bluuebunny/crossref_metadata_2025 huggingface dataset:
Deregulation of HEF1 Impairs M-Phase Progression by Disrupting the RhoA Activation Cycle
Authors: Dadke Disha , Jarnik Michael , Pugacheva Elena N. , Singh Mahendra K. , Golemis Erica A.
Published: January 2006

The focal adhesion-associated signaling protein HEF1 undergoes a striking relocalization to the spindle at mitosis, but a function for HEF1 in mitotic signaling has not been demonstrated. We here report that overexpression of HEF1 leads to failure of cells to progress through cytokinesis, whereas depletion of HEF1 by small interfering RNA (siRNA) leads to defects earlier in M phase before cleavage furrow formation. These defects can be explained mechanistically by our determination that HEF1 regulates the activation cycle of RhoA. Inactivation of RhoA has long been known to be required for cytokinesis, whereas it has recently been determined that activation of RhoA at the entry to M phase is required for cellular rounding. We find that increased HEF1 sustains RhoA activation, whereas depleted HEF1 by siRNA reduces RhoA activation. Furthermore, we demonstrate that chemical inhibition of RhoA is sufficient to reverse HEF1-dependent cellular arrest at cytokinesis. Finally, we demonstrate that HEF1 associates with the RhoA-GTP exchange factor ECT2, an orthologue of the Drosophila cytokinetic regulator Pebble, providing a direct means for HEF1 control of RhoA. We conclude that HEF1 is a novel component of the cell division control machinery and that HEF1 activity impacts division as well as cell attachment signaling events.
RAB-10 Is Required for Endocytic Recycling in theCaenorhabditis elegansIntestine
Authors: Chen Carlos Chih-Hsiung , Schweinsberg Peter J. , Vashist Shilpa , Mareiniss Darren P. , Lambie Eric J. , Grant Barth D.
Published: January 2006

The endocytic pathway of eukaryotes is essential for the internalization and trafficking of macromolecules, fluid, membranes, and membrane proteins. One of the most enigmatic aspects of this process is endocytic recycling, the return of macromolecules (often receptors) and fluid from endosomes to the plasma membrane. We have previously shown that the EH-domain protein RME-1 is a critical regulator of endocytic recycling in worms and mammals. Here we identify the RAB-10 protein as a key regulator of endocytic recycling upstream of RME-1 in polarized epithelial cells of the Caenorhabditis elegans intestine. rab-10 null mutant intestinal cells accumulate abnormally abundant RAB-5-positive early endosomes, some of which are enlarged by more than 10-fold. Conversely most RME-1-positive recycling endosomes are lost in rab-10 mutants. The abnormal early endosomes in rab-10 mutants accumulate basolaterally recycling transmembrane cargo molecules and basolaterally recycling fluid, consistent with a block in basolateral transport. These results indicate a role for RAB-10 in basolateral recycling upstream of RME-1. We found that a functional GFP-RAB-10 reporter protein is localized to endosomes and Golgi in wild-type intestinal cells consistent with a direct role for RAB-10 in this transport pathway.
Hsp90 Regulates Activation of Interferon Regulatory Factor 3 and TBK-1 Stabilization in Sendai Virus-infected Cells
Authors: Yang Kai , Shi Hexin , Qi Rong , Sun Shaogang , Tang Yujie , Zhang Bianhong , Wang Chen
Published: January 2006

Interferon regulatory factor 3 (IRF3) plays a crucial role in mediating cellular responses to virus intrusion. The protein kinase TBK1 is a key regulator inducing phosphorylation of IRF3. The regulatory mechanisms during IRF3 activation remain poorly characterized. In the present study, we have identified by yeast two-hybrid approach a specific interaction between IRF3 and chaperone heat-shock protein of 90 kDa (Hsp90). The C-terminal truncation mutant of Hsp90 is a strong dominant-negative inhibitor of IRF3 activation. Knockdown of endogenous Hsp90 by RNA interference attenuates IRF3 activation and its target gene expressions. Alternatively, Hsp90-specific inhibitor geldanamycin (GA) dramatically reduces expression of IRF3-regulated interferon-stimulated genes and abolishes the cytoplasm-to-nucleus translocation and DNA binding activity of IRF3 in Sendai virus-infected cells. Significantly, virus-induced IRF3 phosphorylation is blocked by GA, whereas GA does not affect the protein level of IRF3. In addition, TBK1 is found to be a client protein of Hsp90 in vivo. Treatment of 293 cells with GA interferes with the interaction of TBK1 and Hsp90, resulting in TBK1 destabilization and its subsequent proteasome-mediated degradation. Besides maintaining stability of TBK1, Hsp90 also forms a novel complex with TBK1 and IRF3, which brings TBK1 and IRF3 dynamically into proximity and facilitates signal transduction from TBK1 to IRF3. Our study uncovers an essential role of Hsp90 in the virus-induced activation of IRF3.
TheArabidopsis thaliana PARTING DANCERSGene Encoding a Novel Protein Is Required for Normal Meiotic Homologous Recombination
Authors: Wijeratne Asela J. , Chen Changbin , Zhang Wei , Timofejeva Ljudmilla , Ma Hong
Published: January 2006

