bluuebunny/crossref_metadata_2025 huggingface dataset:
Cucumber mosaic virus-encoded 2b suppressor inhibits Arabidopsis Argonaute1 cleavage activity to counter plant defense
Authors: Zhang Xiuren , Yuan Yu-Ren , Pei Yi , Lin Shih-Shun , Tuschl Thomas , Patel Dinshaw J. , Chua Nam-Hai
Published: December 2006

RNA silencing refers to small regulatory RNA-mediated processes that repress endogenous gene expression and defend hosts from offending viruses. As an anti-host defense mechanism, viruses encode suppressors that can block RNA silencing pathways. Cucumber mosaic virus (CMV)-encoded 2b protein was among the first suppressors identified that could inhibit post-transcriptional gene silencing (PTGS), but with little or no effect on miRNA functions. The mechanisms underlying 2b suppression of RNA silencing are unknown. Here, we demonstrate that the CMV 2b protein also interferes with miRNA pathways, eliciting developmental anomalies partially phenocopying ago1 mutant alleles. In contrast to most characterized suppressors, 2b directly interacts with Argonaute1 (AGO1) in vitro and in vivo, and this interaction occurs primarily on one surface of the PAZ-containing module and part of the PIWI-box of AGO1. Consistent with this interaction, 2b specifically inhibits AGO1 cleavage activity in RISC reconstitution assays. In addition, AGO1 recruits virus-derived small interfering RNAs (siRNAs) in vivo, suggesting that AGO1 is a major factor in defense against CMV infection. We conclude that 2b blocks AGO1 cleavage activity to inhibit miRNA pathways, attenuate RNA silencing, and counter host defense. These findings provide insight on the molecular arms race between host antiviral RNA silencing and virus counterdefense.
Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans
Authors: Tanizawa Yoshinori , Kuhara Atsushi , Inada Hitoshi , Kodama Eiji , Mizuno Takafumi , Mori Ikue
Published: December 2006

Although recent studies have provided significant molecular insights into the establishment of neuronal polarity in vitro, evidence is lacking on the corresponding phenomena in vivo, including correct localization of synaptic components and the importance of this process for function of the nervous system as a whole. RIA interneurons act as a pivotal component of the neural circuit for thermotaxis behavior in the nematode Caenorhabditis elegans and provide a suitable model to investigate these issues, having a neurite clearly divided into pre- and post-synaptic regions. In a screen for thermotaxis mutants, we identified the gene ttx-7, which encodes myo-inositol monophosphatase (IMPase), an inositol-producing enzyme regarded as a bipolar disorder-relevant molecule for its lithium sensitivity. Here we show that mutations in ttx-7 cause defects in thermotaxis behavior and localization of synaptic proteins in RIA neurons in vivo. Both behavioral and localization defects in ttx-7 mutants were rescued by expression of IMPase in adults and by inositol application, and the same defects were mimicked by lithium treatment in wild-type animals. These results suggest that IMPase is required in central interneurons of the mature nervous system for correct localization of synaptic components and thus for normal behavior.
Difference in blood and water diffusion distance in gill lamellae of diploid and triploid tench Tinca tinca (L.)
Authors: Flajšhans M. , Piačková V.
Published: December 2006

Image analysis of sagittal sections of gill lamellae of diploid and triploid tench Tinca tinca revealed the blood and water diffusion distance in diploids (2·07 μm) to be significantly higher than that of their triploid siblings (1·46 μm; P < 0·01). Lamellae of diploids compared to triploids were found to be significantly shorter (105·84 v. 132·11 μm) and thicker (18·47 v. 14·21 μm; all at P < 0·05) than those of their triploid siblings but with similar mean sectional areas (1965·44 v. 1910·86 μm2).
The importance of mangroves, mud and sand flats, and seagrass beds as feeding areas for juvenile fishes in Chwaka Bay, Zanzibar: gut content and stable isotope analyses
Authors: Lugendo B. R. , Nagelkerken I. , Van Der Velde G. , Mgaya Y. D.
Published: December 2006

The relative importance of bay habitats, consisting of mangrove creeks and channel, seagrass beds, and mud and sand flats, as feeding grounds for a number of fish species was studied in Chwaka Bay, Zanzibar, Tanzania, using gut content analysis and stable isotope analysis of carbon and nitrogen. Gut content analysis revealed that within fish species almost the same food items were consumed regardless of the different habitats in which they were caught. Crustaceans (mainly copepods, crabs and shrimps) were the preferred food for most zoobenthivores and omnivores, while fishes and algae were the preferred food for piscivores and herbivores, respectively. The mean δ13C values of fishes and food items from the mangrove habitats were significantly depleted to those from the seagrass habitats by 6·9 and 9·7‰ for fishes and food items, respectively, and to those from the mud and sand flats by 3·5 and 5·8‰, respectively. Fishes and food items from the mud and sand flats were significantly depleted as compared to those of the seagrass habitats by 3·4 and 3·9‰, for fishes and food, respectively. Similar to other studies done in different geographical locations, the importance of mangrove and seagrass themselves as a primary source of carbon to higher trophic levels is limited. The different bay habitats were all used as feeding grounds by different fish species. Individuals of the species Gerres filamentosus, Gerres oyena, Lethrinus lentjan, Lutjanus fulviflamma, Pelates quadrilineatus and Siganus sutor appeared to show a connectivity with respect to feeding between different habitats by having δ13C values which were in‐between those of food items from two neighbouring habitats. This connectivity could be a result of either daily tidal migrations or recent ontogenetic migration.
Stable isotope analyses of collagen in fish scales: limitations set by scale architecture
Authors: Hutchinson J. J. , Trueman C. N.
Published: December 2006

