). She had a favorable postoperative course and remains well 7 months after her operation. Surgical correction of valvular lesions is warranted if the function of the previously transplanted heart is reasonably preserved.
Could post‐liver transplantation course be helpful for the diagnosis of so called cryptogenic cirrhosis?
Authors: Duclos‐Vallée Jean‐Charles , Yilmaz Funda , Johanet Catherine , Roque‐Afonso Anne‐Marie , Gigou Michelle , Trichet Catherine , Féray Cyrille , Ballot Eric , Dussaix Elisabeth , Castaing Denis , Bismuth Henri , Samuel Didier , Guettier Catherine
Published: September 2005

Abstract:  Cryptogenic cirrhosis (CC) is diagnosed in 5–30% of cirrhotic patients overall and 7% of patients who undergo liver transplantation for cirrhosis. In our series of patients transplanted for CC, pre‐transplant clinical and histological data and the post‐transplant course were reexamined in an attempt to identify the aetiology. Among the 881 patients transplanted in our centre between 1987 and 2000, 28 patients with a median age of 46 yr (range: 18–69) at transplantation were initially classified as having CC. Two patients were excluded because of intense ischaemic lesions caused by chemoembolization prevented histological analysis of the native liver (n = 1) and because of cryptic HBV infection (n = 1). Among the remaining 26 patients, four groups were individualized: (i) patients with chronic inflammatory liver disease with autoimmune features (n = 14, 54%); (ii) patients with features suggestive of non‐alcoholic fatty liver disease (n = 3, 11.5%); (iii); patients with incomplete septal cirrhosis (ISC) and vascular liver disease (n = 3), and (iv) patients with unresolved CC (n = 6, 23%). In the autoimmune liver disease group, the median International Autoimmune Hepatitis score was 12.5 (range: 11–19) after reevaluation and review of the post‐transplantation course was helpful to confirm the diagnosis with the occurrence of active graft hepatitis in nine patients, with autoantibodies in five patients. The vascular group was characterized by lesions of obliterative portal venopathy and ISC in all native livers. Diagnosis of NAFLD was based on the clinical background of obesity and/or type 2 diabetes and the presence of steatosis or steatohepatitis in native livers and graft biopsies. A definite aetiological diagnosis can be achieved in the majority of patients initially diagnosed with CC. Autoimmune liver disease emerged as the main aetiology (14 of 26 patients, 54%) and frequently recurred on the grafted liver (nine cases). In all cases a precise diagnosis is obviously of practical interest for better management of post‐transplant survey and treatment.