Recent studies of meiotic recombination in the budding yeast and the model plant Arabidopsis thaliana indicate that meiotic crossovers (COs) occur through two genetic pathways: the interference-sensitive pathway and the interference-insensitive pathway. However, few genes have been identified in either pathway. Here, we describe the identification of the PARTING DANCERS (PTD) gene, as a gene with an elevated expression level in meiocytes. Analysis of two independently generated transferred DNA insertional lines in PTD showed that the mutants had reduced fertility. Further cytological analysis of male meiosis in the ptd mutants revealed defects in meiosis, including reduced formation of chiasmata, the cytological appearance of COs. The residual chiasmata in the mutants were distributed randomly, indicating that the ptd mutants are defective for CO formation in the interference-sensitive pathway. In addition, transmission electron microscopic analysis of the mutants detected no obvious abnormality of synaptonemal complexes and apparently normal late recombination nodules at the pachytene stage, suggesting that the mutant's defects in bivalent formation were postsynaptic. Comparison to other genes with limited sequence similarity raises the possibility that PTD may present a previously unknown function conserved in divergent eukaryotic organisms.
Actin-based Motility during Endocytosis in Budding Yeast
Authors: Kim Kyoungtae , Galletta Brian J. , Schmidt Kevin O. , Chang Fanny S. , Blumer Kendall J. , Cooper John A.
Published: January 2006

Actin assembly nucleated by Arp2/3 complex has been implicated in the formation and movement of endocytic vesicles. The dendritic nucleation model has been proposed to account for Arp2/3-mediated actin assembly and movement. Here, we explored the model by examining the role of capping protein in vivo, with quantitative tracking analysis of fluorescence markers for different stages of endocytosis in yeast. Capping protein was most important for the initial movement of endocytic vesicles away from the plasma membrane, which presumably corresponds to vesicle scission and release. The next phase of endosome movement away from the plasma membrane was also affected, but less so. The results are consistent with the dendritic nucleation model's prediction of capping protein as important for efficient actin assembly and force production. In contrast, the movement of late-stage endocytic vesicles, traveling through the cytoplasm en route to the vacuole, did not depend on capping protein. The movement of these vesicles was found previously to depend on Lsb6, a WASp interactor, whereas Lsb6 was found here to be dispensable for early endosome movement. Thus, the molecular requirements for Arp2/3-based actin assembly differ in early versus later stages of endocytosis. Finally, acute loss of actin cables led to increased patch motility.
Escaping the Japanese Pyramid: The Association of Small and Medium Sized Enterprise Entrepreneurs (SME Doyukai), 1947–1999
Authors: Ibata-Arens Kathryn , Obayashi Hiromichi
Published: January 2006

In Japanese society the pinnacle of economic and political power resides in Tokyo conglomerates and elite ministries: the Ministry of International Trade and Industry (MITI) and the Ministry of Finance. Until now, the story of this power arrangement has been told from the perspective of national bureaucrats and big business executives. The image projected to the outside world has been of cooperative, trust-based relational contracting with big business at the top “taking care” of its suppliers and subsidiaries below. The story from the bottom, however, is one of technology expropriation (of patentable technology) and monopsony squeeze (unilateral cost-down demands, for example). Firms unwilling to toe the line have been wholly excluded from access to the benefits reserved for those at the top of the pyramid, where one finds lucrative main bank financing, government support, and copious technological information.

This article offers a historical narrative of the political struggle by independent-minded entrepreneurs in postwar Japan. Central to the struggle has been the challenge of building broad-based coalitions to avoid becoming embedded in these hierarchies while at the same time trying to obtain alternative sources of finance and technological know-how. The most successful example of such efforts is the Association of Small and Medium Size Enterprise Entrepreneurs (SME Doyukai). The SME Doyukai has somehow managed to remain completely independent from the state, while most other small business associations have not. This independence has not been free, and the association has gone through a number of institutional dilemmas as a result. We analyze these dilemmas over time and offer comparative lessons.
Estimating Subglottal Pressure using Incomplete Airflow Interruption
Authors: Jiang Jack , Leder Charles , Bichler Allison
Published: January 2006

Objective/Hypothesis: Subglottal pressure (SGP) measurements are often used to assess laryngeal function; however, current methods to measure SGP are invasive or do not estimate SGP during phonation. The purpose of this study was to devise a noninvasive technique to estimate SGP without interrupting phonation.

Study Design: This was a methodologic study designed to calculate the SGP of a human subject.

Methods: A new technique to estimate SGP was developed in which subject airflow was partially interrupted by introducing two different impedances (pneumatic resistors) through a balloon valve controlled mouthpiece. The changes in airflow across varying impedances were used to estimate SGP in human subjects based on the predictable relationships between SGP, impedance, and airflow measurements. The technique was used to assess eight human subjects (age 19–30) phonating at intensities of 65, 72, and 80 dB.

Results: The estimated SGP from the human subjects fell within a range (5.52–8.91 cm H20) that was consistent with previous studies. As other studies have found, SGP estimations significantly increased as subjects phonated at greater intensities (P < .01). Intrasubject standard deviations compared favorably with those from previous studies of complete airflow interruption, suggesting satisfactory reliability. The technique was validated using a mechanical “pseudolung” device (r2 = 0.9982).

Conclusions: Incomplete airflow interruption offers the potential for useful clinical application to assess the severity of vocal pathology by estimating SGP during continuous phonation.
Management of T3N1 Glottic Carcinoma: Therapeutic Outcomes
Authors: Spector J Gershon , Sessions Donald G. , Lenox Jason , Simpson Joseph
Published: January 2006

Objective: The aim of the current study was to determine the best total laryngectomy (TL) approach to the treatment of T3N1 glottic cancer, to study the impact of early nodal disease on stage III glottic cancers, and to describe the preliminary results in a group of patients recently treated for laryngeal preservation (LP).