Comparisons between the stable isotope composition of carbon in collagen excized from juvenile (freshwater) and adult (marine) portions of scales from Atlantic salmon Salmo salar demonstrated that c. 75% of carbon analysed in the ‘juvenile’ portion of the scale derives from later formed collagen. Scale collagen analyses were effectively restricted to the last season of growth.
Effects of river flow on larval growth and survival of Japanese seaperch Lateolabrax japonicus (Pisces) in the Chikugo River estuary, upper Ariake Bay
Authors: Shoji J. , Ohta T. , Tanaka M.
Published: December 2006

The abundance and growth history of larval and juvenile Japanese seaperch Lateolabrax japonicus were investigated in the Chikugo River estuary, upper Ariake Bay, from 1990 to 2000. Growth during the larval period (up to 15 mm standard length, LS, the size at recruitment into the estuary) was backcalculated using sagittal otolith microstructures by the biological intercept method. Growth rates in length declined at body sizes >14 mm LS. High freshwater discharge through the Chikugo River was associated with high temperatures of the upper Ariake Bay where the larvae spend their planktonic life. Mean larval stage duration (days) from hatch to 15 mm (D15) varied between 48·8 and 76·2 days and was inversely correlated with the estimated mean temperature history [mean daily temperature (° C) experienced by the larvae during the period from hatch to 15 mm, T15]. Mean abundance (number m−2) of larvae and juveniles was highest in years when T15, D15 and freshwater discharge were at intermediate levels. Although the abundance was not correlated with either of these variables, an exponential relationship between abundance and D15 was found when data collected during the highest river discharge years (1990, 1991 and 1998) were excluded. The increase in freshwater discharge through the Chikugo River probably had the potential to enhance or diminish Japanese seaperch recruitment in two ways: 1) it could increase recruitment probability by increasing temperature and larval growth and 2) high river flow also had the potential to decrease the probability of immigration into the river by increasing larval seaward dispersion, predation due to decreased turbidity and starvation due to decreased zooplankton prey abundance in the estuary.
Spawning sounds in meagre Argyrosomus regius recorded in the Gironde estuary, France
Authors: Lagardère J. P. , Mariani A.
Published: December 2006

During their spawning period (June to mid‐July) in the Gironde estuary, meagre Argyrosomus regius produce two distinct sounds: regular long grunts, the most common calls, and sometimes also short grunts. It is suggested that long grunts serve the formation of spawning aggregations and short grunts announce the beginning of courtship behaviour. The meagre’s long grunts include long series of 30–112 closely spaced pulses placed into call units. Each pulse produces multiple and rapidly decaying swimbladder vibrations with a dominant frequency varying between 336 and 444 Hz.
Morphological abnormalities in a blue shark Prionace glauca (Chondrichthyes: Carcharhinidae) foetus from southern Brazil
Authors: Mancini P. L. , Casas A. L. , Amorim A. F.
Published: December 2006

This study records the occurrence of a blue shark Prionace glauca foetus, with morphological abnormalities in the trunk and cephalic region, from a female caught by a pelagic longline in October 2003, in southern Brazil.
Evidence of a novel reproductive tactic in female kokanee Oncorhynchus nerka
Authors: Morbey Y. E. , Guglielmo C. G.
Published: December 2006

Body composition analysis confirmed that egg development and reproductive senescence were delayed in silver female kokanee Oncorhynchus nerka (a small proportion of female kokanee exhibit extreme prespawning waiting and are called ‘silvers’ because of their colouration) relative to that of red female kokanee (most female kokanee exhibit this ‘normal’ phenology and are called ‘reds’). Silver females were also smaller and younger than red females. A simple life‐history model with two size thresholds is proposed to account for the observed body size and age differences. Adoption of the silver tactic by small females is proposed as a means to minimize intrasexual competition.
Evidence for sexual dichromatisms in spawning aggregations of yellowfin grouper Mycteroperca venenosa and tiger grouper Mycteroperca tigris from the southern Gulf of Mexico
Authors: Tuz‐Sulub A. , Brulé T. , Cervera‐Cervera K. , Espinoza‐Mendez J. C.
Published: December 2006

Colour pattern characteristics and gonad histology were used to detect sexual dichromatisms in yellowfin grouper Mycteroperca venenosa and tiger grouper Mycteroperca tigris from the Campeche Bank, Mexico. Specimens were obtained from commercial catches between March and May during 2002 and 2004. All specimens were examined dead. Ninety‐seven per cent of males had different sex‐associated colour patterns. Male yellowfin grouper displayed a bright yellow blotch on both sides of the lower jaw while females retained a reddish lower jaw. Male tiger grouper had uniform dark pectoral fins while females had bright orange pectoral fins. In situ observations of live fishes at fishing sites showed the lower jaw and pectoral fin colourations to be clearly visible underwater at a depth of 35 m. All males of both species and most females (80% yellowfin grouper and 98% tiger grouper) were sexually active and probably caught during their spawning season. This suggests that distinct colourations observed for male M. venenosa and M. tigris may be seasonal displays associated with spawning. Both the lower jaw and pectoral fin colourations were still visible in dead fishes after several days on ice. Differences observed for ray length of exserted vertical fins in tiger grouper specimens were probably not a sex‐associated characteristic.
The effects of chronic developmental hypoxia on swimming performance in zebrafish
Authors: Widmer S. , Moore F. B.‐G. , Bagatto B.
Published: December 2006