Methods: A retrospective study of Tumor Research Project data were performed on previously untreated patients with T3N1 glottic squamous cell carcinoma who were treated with curative intent by TL and neck dissection (ND) with or without adjuvant radiation therapy (TL +/− RT) from April 1, 1955 to October 8, 1999 at Washington University School of Medicine/Barnes Jewish Hospital. A preliminary analysis of a similar group of patients more recently treated for LP (1‐1‐2000 to 1‐1‐2005) is reported.

Results: Forty‐two patients with T3N1 glottic carcinoma were treated with TL and ND (TL/ND‐16) and TL with ND and TL (TL/ND/RT‐26). The 5 year observed survival (OS) and disease‐specific survival (DSS) for TL/ND were similar at 62.5%. The 5 year OS and DSS for TL/ND/RT were 53.8% and 58.3%, respectively. There was no survival difference between the two methods. The overall local‐regional control rate was 73.9% (11/42 recurrences). The overall recurrence rate was 38%, with 7.1% recurrence at both the primary site and neck. Recurrence was not related to treatment method. The overall salvage rate (5 year DSS after retreatment) was 20% with 50% salvage for patients with neck recurrence. No patients with local recurrence were survivors. The incidence of second primary cancers was 6.8%. More recently, 26 similar patients were treated with LP techniques. Preliminary results showed a 3 year OS of 63.5% and DSS of 76.8%. Local‐regional control was 85.4%. LP was 88.5%.

Conclusions: The two TL modalities had statistically similar results in terms of survival, recurrence, and complications. Decreased DSS was seen in older patients (>65 years) and in patients with involved resection margins, recurrent disease, and distant metastasis. Patients with T3N1 glottic cancer had an 8% decrease in DSS compared to patients with T3N0 disease. Previously patients with T3N1 disease have been treated with TL resulting in loss of natural voice in all patients. Preliminary results on 26 patients with T3N1 disease, treated between 2000 and 2005 with voice preservation intent, indicate that the OS, DSS, and local‐regional control rates were similar to the TL group, whereas 88.5% of patients maintained natural voice and natural breathing. Use of LP techniques should be the initial therapeutic approach for patients with T3N1 glottic cancer.
A de Novo PABPN1 Germline Mutation in a Patient with Oculopharyngeal Muscular Dystrophy
Authors: Gürtler Nicolas , Plasilova Martina , Podvinec Mihael , Boesch Nemya , Müller Hansjakob , Heinimann Karl
Published: January 2006

Background: Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset autosomal dominantly inherited disorder characterized by dysphagia, ptosis, and proximal limb weakness and is caused by germline mutations (triplet repeat expansions) in the polyadenylate binding protein nuclear 1 (PABPN1) gene.

Objective: To describe a 70‐year‐old female patient with OPMD on the clinical and molecular genetic level and to develop a rapid and efficient molecular genetic screening method to study large patient groups.

Methods: Detailed family history and clinical assessment of the OPMD patient were followed by mutation analysis of the PABPN1 gene by direct DNA sequencing and by our newly developed method, fluorescent PABPN1 polymerase chain reaction (PCR) product (flPPP) method. A cohort of 50 healthy Swiss probands was screened using the flPPP to assess the frequency of the (GCG)7 allele in the Swiss population. Cricopharyngeal myotomy was performed as treatment for dysphagia.

Results: A heterozygous (GCG)9 triplet repeat expansion in PABPN1 was identified. Since the family history proved to be negative, the mutation is likely to have occurred de novo. The frequency of the (GCG)7 allele among healthy Swiss controls amounted to 1%. The flPPP method showed a sensitivity and specificity of 100%. Two years after cricopharyngeal myotomy, the patient is still relieved of dysphagia.

Conclusions: An otolaryngologist should include OPMD in the differential diagnosis of a patient presenting with dysphagia, as this symptom can be the first sign of the disease and family history can be negative. Molecular genetic testing represents a highly accurate and rapid way to confirm the clinical diagnosis of OPMD. Cricopharyngeal myotomy relieves the patient of dysphagia in the majority of cases.
Prognostic Value of Survivin and Livin in Nasopharyngeal Carcinoma
Authors: Xiang Yanqun , Yao Herui , Wang Shusen , Hong Minghuang , He Jiehua , Cao Sumei , Min Huaqing , Song Erwei , Guo Xiang
Published: January 2006

Background and Objectives: Survivin and Livin are new members from the family of anti‐apoptotic factors. Increased levels of Survivin and Livin have been observed in many malignancies and correlated with poor prognosis. Survivin is expressed almost exclusively in proliferating cells, including various kinds of cancers, but Livin expression is relatively rare in cancer cells. Therefore, the present study examines the expressions of Survivin and Livin in nasopharyngeal carcinoma (NPC) and investigates whether their expression contributes to the prognosis of NPC.

Methods: We investigated the expression of Survivin and Livin in 80 NPC samples using immunohistochemistry stain and correlated it with the survival of these patients using log‐rank test and Cox multifactor regression analysis.