Relative to normoxia‐reared fish, hypoxia‐reared zebrafishDanio rerioachieved 24·9 and 21·4% slower maximal swim velocities in both normoxic and hypoxic waters, respectively. Hypoxia‐reared fish also produced 26·1 and 63·9% less lactate during resting conditions across both normoxic and hypoxic waters, respectively. During exercise, this trend continued as hypoxia‐reared fish produced 68·2 and 55·1% less lactate across both normoxic and hypoxic waters, respectively. This reduction in performance, rather than representing a purely pathological (maladaptive) response to hypoxia, appears to represent a fundamental shift in the metabolic response to hypoxia.
Ontogenetic allometric coefficient changes: implications of diet shift and morphometric traits in Hoplias malabaricus (Bloch) (Characiforme, Erythrinidae)
Authors: Teixeirade Mello F. , Iglesias C. , Borthagaray A. I. , Mazzeo N. , Vilches J. , Larrea D. , Ballabio R.
Published: December 2006

This study evaluated the relationship between body size and digestive tract characteristics of the important predatory freshwater fish Hoplias malabaricus, which is widely distributed in South America. The allometric coefficients were calculated for the mass and standard length (LS) relationships for two different LS groups: (1) between 20 and 100 mm (characterized as insectivores) and (2) >100 mm (characterized as piscivores). Differential growth measured from the allometric coefficient, b, between the insectivore (b < 3) and the piscivore (b > 3) groups was detected. Anterior intestine length and pyloric caeca zone length showed significant differences between groups. Two complementary hypotheses were developed to explain the differential growth: (1) H. malabaricus has a digestive tract adapted to a piscivorous diet, which is independent of its ontogenetic stage of development, and (2) the negative allometry observed in group 1 individuals agrees with a general behavioural strategy, allowing individuals to grow in LS during a shorter period of time.
Models of the turning and fast‐start swimming dynamics of aquatic vertebrates
Authors: Blake R. W. , Chan K. H. S.
Published: December 2006

Two models for unpowered and powered turns and C‐type fast‐starts were developed and applied to four different manoeuvres: unpowered turns by a streamlined fish (yellowfin tuna Thunnus albacares), powered turns by an unstreamlined fish (boxfish Ostracion meleagris), fast‐starts (sticklebacks Gasterosteus spp.) and a manoeuvre by a steller sea lion Eumetopias jubatus deploying control surfaces (flippers). The velocity at the end of manoeuvres (terminal velocity) was employed as the ‘benchmark variable’ for comparisons of predicted and actual performance. Good agreement was found in all cases. A log–log plot of available experimental data for turning radius v. mass shows that turning radius scales to the 0·37 power of mass (r2= 0·73), close to the predicted value of 0·33. Recent interests in highly manoeuvrable aquatic vertebrates as biomimetic models for automated underwater vehicles adds to the practical utility of the models presented here.
Breeding cycles and reproductive behaviour in the river blenny Salaria fluviatilis
Authors: Lengkeek W. , Didderen K.
Published: December 2006

Female gravidity (assessed according to the roundness of the female’s abdomen) in a population of Corsican river blennies Salaria fluviatilis showed a cyclical pattern over the breeding season. Behavioural interactions between males and females matched these cycles. The rate of female visits to males’ territories did not differ between periods of high and low daily average gravidity in the population. While males courted a similar proportion of females in both periods, they rejected a higher proportion of females when daily average gravidity was high. Furthermore female courtship of males was observed at this time, whereas it never occurred during low daily average gravidity periods. Thus, temporal variation in female availability for spawning caused both males and females to alter their behaviour in such a way that a sex role reversal in courtship was observed.
The recombinant kringle domain of urokinase plasminogen activator inhibits in vivo malignant glioma growth
Authors: Kim Chung Kwon , Hong Sung Hee , Ae Joe Young , Shim Byoung‐Shik , Lee Suk‐Keun , Hong Yong‐Kil
Published: December 2006

In a previous report, the recombinant kringle domain (UK1) of the urokinase type plasminogen activator (uPA) showed antiangiogenic activity. Here, we investigated in vivo antitumor effects of the UK1 of human uPA employing a brain tumor model. The systemic administration of UK1 purified from pichia expression (10 and 50 mg/kg/day intraperitoneally for 25 days) led to suppress the growth of a U87 human glioma xenograft, implanted into the brains of male BALB/cSlc nude mice, by 35% and 80%, respectively. In the immunohistochemical analysis, the tumors treated with UK1 showed decreased vascularity and expression of angiogenesis‐related factors including vascular endothelial growth factor (VEGF), angiogenin, α‐smooth muscle actin, von Willebrand's factor, and CD31 (PECAM‐1 [Platelet endothelial cell adhesion molecule‐1]), and increased apoptosis. UKl inhibited the in vitro proliferation and tube formation of VEGF‐stimulated endothelial cells but not the proliferation of glioma cells. These results suggest that UK1 inhibits the malignant glioma growth by suppression of angiogenesis. (Cancer Sci 2007; 98: 253–258)
β1 integrin mediated adhesion increases Bim protein degradation and contributes to drug resistance in leukaemia cells
Authors: Hazlehurst L. A. , Argilagos R. F. , Dalton W.S.
Published: December 2006

It has been shown that the tumour microenvironment confers resistance to chemotherapy. Specifically, it was previously reported that adhesion of haematopoietic tumour cells to fibronectin (FN) via β1 integrins confers a multi‐drug resistance phenotype commonly referred to as cell adhesion mediated drug resistance. The present study showed that the pro‐apoptotic BCL‐2 family member Bim was reduced when leukaemia cells were adherent to FN via β1 integrins. β1 integrin‐mediated regulation of Bim in K562 cells was demonstrated to be partly a result of increased proteasomal‐mediated degradation of Bim protein levels, and proteasome inhibitors prevent Bim degradation. Increased degradation of Bim was not related to activation of the mitogen‐activated protein kinase pathway, as adhesion of K562 cells caused a reduction in phospho‐extracellular signal‐related kinase (ERK)1/2 levels. In addition, pharmacological inhibition of MAP/ERK (MEK) with PD98059 did not increase Bim levels. Reducing Bim levels by short hairpin RNA targeting inhibited imatinib and mitoxantrone‐induced cell death. These results showed that β1 integrin‐mediated adhesion regulates Bim degradation and may contribute to the minimal residual disease associated with many haematopoietic malignancies. Together our data indicate that disrupting β1 integrin‐mediated regulation of Bim degradation may increase the efficacy of drugs, including imatinib, used to treat haematopoietic malignancies.
Outcomes of patients with haematological malignancies admitted to intensive care unit. A comparative review of allogeneic haematopoietic stem cell transplantation data
Authors: Lim ZiYi , Pagliuca Antonio , Simpson Sylwia , Cottam Simon , Ervine Max , Ho Aloysius Y. L. , Devereux Stephen , Mufti Ghulam J.
Published: December 2006

The outcomes of 55 consecutive haemato‐oncology patients admitted to the intensive care unit (ICU) were retrospectively analysed. Twenty‐eight patients were admitted following haemopoietic stem cell transplantation (HSCT). Thirty‐nine patients were admitted with respiratory failure, and all patients required respiratory support. Seventeen patients survived to be discharged from ICU, with an actuarial 1‐year survival of 18%. Overall survival between patients who received intensive chemotherapy and those who underwent allogeneic HSCT was not significantly different (19% vs. 10%, P = 0·19). None of the nine myeloablative HSCT recipients survived (median survival: 9 d). Six of the 15 reduced‐intensity conditioned HSCT recipients survived beyond 1 year (median survival: 1050 d, range: 438–1437).
Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease
Authors: Pineda‐Roman Mauricio , Bolejack Vanessa , Arzoumanian Varant , Anaissie Elias , Van Rhee Frits , Zangari Maurizio , Walker Ron , Hollmig Klaus , Shaughnessy John D. , Epstein Joshua , Krishna Somashekar , Crowley John , Barlogie Bart
Published: December 2006

Complete response (CR) is still considered an important surrogate marker for outcome in multiple myeloma (MM). Long‐term survival after transplantation, however, has been observed in a substantial proportion of patients who never achieved CR. The tandem transplant trial, Total Therapy 2, enrolled 668 patients, who were randomised up‐front to thalidomide (THAL) or no THAL; 56 patients were identified as having had, for at least 6 months prior to initiation of therapy, monoclonal gammopathy of undetermined significance (MGUS,n = 21), smouldering MM (SMM,n = 22) or solitary plasmacytoma of bone (SPC,n = 13). The clinical characteristics and outcomes of patients with such ‘evolved’ MM (E‐MM) and of those with ‘unknown’ prior history (U‐MM) were compared. Fewer patients with MGUS/SMM‐E‐MM had anaemia or renal failure; CR was lower (22% vs. 48%) but 4‐year estimates of event‐free survival (54% vs. 56% with U‐MM) and overall survival (65% vs. 70% with U‐MM) were similar to those with SPC‐E‐MM or U‐MM. In the latter group, achieving CR was associated with prolonged survival. In comparison with U‐MM, E‐MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting survival. In contrast, CR was an independent favourable feature for survival in U‐MM.
Wnt3A activates canonical Wnt signalling in acute lymphoblastic leukaemia (ALL) cells and inhibits the proliferation of B‐ALL cell lines
Authors: Nygren Marit Kveine , Døsen Guri , Hystad Marit E. , Stubberud Heidi , Funderud Steinar , Rian Edith
Published: December 2006