Results: All the patients were followed up at least for 60 months. During the following period, 21 cases developed distant metastasis, 9 cases developed local‐regional recurrence, and 5 developed both distant metastasis and local‐regional recurrence. Among them, 30 patients died of recurrence of tumor. In addition, the expression of Survivin was related with distant metastasis. Patients with low Survivin expression had better overall survival, disease‐free survival and distant metastasis‐free survival rates than the group with high Survivin expression (P = .0086, .0097, and .0318, respectively). Cox regression analysis confirmed that high Survivin expression was related to worse prognosis in NPC patients. However Livin expression level was not related with the survival of patients with NPC.

Conclusion: NPC expresses high levels of Survivin and Livin, which may play an important role in the oncogenesis and tumor development. Over‐expression of Survivin was related with poor prognosis. We suggest that the determination of Survivin expression may provide predictive information on NPC patients.
Radiographic Stage Fails to Predict Symptom Outcomes after Endoscopic Sinus Surgery for Chronic Rhinosinusitis
Authors: Bhattacharyya Neil
Published: January 2006

Objective: To determine whether preoperative computed tomography (CT) stage predicts degree of symptom improvement after endoscopic sinus surgery (ESS).

Methods: A series of adult patients undergoing ESS was prospectively evaluated with CT and the rhinosinusitis symptom inventory (RSI) preoperatively and at a minimum of 12 months postoperatively. Symptom domains (nasal, facial, oropharyngeal, systemic, and total) were computed and both absolute change and percentage change in symptom domain scores before and after ESS were correlated with the preoperative CT scan stage according to three staging systems: Lund‐MacKay, Kennedy, and Harvard.

Results: One‐hundred sixty‐one patients (mean age, 40.2 years) completed the study with a mean follow‐up of 19.4 months. Overall, statistically significant decreases in RSI symptom domains were noted for the nasal (net change –30.1 [range –100 to +100]), facial (–26.1), oropharyngeal (–13.4), systemic (–17.0), and total (–20.8) symptom scores (all P < .001). For the absolute change in total symptom score, no statistically significant correlation with CT stage was demonstrated for any of the staging systems (Lund: Spearman ρ = −0.004, P = .962; Kennedy: ρ = −0.008, P = .918; Harvard: ρ = −0.011, P= .891). Similarly, no significant correlation with CT stage was demonstrated with the other symptom domains. Additionally, no significant correlation was identified between preoperative CT stage and percentage change in symptom domain scores.

Conclusions: Although CT scan is widely accepted as an accurate diagnostic tool for chronic rhinosinusitis, CT scan stage alone does not significantly predict symptom outcomes after chronic rhinosinusitis, regardless of staging system utilized.
Reinterpreting the origins of flamingo lice: cospeciation or host-switching?
Authors: Johnson Kevin P , Kennedy Martyn , McCracken Kevin G
Published: January 2006

The similarity of the louse faunas of flamingos and ducks has been used as evidence that these two groups of birds are closely related. However, the realization that ducks actually are more closely related to Galliformes caused many workers to reinterpret this similarity in parasite faunas as host switching from ducks to flamingos. Recent unexpected phylogenetic results on the relationships of waterbirds and their lice call for a reinterpretation of the origins of the lice of the enigmatic flamingos. Here, we bring together new evidence on the phylogenetic relationships of flamingos and their lice and show that the lice of flamingos and grebes are closely related because their hosts share a common ancestor (cospeciation). We also demonstrate that the similarity of the louse faunas of flamingos and ducks is a result of host switching from flamingos to ducks, rather than from ducks to flamingos.
Phase transitions in a slender cylinder composed of an incompressible elastic material. II. Analytical solutions for two boundary-value problems
Authors: Cai Zongxi , Dai Hui-Hui
Published: January 2006

In this sequel paper, we solve two boundary-value problems for the asymptotic model equation derived in the first paper. One of the purposes is to compare the analytical solutions with the experimental results obtained by a number of other authors. With the help of a phase-plane analysis on this model, first we manage to solve a force-controlled problem. We find that it is necessary to divide the external stress into seven intervals. Analytical solutions in all intervals are obtained. An interesting finding is that the value of the radius–length ratio has a great influence on the solutions. In particular, it influences the number of non-trivial solutions. In this regard, the potential application of this result to the cold drawing industry is pointed out. Our results also yield the possible nucleation stress which turns out to be dependent on the radius–length ratio
a
. A simple approximate formula for the nucleation stress is given, which shows that it is a decreasing function of
a
. This seems to capture the size effect observed in experiments: the smaller the diameter is, the larger the nucleation stress is. We also obtain the analytic solutions for a displacement-controlled problem with the help of those of a force-controlled problem. The engineering stress–strain curve plotted from the solution of the preferred configurations seems to capture the key features of the curve measured in a few experiments.
Linking herbivore‐induced defences to population dynamics
Authors: VAN DER STAP IRENE , VOS MATTHIJS , MOOIJ WOLF M.
Published: January 2006

1. Theoretical studies have shown that inducible defences have the potential to affect population stability and persistence in bi‐ and tritrophic food chains. Experimental studies on such effects of prey defence strategies on the dynamics of predator–prey systems are still rare. We performed replicated population dynamics experiments using the herbivorous rotifer Brachionus calyciflorus and four strains of closely related algae that show different defence responses to this herbivore.

2. We observed herbivore populations to fluctuate at a higher frequency when feeding on small undefended algae. During these fluctuations minimum rotifer densities remained sufficiently high to ensure population persistence in all the replicates. The initial growth of rotifer populations in this treatment coincided with a sharp drop in algal density. Such a suppression of algae by herbivores was not observed in the other treatments, where algae were larger due to induced or permanent defences. In these treatments we observed rotifer population densities to first rise and then decline. The herbivore went extinct in all replicates with large permanently defended algae. The frequency of herbivore extinctions was intermediate when algae had inducible defences.

3. A variety of alternative mechanisms could explain differential herbivore persistence in the different defence treatments. Our analysis showed the density and fraction of highly edible algal particles to better explain herbivore persistence and extinctions than total algal density, the fraction of highly inedible food particles or the accumulation of herbivore waste products or autotoxins.

4. We argue that the rotifers require a minimum fraction and density of edible food particles for maintenance and reproduction. We conjecture that induced defences in algae may thus favour larger zooplankton species such as Daphnia spp. that are less sensitive to shifts in their food size spectrum, relative to smaller zooplankton species, such as rotifers and in this way contributes to the structuring of planktonic communities.
Human T‐cell leukemia virus type‐I oncoprotein Tax inhibits Fas‐mediated apoptosis by inducing cellular FLIP through activation of NF‐κB
Authors: Okamoto Kazuo , Fujisawa Jun‐ichi , Reth Michael , Yonehara Shin
Published: January 2006

Human T‐cell leukemia virus type I (HTLV‐I) is an etiologic agent of adult T‐cell leukemia and induces autoimmune disease. Previous analyses of tax transgenic mice suggested that protection of peripheral T‐cells from Fas‐mediated apoptosis by virus‐encoded oncoprotein Tax was relevant to the onset of HTLV‐I‐induced diseases. Here, we show the high level expression of cellular FLICE/caspase‐8‐inhibitory protein (c‐FLIP) in Tax‐expressing HTLV‐I‐infected T‐cells. The silencing of c‐FLIP expression by a lentivirus‐based RNA interference system rendered Tax‐positive HTLV‐I‐infected T‐cells sensitive to Fas‐mediated apoptosis. Exogenously expressed Tax by using a conditional Cre‐loxP‐mediated inducible system also inhibited Fas‐mediated apoptosis by up‐regulating c‐FLIP expression in HTLV‐I‐negative T‐cells. Tax mutant d3 which cannot activate CREB/ATF1, while another M22 mutant which cannot activate NF‐κB did not, suppressed Fas‐mediated apoptosis by inducing c‐FLIP expression. Furthermore, expression of the dominant negative mutant of either NF‐κB or IκBα canceled not only c‐FLIP expression but also inhibitory activity against Fas‐mediated apoptosis by Tax. Inactivation of NFAT, however, did not decrease the expression of c‐FLIP in HTLV‐I‐infected T‐cells. Taken together, Tax inhibits Fas‐mediated apoptosis by up‐regulating c‐FLIP expression in HTLV‐I‐infected cells, and NF‐κB activity plays an essential role in the up‐regulation of c‐FLIP.
Hepatitis C at the Israeli National Hemophilia Center
Authors: MAOR Y. , BASHARI D. , KENET G. , LALEZARI S. , LUBETSKY A. , LUBOSHITZ J. , SCHAPIRO J. M. , AVIDAN B. , BAR‐MEIR S. , MARTINOWITZ U.
Published: January 2006

Summary.  Haemophilia patients who received non‐virucidally treated large pool clotting factors before 1987 have a high rate of chronic hepatitis C viral infection (HCV). Some patients are coinfected with HIV. Haemophilia patients and other coagulation disorders were treated at one centre since the beginning of the 1970, and the Israeli National Hemophilia Center (INHC) was officially founded in 1987. To characterize patients with HCV as well as patients with HCV/HIV coinfection at the INHC. Patients with haemophilia and other coagulation disorders positive for HCV antibodies were evaluated between 2001 and 2004. Demographic data, type and severity of coagulation disorder, frequency of coagulation factor usage and treatment with concentrated clotting factors prior to 1987 were recorded. Liver enzymes, viral load, genotype and data supporting advanced liver disease were evaluated. About 179 of 239 haemophilia patients (75%) tested positive for anti‐HCV antibodies. Our cohort consisted of 165 patients in whom clinical, biochemical and virological data were available. About 117 patients had active HCV infection with HCV‐RNA‐positive, and 27 were HCV/HIV coinfected. Twenty‐one patients (13%) persistently tested HCV‐RNA‐negative, hence were considered to clear their HCV infection. There was no former USSR immigrants among HCV/HIV coinfected compared with HCV‐infected or HCV‐RNA‐negative groups (0 vs. 30% and 38%, respectively; P < 0.001). HCV‐RNA‐negative patients used concentrated coagulation factor less frequently than HCV or HCV/HIV‐infected patients (48% vs. 73%; P = 0.023, and 48% vs. 74%; P = 0.043, respectively). The use of concentrated clotting factors before 1987 was significantly more frequent in HCV/HIV than in either HCV‐infected or HCV‐RNA‐negative patients (96% vs. 49% and 48%, respectively; P < 0.001). Compared with HCV/HIV subjects, patients with HCV monoinfection were characterized by a higher proportion of infection with genotype 1 (80% vs. 61%; P = 0.027). The rate of persistently normal liver enzymes in these patients was higher (24% vs. 7%; P = 0.05) than in the HCV/HIV‐coinfected patients. Advanced liver disease was significantly more common in patients with HCV/HIV‐coinfection than in HCV‐monoinfected patients (11% vs. 3%; P = 0.045). The majority of haemophilia patients are infected with HCV. Viral clearance occurred in a minority of these patients. HCV monoinfected and HCV/HIV coinfected differ clinically and prognostically.
Deep vein thrombosis in a patient with severe haemophilia A
Authors: KASHYAP R. , SHARMA L. M. , GUPTA S. , SAXENA R. , SRIVASTAVA D. N.
Published: January 2006