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Recently, there has been a growing interest in Wnt signalling in several aspects of cellular development, including cancer formation. Little is known about Wnt signalling in B‐ALL. We investigated whether activation of canonical Wnt signalling could occur in B‐ALL cells and thereby play a potential role in cellular growth and/or survival. This study found that Wnt3A induced β‐catenin accumulation in both primary B‐ALL cells and B‐ALL leukaemia cell lines. Further, Wnt3A was shown to induce nuclear translocation of β‐catenin and TCF/Lef‐1 dependent transcriptions in the B‐ALL cell line Nalm‐6. Examination of the mRNA expression pattern of WNT ligands, FZD receptors and WNT antagonists in Nalm‐6 cells identified a set of ligands and receptors available for signalling, as well as antagonists potentially available for modulating the response. Functional analyses showed that Wnt3A inhibited the proliferation of several, but not all, B‐ALL cell lines studied. Finally, microarray analysis was used to identify several Wnt3A target genes involved in a diverse range of cellular activities, which are potential mediators of the Wnt3A‐restrained proliferation.
Non‐opsonising aggregates of IgG and complement in haemoglobin C erythrocytes
Authors: Brittain Nathaniel J. , Erexson Cindy , Faucette Lawrence , Ward Jerrold , Fujioka Hisashi , Wellems Thomas E. , Fairhurst Rick M.
Published: December 2006

Haemoglobin C (HbC) differs from normal HbA by a lysine for glutamate substitution at position 6 of beta‐globin. Heterozygous AC and homozygous CC phenotypes are associated with shortened erythrocyte life spans and mild anaemia. AC and CC erythrocytes contain elevated amounts of membrane‐associated haemichromes, band 3 clusters, and immunoglobulin G (IgG) in vivo. These findings led us to investigate whether AC and CC erythrocytes might expose elevated levels of IgG and complement, two opsonins that have been implicated in the phagocytic clearance of senescent and sickle erythrocytes. Surprisingly, we found IgG, complement, and other plasma proteins co‐localised in aggregates beneath the membrane of circulating AC and CC erythrocytes. These observations, and our finding of similar aggregates in erythrocytes heterozygous or homozygous for haemoglobin S (sickle‐cell haemoglobin), suggest that the vast majority of membrane‐associated IgG and complement detected in these abnormal erythrocytes is intracellular and does not contribute to the eventual opsonic clearance of these cells. Phagocytosis studies with macrophages provide evidence in support of this suggestion. Studies of erythrocyte clearance that involve the detection of membrane‐associated IgG and complement as putative opsonins should investigate the possibility that these plasma proteins reside in the erythrocyte interior, and not on the cell surface.
Different clinical phenotype in triplets with haemophilia A
Authors: BARNES C. , BLANCHETTE V. , LILLICRAP D. , MANN K. , STAIN A. M. , LEGGO J. , HILLIARD P. , CARCAO M.
Published: December 2006

Summary.   Although many patients with haemophilia may have exactly the same residual clotting factor level, the clinical disease phenotype may vary greatly. This variation may be related to different genetic mutations responsible for haemophilia, environmental influences and co‐inheritance of polymorphisms affecting the coagulation system. The study of siblings with haemophilia offers the opportunity to examine additional factors, other than genetic mutation and environment that may impact on the clinical phenotype of haemophilia. We present the unusual case of haemophilia occurring in fraternal triplets. Each of the triplets had a slightly different pattern of bleeding and response to treatment.
Haemoperitoneum associated with ovulation in women with bleeding disorders: the case for conservative management and the role of the contraceptive pill
Authors: PAYNE J. H. , MACLEAN R. M. , HAMPTON K. K. , BAXTER A. J. , MAKRIS M.
Published: December 2006

Summary.  Haemoperitoneum secondary to ruptured corpus luteum is a rare complication for women on anticoagulants and with certain congenital bleeding disorders. A surgical approach is often taken, leading to oophorectomy in many cases. We describe three patients presenting with haemoperitoneum in association with factor VII deficiency, factor X deficiency and sitosterolaemia. In two of the patients, recurrent episodes occurred prior to introduction of the oral contraceptive pill. Conservative management with blood product and factor concentrate support was successful in avoiding surgery in three of the five episodes of bleeding. These cases demonstrate that preservation of ovarian function is possible with a conservative approach and recurrent episodes may be prevented by suppression of ovulation.
Current use of by‐passing agents in Europe in the management of acute bleeds in patients with haemophilia and inhibitors
Authors: ASTERMARK J. , ROCINO A. , VON DEPKA M. , VAN DEN BERG H. M. , GRINGERI A. , MANTOVANI L. G. , MORADO M. , GARRIDO R. P. , SCHIAVONI M. , VILLAR A. , WINDYGA J. ,   THE EHTSB
Published: December 2006

Summary. The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by‐passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 μg kg−1at an interval of 2–4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50–100 IU kg−1every 6–12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life‐threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well‐designed comparative studies to optimize the use of by‐passing agents.
Osteoporosis in haemophilia – an underestimated comorbidity?
Authors: WALLNY T. A. , SCHOLZ D. T. , OLDENBURG J. , NICOLAY C. , EZZIDDIN S. , PENNEKAMP P. H. , STOFFEL‐WAGNER B. , KRAFT C. N.
Published: December 2006

Summary.  A relationship between haemophilia and osteoporosis has been suggested, leading to the initiative for a larger study assessing this issue. Bone mineral density (BMD) was measured by osteodensitometry using dual energy X‐ray absorptiometry (DEXA) in 62 male patients with severe haemophilia A; mean age 41 ± 13.1 years, mean body mass index (BMI) 23.5 ± 3.6 kg m−2. Using the clinical score suggested by the World Federation of Hemophilia, all patients were assessed to determine the severity of their arthropathy. A reduced BMD defined as osteopenia and osteoporosis by World Health Organization criteria was detected in 27/62 (43.5%) and 16/62 (25.8%) patients, respectively. Fifty‐five of sixty‐two (88.7%) patients suffered from haemophilic arthropathy. An increased number of affected joints and/or an increased severity were associated with lower BMD in the neck of femur. Pronounced muscle atrophy and loss of joint movement were also associated with low BMD. Furthermore, hepatitis C, low BMI and age were found to be additional risk factors for reduced BMD in the haemophiliac. Our data shows that in haemophilic patients osteoporosis represents a frequent concomitant observation. The main cause for reduced bone mass in the haemophiliac is most probably the haemophilic arthropathy being typically associated with chronic pain and loss of joint function subsequently leading to inactivity. Further studies including control groups are necessary to elucidate the impact of comorbidities such as hepatitis C or HIV on the development of osteoporosis in the haemophiliac.
Monitoring the genotoxic effects of radiosynovectomy with Re‐186 in paediatric age group undergoing therapy for haemophilic synovitis
Authors: TURKMEN C. , OZTURK S. , UNAL S. N. , ZULFIKAR B. , TASER O. , SANLI Y. , CEFLE K. , KILICOGLU O. , PALANDUZ S. , OZEL S.
Published: December 2006

Summary.  Purpose: The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by Re‐186 in paediatric age group undergoing radiosynovectomy for haemophilic synovitis, by using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessing DNA damage. Methods: Cytogenetic analyses were evaluated in 20 boys (mean age: 13.8 ± 2.7 years) before, and 2 and 90 days after radiosynovectomy from the peripheral lymphocytes of the patients. Joint retention and extra‐articular spread of the radionuclides were evaluated by using quantitative gamma camera imaging. Results: Imaging after radiosynovectomy revealed local lymph node visualization in 8 (40%) patients and hepatosplenic visualization in 3 (15%) patients due to extra‐articular leakage of radioactive material. The mean frequency of chromosome aberrations (0.2 ± 0.4/1000 cells) determined prior to the onset of therapy was not significantly increased in comparison with control values obtained 2 days (0.4 ± 0.5/1000 cells) and 90 days (0.2 ± 0.4/1000 cells) after therapy (P = 0.754 and P = 1.0). In the analysis of MN and SCE, when we compare the baseline levels, the mean MN and SCE frequencies were slightly higher in the control analyses performed 2 and 90 days after radiosynovectomy but there were no significant differences between baseline and control levels (χ2 = 2.621, P = 0.270 and F = 0.573, P = 0.569, respectively). Conclusion: The major finding of this study with relatively small sample is that, radiosynovectomy with Re‐186 does not seem to induce early genotoxic effects on the peripheral blood lymphocytes in paediatric age group.
Definitions for haemophilia prophylaxis and its outcomes: The Canadian Consensus Study
Authors: OTA S. , MCLIMONT M. , CARCAO M. D. , BLANCHETTE V. S. , GRAHAM N. , PARADIS E. , FELDMAN B. M.
Published: December 2006

Summary.  The creation of acceptable standard definitions for terms used in the care and assessment of haemophilia patients has become increasingly important, as a growing number of international clinical studies have been initiated. The Delphi approach has been used in health research to reach consensus in large groups and can be used to develop definitions by using several iterations of surveys eliciting opinions from specialists in the field. Three consecutive surveys were designed based on the Delphi approach and distributed to specialist physicians, nurses and physiotherapists in order to develop definitions for seven haemophilia terms: ‘primary prophylaxis’, ‘secondary prophylaxis’, ‘target joint’, ‘joint bleed’, ‘significant soft‐tissue bleed’, ‘superficial soft‐tissue bleed’ and ‘mucosal bleed’. Suggestions were solicited, compiled into a subsequent survey and fed back to the group to rank‐order the importance of each suggested component of the definition. Final definitions were created using the top‐ranked suggestions and sent back to the experts for approval. Five of the seven terms were highly endorsed with greater than 90% agreement. Some differences in agreement were found when analysed by profession. Haemophilia terms were successfully defined using the Delphi approach. Further refinement from members of the international haemophilia community will ensure that comprehensive standard definitions can be used in multicentre studies in the future.
Enhanced natural killer activity and production of pro‐inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax)
Authors: Castoldi Lindsey , Golim Marjorie Assis , Filho Orlando Garcia Ribeiro , Romagnoli Graziela Gorete , Ibañez Olga Célia Martinez , Kaneno Ramon
Published: December 2006

Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high‐ or low‐acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b+), T‐lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b+ cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3+ CD8+ cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro‐inflammatory cytokines tumour necrosis factor‐α, interleukin‐12p40 and interferon‐γ but not the anti‐inflammatory interleukin‐10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.
Chronic inflammation: a failure of resolution?
Authors: Lawrence Toby , Gilroy Derek W.
Published: December 2006