Summary.  A 25‐year‐old male with severe haemophilia A developed deep vein thrombosis of the left upper limb. Venography showed thrombosis of the basilic vein. There was no underlying prothrombotic condition. He was successfully treated with low‐molecular weight heparin.
Successful induction of immune tolerance by continuous infusion of recombinant factor VIII in a haemophilia A patient with high‐inhibitor titres
Authors: TAMURA K. , KANAZAWA T. , SUZUKI M. , SHIOYA A. , MORIKAWA A.
Published: January 2006

Summary.  The successful and persistent abolition of the inhibitor is of significant clinical benefit, as it allows for the restoration of the usual treatment with clotting factor concentrate. We describe a successful induction of immune tolerance by continuous infusion of recombinant factor VIII (rFVIII) in a 5‐year‐old boy with severe haemophilia A and high‐responding inhibitor. He had previously been subjected to immune tolerance induction (ITI) with rFVIII at 100 units (U) kg−1 three times weekly. One year after the beginning of therapy tolerance was not achieved and a high titer of inhibitor was detected (15 Bethesda Units). The patient had a sudden onset of severe neck pain. The diagnosis of spinal epidural haematoma was revealed by magnetic resonance imaging, and emergency laminectomy with evacuation of the haematoma was required. The patient received sequential therapy for surgery first as bolus rFVIII injection of 500 U kg−1 in order to overwhelm the inhibitor and then as continuous infusion at 6 to 12 U kg−1 hour−1 to avoid bleeding episodes in the postoperative period. After the 3 weeks of continuous infusion, the inhibitor became undetectable. Thereafter, prophylactic treatment with rFVIII was started three times weekly, and the inhibitor has remained undetectable for 6 months. The, present case suggests that continuous infusion of rFVIII may be an effective therapy to induce immune tolerance.
Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia
Authors: LINDVALL K. , COLSTRUP L. , WOLLTER I.‐M. , KLEMENZ G. , LOOGNA K. , GRÖNHAUG S. , THYKJAER H.
Published: January 2006

Summary.  It is well known that teenagers with chronic diseases have problems complying with their treatment. The aim of this study was to evaluate the patient's knowledge of haemophilia and his compliance to prophylactic treatment, and the age at which the patient took over the responsibility for his disease and to create educational material for teenagers and adolescents. This was a prospective multicentre study performed in Hemophilia Treatment Centres in Scandinavia. A total of 108 of 134 patients, between 13 and 25 years completed the questionnaire, a response rate of 80%. Eighty‐three patients had a severe form of haemophilia, 24 patients in moderate form and one patient did not know the severity of his disease. Seventy‐eight patients were on prophylactic treatment. The median age for starting prophylactic treatment was 3.0 years and the median age for the patient performing venepuncture was 11.6 years. Sixty‐seven of 78 patients knew that the best time to give prophylactic treatment was in the morning. Even though the patients were on prophylactic treatment, 47 of 78 patients took additional treatment before sports activities. At a mean age of 14.1 years the patient himself had the responsibility for his disease and treatment. In the cohort of 108 patients, 73 were aware of their haemophilia heredity. This study shows a rather high degree of knowledge of haemophilia and compliance with treatment among the patients but it is of great importance for the nurse to continuously improve the patient's compliance and keep him aware of the benefit of regular treatment for his future well being.
Clinical predictors of in‐hospital mortality in patients with snake bite: a retrospective study from a rural hospital in central India
Authors: Kalantri Shriprakash , Singh Amandeep , Joshi Rajnish , Malamba Samuel , Ho Christine , Ezoua Joseph , Morgan Maureen
Published: January 2006

Objective To determine the association between selected admission risk factors and in‐hospital mortality in patients admitted with venomous snake bite to a rural tertiary care hospital in central India.

Methods Retrospective cohort study of patients aged 12 years or older admitted to a rural hospital in central India between January 2000 and December 2003 with venomous snake bites. The primary endpoint was in‐hospital mortality. We used Cox proportional‐hazards regression analysis to evaluate the association between risk factors (home‐to‐hospital distance, bite‐to‐hospital time, vomiting, neurotoxicity, urine albumin, serum creatinine concentration and whole‐blood clotting time) and in‐hospital mortality.

Results Two hundred and seventy‐seven patients [mean age 32 (SD 12) years; 188 men (68%)] were admitted with venomous snake bite, 29 patients (11%) died. The probability of survival at day 7 was 83%. Vomiting [hazard ratio 6.51 (95% CI 1.94–21.77),P ≤ 0.002], neurotoxicity [hazard ratio 3.15 (95% CI 1.45–6.83),P = 0.004] and admission serum creatinine concentration [hazard ratio 1.35 (95% CI 1.17–1.56),P ≤ 0.001] were associated with higher risk of death in the adjusted analysis.