Inflammation has evolved as a protective response to insult or injury, it's a primordial response that eliminates or neutralises foreign organisms or material, the resolution of inflammation encompasses the endogenous anti‐inflammatory mechanisms that protect us against excessive tissue injury and promote the restoration of tissue structure and function. In fact, our well being and survival depends upon its efficiency and carefully‐balanced control. In general, the innate inflammatory response initiates within minutes and, if all is well, resolves within hours. In contrast, chronic inflammation persists for weeks, months or even years. Here, we are going to discuss the key endogenous checkpoints necessary for mounting an effective yet limited inflammatory response and the crucial biochemical pathways necessary to prevent its persistence.
A systematic review of information in decision aids
Authors: Feldman‐Stewart Deb , Brennenstuhl Sarah , McIssac Kathryn , Austoker Joan , Charvet Agathe , Hewitson Paul , Sepucha Karen R. , Whelan Tim
Published: December 2006

Objective  We completed a systematic review of information reported as included in decision aids (DAs) for adult patients, to determine if it is complete, balanced and accurate.

Search strategy  DAs were identified using the Cochrane Database of DAs and searches of four electronic databases using the terms: ‘decision aid’; shared decision making’ and ‘patients’; ‘multimedia or leaflets or pamphlets or videos and patients and decision making’. Additionally, publications reporting DA development and actual DAs that were reported as publicly available on the Internet were consulted. Publications were included up to May 2006.

Data extraction  Data were extracted on the following variables: external groups consulted in development of the DA, type of study used, categories of information, inclusion of probabilities, use of citation lists and inclusion of patient experiences.

Main results  68 treatment DAs and 30 screening DAs were identified. 17% of treatment DAs and 47% of screening DAs did not report any external consultation and, of those that did, DA producers tended to rely more heavily on medical experts than on patients’ guidance. Content evaluations showed that (i) treatment DAs frequently omit describing the procedure(s) involved in treatment options and (ii) screening DAs frequently focus on false positives but not false negatives. About 1/2 treatment DAs reported probabilities with a greater emphasis on potential benefits than harms. Similarly, screening DAs were more likely to provide false‐positive than false‐negative rates.

Conclusions  The review led us to be concerned about completeness, balance and accuracy of information included in DAs.
African lake management initiatives: The global connection
Authors: Hecky Robert E. , Bootsma Harvey A. , Odada Eric O.
Published: December 2006

There is a global dimension to lake management in Africa and elsewhere that will require a concerted action not only from individual riparian states, but also from regional, continental and global communities. The current global lake threats arise from climate change, regional land degradation and semivolatile contaminants, and share the common feature that the atmosphere is the vector that spreads their impacts over large areas and to many lakes. The Great Lakes of Africa (Malawi, Victoria and Tanganyika) are particularly sensitive to these problems because of their enormous surface areas, slow water flushing rates, and the importance of direct rainfall in their water budgets. Their response times might be slow to yield a detectable change and, unfortunately, their recovery times might also be slow. It is possible for atmospheric effects to act antagonistically to the impacts of catchment change, but antagonistic effects could become synergistic in the future. Improved understanding of the physical dynamics of these lakes, and development of models linking their physical and biogeochemical behaviour to regional, mesoscale climate models, will be necessary to guide lake managers.
Laguna de Bay: Institutional development and change for lake basin management
Authors: Santos‐Borja Adelina , Nepomuceno Dolora N.
Published: December 2006

Laguna de Bay is a large, shallow lake located near Manila, Philippines. The lake is drained by the Pasig River, which flows to Manila Bay. It periodically reverses direction, bringing saline water into this predominately freshwater body. The lake has historically been of great importance to locals who depend on it for fish and related livelihoods. Recently, it also has been considered a source of potable water for the Manila region. The intense land use in the watershed has caused enhanced siltation, and the lake has also been plagued by overfishing, intense aquaculture and water pollution from industrial and domestic sources. This paper overviews these issues and examines the role of the Laguna Lake Development Authority in developing and conserving the lake basin's resources. Two programmes related to fisheries development and an environmental user‐fee programme to control water pollution are critiqued. Lessons learned from the nearly 40 years of experience managing this tropical lake also are presented.
Management challenges of freshwater fisheries in Africa
Authors: Ogutu‐Ohwayo Richard , Balirwa John S.
Published: December 2006

The freshwater fisheries of Africa are important sources of income and protein for the people of the continent, and stocks of biodiversity for the world. This report discusses the experience for eight important lakes (Baringo, Chad, Kariba, Malawi, Naivasha, Nakuru, Tanganyika and Victoria), in order to provide an overview of the challenges facing the African freshwater systems, the interventions undertaken to manage the challenges, the inputs that have been required, and the lessons learned to guide further actions. In particular, the experience of the Global Environment Facility in promoting sustainable fisheries and lake basin management at five of these lakes (Baringo, Chad, Malawi, Tanganyika and Victoria) is discussed. The overall experience to date indicates a lack of effective management actions, as a result of limited accessibility and application of scientific information, poor dissemination of management information, inappropriate and un‐harmonized fishery laws and regulations, inadequate enforcement of existing laws and regulations, weak institutions and institutional processes, and inadequate funds for implementing fishery programmes.
Thrombotic thrombocytopenic purpura in advanced prostate cancer: Case report and published work review
Authors: Caramello Valeria , Dovio Andrea , Caraci Pasquale , Berruti Alfredo , Angeli Alberto
Published: December 2006