Conclusions In our rural hospital setting, the overall mortality rate was 11 per 100 cases of snake bite. Vomiting, neurotoxicity and serum creatinine are significant predictors of mortality among inpatients with snake bite. These predictors can help clinicians assess prognosis of their patients more accurately and parsimoniously and also serve as useful signposts for clinical decision‐making.
A 10‐year study of squamous cell carcinoma in Hamedan in the west of Iran (1993–2002)
Authors: Zamanian Abbas , Farshchian Mahmood , Meheralian Azame
Published: January 2006

Background Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer in Caucasians. Environmental factors, especially sunlight, play an important role in its pathogenesis.

Aim To better define the frequency and characteristics of SCC in patients biopsied at Hamedan Sina Hospital in the west of Iran.

Methods This descriptive cross‐sectional study was carried out in patients diagnosed with SCC in the Department of Dermatology, Hamedan Sina Hospital, Hamedan, Iran, in the 10‐year period from 1993 to 2002.

Results From a total of 6846 biopsies, 669 skin cancers were diagnosed, including 449 (66.67%) basal cell carcinomas (BCC) and 179 (26.76%) SCC. The head and face were the most common sites of SCC location. Farming was the most common occupation.

Conclusion SCC is the second most common form of skin malignancy in the west of Iran. Sunlight may play a role in the etiology of this tumor.
Use of systemic glucocorticosteroids in pregnancy: Be alert but not alarmed
Authors: Rennick Gordon J
Published: January 2006

Concerns have been raised regarding the use of repeated courses of systemic glucocorticosteroids given to pregnant women with threatened premature labour to improve fetal lung maturity. Most worrying are animal studies showing detrimental effects on the developing brain, though human data to date are conflicting. Additional concerns relate to the fetal origins of adult diseases, particularly vascular diseases such as hypertension and atherosclerosis. It is currently recommended that obstetricians give only a single course of antenatal corticosteroids to pregnant women to enhance lung maturity instead of giving repeated doses, which was previously a common practice. Other clinicians including dermatologists, gastroenterologists and rheumatologists may have reason to provide systemic glucocorticosteroids to pregnant women. Although systemic glucocorticosteroids all cross the placenta to some degree, the extent to which they do so depends on the drug involved. The choice of systemic glucocorticosteroid for the pregnant women in light of this evolving literature is discussed.
An open‐label, pilot study examining the efficacy of curettage followed by imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma
Authors: Wu Jason K , Oh Carol , Strutton Geoff , Siller Greg
Published: January 2006

The short‐term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de‐bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effictive for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.
Not seeing the ocean for the islands: the mediating influence of matrix‐based processes on forest fragmentation effects
Authors: Kupfer John A. , Malanson George P. , Franklin Scott B.
Published: January 2006

The pervasive influence of island biogeography theory on forest fragmentation research has often led to a misleading conceptualization of landscapes as areas of forest/habitat and ‘non‐forest/non‐habitat’ and an overriding focus on processes within forest remnants at the expense of research in the human‐modified matrix. The matrix, however, may be neither uniformly unsuitable as habitat nor serve as a fully–absorbing barrier to the dispersal of forest taxa. In this paper, we present a conceptual model that addresses how forest habitat loss and fragmentation affect biodiversity through reduction of the resource base, subdivision of populations, alterations of species interactions and disturbance regimes, modifications of microclimate and increases in the presence of invasive species and human pressures on remnants. While we acknowledge the importance of changes associated with the forest remnants themselves (e.g. decreased forest area and increased isolation of forest patches), we stress that the extent, intensity and permanence of alterations to the matrix will have an overriding influence on area and isolation effects and emphasize the potential roles of the matrix as not only a barrier but also as habitat, source and conduit. Our intention is to argue for shifting the examination of forest fragmentation effects away from a patch‐based perspective focused on factors such as patch area and distance metrics to a landscape mosaic perspective that recognizes the importance of gradients in habitat conditions.
Strategic Process Effects on the Entrepreneurial Orientation–Sales Growth Rate Relationship
Authors: Covin Jeffrey G. , Green Kimberly M. , Slevin Dennis P.
Published: January 2006

This research examined the effects of three strategic process variables—strategic decision–making participativeness, strategy formation mode, and strategic learning from failure—on the entrepreneurial orientation (EO)–firm sales growth rate relationship. Results based on a sample of 110 manufacturing firms indicated a positive effect of EO on sales growth rate. Moreover, the relationship between EO and sales growth rate was more positive among firms that employ autocratic decision making and that exhibit an emergent strategy formation process. Perceptions of proficiency at learning from strategic mistakes differentially affected the growth rates of firms at different ends of the EO continuum, but in manners inconsistent with the hypothesized relationship.
Evaluation of the efficacy of oral deferiprone in β‐thalassemia major by multislice multiecho T2*
Authors: Pepe Alessia , Lombardi Massimo , Positano Vincenzo , Cracolici Eliana , Capra Marcello , Malizia Roberto , Prossomariti Luciano , De Marchi Daniele , Midiri Massimo , Maggio Aurelio
Published: January 2006

Abstract:  Objectives: Oral deferiprone (L1) appears to be promising in the treatment of β‐thalassemia major (TM) patients. T2* magnetic resonance imaging (MRI) with a single measurement in the mid‐ventricular septum was validated as a quantitative evaluation of myocardial iron overload. Previous studies suggested a marked heterogeneity of iron distribution in the myocardium. We set up a multislice multiecho T2* MRI for the detection of this heterogeneity. The aim of our study was to investigate differences between the L1 vs. the subcutaneous desferrioxamine (DF)‐treated patients using this new approach.Methods: Thirty‐six β‐TM patients (age 29 ± 8 yr) underwent MRI. Eighteen patients received long‐term L1, and 18 other patients matched for age and sex received DF. T2* multiecho sequences on three short axis views of the left ventricle were obtained and analyzed by custom‐made software. In each slice, the myocardium was automatically segmented into four segments. Cine‐dynamic images were also obtained to evaluate biventricular function.Results: For multislice T2* technique, the coefficient of variation for intra‐ and inter‐observer, and inter‐study reproducibility was 3.9%, 4.7%, and 5.5%, respectively. The global heart T2* value was significantly higher in the L1 vs. DF group (35 ± 7 vs. 27 ± 2 ms; P = 0.02). The number of segments with normal T2* value (>20 ms) was significantly higher in the L1 vs. the DF group (11 ± 1 vs. 8 ± 5 segments; P = 0.03). We did not detect significant differences in biventricular function parameters.Conclusions: This new approach confirms that L1 could be more effective than DF in removal of myocardial iron.
Quantification of chimerism within peripheral blood, bone marrow and purified leukocyte subsets: comparison of singleplex and multiplex PCR amplification of short tandem repeat (STR) loci
Authors: Beck O. , Seidl C. , Lehrnbecher T. , Kreyenberg H. , Schwabe D. , Klingebiel T. , Seifried E. , Bader P. , Koehl U.
Published: January 2006

Abstract:  Objective and Methods: Chimerism analysis has become a routine diagnostic procedure after haematopoietic allogeneic stem cell transplantation for early detection of relapse of disease or graft failure. Whereas some centres developed individual in‐house short tandem repeat (STR) systems, others prefer commercial multiplex PCR systems. However, little is known about inter‐assay variation, which could have a significant impact on treatment decision. We therefore compared two commercial multiplex PCR kits with our in‐house STR system using different sample sources, such as peripheral blood (PB), bone marrow (BM) and specific leukocyte subsets.Results: Fifty samples of eighteen paediatric patients were analysed. For neither material, PB, BM and leukocyte subtypes, a significant difference between the STR systems tested was observed. Chimerism analyses of each single STR primer, which is component of both the in‐house and the commercial STR system, did not reveal significant differences.Conclusion: Our analysis demonstrates that similar results can be obtained with both assays, even when using various sample sources. Further evaluation of different test systems will help to increase interlaboratory standardisation of chimerism analyses for early clinical intervention.
Sickle cell anemia in Guadeloupean children: pattern and prevalence of acute clinical events
Authors: Tarer Vanessa , Etienne‐Julan Maryse , Diara Jean‐Pierre , Belloy Marie Sylvaine , Mukizi‐Mukaza Martin , Elion Jacques , Romana Marc
Published: January 2006

Abstract:  We analyzed the records of 153 Guadeloupean children with sickle cell anemia (SCA), for whom clinical and laboratory data were prospectively collected (mean follow‐up duration 8.4 ± 4.6 yr). Prevalence and age‐specific frequencies of acute clinical events were determined and correlations between complications, hematological parameters and potential modulating factors investigated. Painful crisis and acute chest syndrome (ACS) were the two most common complications, affecting 65.4% and 58.8% of the patients, respectively. The frequency of acute anemia was 49.7% (acute splenic sequestration 24.8%; acute aplastic anemia 15.0%). Prevalences of septicemia‐meningitis and osteomyelitis were 15.7% and 16.3%, respectively. A higher incidence of infections, painful crises and acute anemia was detected in patients who developed ACS. The well‐documented protective effect of HbF level on the overall disease expression was observed with higher HbF level in asymptomatic than in symptomatic patients (17.5% ± 8% vs. 9.9% ± 6.4%, P = 0.01) with similar ages and sex ratio. It was also confirmed on ACS and, for the first time, further extended to acute anemic events and septicemia. Besides its effect on hematological parameters, α‐thalassemia seems to have little impact on the prevalence of complications, as do βS‐globin haplotypes. Comparison with other series suggests that the natural history of SCA in Guadeloupe is more similar to that in Jamaica with regard to those reported in Europe and the United States, suggesting a potential impact of environmental factors on the clinical course of the disease.
Marrow aplasia developing 13 years after HLA‐identical sibling allogeneic transplantation for chronic myeloid leukaemia: successful treatment with antithymocyte globulin and peripheral blood stem cell infusion from the original donor
Authors: O'Donghaile D , Hayden P. J. , McCarron S. L. , Doyle E. M. , Lawler M. , Browne P. V. , Conneally E. , Vandenberghe E. , McCann S. R.
Published: January 2006

Abstract:  Secondary or late graft failure has been defined as the development of inadequate marrow function after initial engraftment has been achieved. We describe a case of profound marrow aplasia occurring 13 years after sibling allogeneic bone marrow transplantation for chronic myeloid leukaemia (CML) in first chronic phase. Although the patient remained a complete donor chimera, thereby suggesting that an unselected infusion of donor peripheral blood stem cells (PBSC) or bone marrow might be indicated, the newly acquired aplasia was thought to be immune in aetiology and some immunosuppression was therefore considered appropriate. Rapid haematological recovery was achieved after the infusion of unselected PBSC from the original donor following conditioning with anti‐thymocyte globulin (ATG).