Abstract:  Thrombotic thrombocytopenic purpura (TTP) is a generalized disorder of the microcirculation characterized by microangiopathic hemolytic anemia (MHA), thrombocytopenic purpura and systemic microvascular thrombi. TTP has been previously described in two patients with prostate cancer (PC). We report a third case of TTP in a 61‐year‐old man with hormone‐refractory bone metastatic PC. The syndrome presented with confusion, anuric acute renal failure, thrombocytopenia and MHA. A satisfactory recovery was achieved after plasma exchange (PE). TTP should be included in the coagulation disorders occurring in PC patients. Early treatment with plasma exchange is recommended in these particular cases.
Testicular sperm extraction in patients with persistent azoospermia after chemotherapy for testicular germ cell tumor
Authors: Sakamoto Hideo , Oohta Michiya , Inoue Katuki , Fuji Khozo , Fukagai Takashi , Yoshida Hideki
Published: December 2006

Abstract:  Sperm cryopreservation before chemotherapy in young males is recommended because of chemotherapy’s gonadotoxic effects. However, many patients miss sperm banking, and consequently are often sterile. Two azoospermic patients presented to us after chemotherapy, and we obtained sperm from them by testicular sperm extraction (TESE). One patient was 32 years old and had been treated with six cycles of cisplatin, etoposide and bleomycin (BEP) chemotherapy and one cycle of high‐dose chemotherapy for stage III non‐seminoma. Histopathology of the testicular specimen showed germinal aplasia with focal islands of full spermatogenesis. Although two intracytoplasmic sperm injection (ICSI) cycles were performed, pregnancy was not achieved. The other patient was 33 years old who was treated with four cycles of BEP chemotherapy for stage II seminoma. Histopathology of the testicular specimen showed Sertoli‐cell‐only syndrome. Ongoing pregnancy was achieved after one ICSI cycle. TESE should be considered in patients with persistent azoospermia after chemotherapy if frozen sperm samples are not available.
Management of urethral calculi associated with hairballs after urethroplasty for severe hypospadias
Authors: Hayashi Yutaro , Yasui Takahiro , Kojima Yoshiyuki , Maruyama Tetsuji , Tozawa Keiichi , Kohri Kenjiro
Published: December 2006

Abstract:  Urethral calculus is a late complication of urethroplasty for hypospadias when hair‐bearing scrotal skin is included in the neourethra. From 1992 to 2002, we had one adolescent and four adult hypospadiac patients with urethral calculi. All patients had undergone staged repair for severe hypospadias at our institute or another hospital in their childhood. Open ureterolithotomy or endoscopic ureterolithotripsy was conducted except in one patient. Open ureterolithotomy was conducted successfully including retubularization with trimming of the diverticular area of the neourethra in two patients. Endoscopic ureterolithotripsy was conducted via Lithoclast in the other two patients. The calculi were struvite in the four patients.
Corneal injury by wild taro
Authors: Tang Emily WH , Law Ricky WK , Lai Jimmy SM
Published: December 2006

Abstract

We report a case of crystalline keratopathy caused by Alocasia macrorrhiza. The diagnosis was made based on the observation of needle‐like crystals in the corneal stroma following injury to that eye. The condition resolved in 3 months with the disappearance of the crystals confirmed by follow‐up confocal microscopy.
Spontaneous resolution of corneal oedema after inadvertent ‘descemetorhexis’ during cataract surgery
Authors: Pan James C‐H , Eong Kah‐Guan A
Published: December 2006

Abstract

A 96‐year‐old lady underwent cataract surgery complicated by the loss of a 5.5 mm diameter area of Descemet’s membrane (DM) centrally. Postoperatively, severe corneal oedema with folds in the remaining annular ring of DM were observed. The patient was managed conservatively and the corneal oedema gradually resolved over 5 months. Loss of DM can be managed conservatively with good visual outcome without the need for surgical intervention.
Pseudoepitheliomatous hyperplasia mimicking ocular surface squamous neoplasia following cultivated limbal epithelium transplantation
Authors: Fatima Anees , Matalia Himanshu P , Vemuganti Geeta K , Honavar Santosh G , Sangwan Virender S
Published: December 2006

Abstract

A 12‐year‐old girl with total limbal stem cell deficiency in the right eye following chemical burns underwent autologous cultivated limbal epithelium transplantation from the healthy left eye. Postoperatively at 6 weeks a mass at the limbus was noted, which increased in size and involved infero‐nasal limbus extending over 5 mm on bulbar conjunctiva. It was a gelatinous, placoid freely movable mass with irregular surface, multiple intralesional cysts without feeder vessels or intrinsic vascularization and stained brilliantly with rose bengal. Histopathology following excision biopsy showed hyperplastic epithelium with stratified columnar cells and goblet cells. At the last follow‐up, 6 months following cultivated limbal epithelium transplantation the ocular surface was stable without any recurrence of the lesion. We herein report a rare complication of epithelial hyperplasia presenting as leukoplakia following cultivated limbal epithelium transplantation mimicking ocular surface squamous neoplasia.