bluuebunny/crossref_metadata_2025 huggingface dataset:
RabGEF1 regulates stem cell factor/c-Kit-mediated signaling events and biological responses in mast cells
Authors: Kalesnikoff Janet , Rios Eon J. , Chen Ching-Cheng , Nakae Susumu , Zabel Brian A. , Butcher Eugene C. , Tsai Mindy , Tam See-Ying , Galli Stephen J.
Published: February 2006

We recently reported that RabGEF1 is a negative regulator of high-affinity Fc receptor for IgE (FcεRI)-dependent mast cell activation and that mice lacking RabGEF1 develop severe skin inflammation and increased numbers of dermal mast cells. To better understand how RabGEF1 can regulate signaling events and biological responses in mast cells, we examined the responses of bone marrow-derived cultured mast cells (BMCMCs) from wild-type (+/+) andRabgef1knockout (−/−) mice after stimulation with the c-Kit ligand, stem cell factor (SCF), an important regulator of mast cell development, survival, proliferation, and activation. We found that RabGEF1-deficient mast cells exhibited enhanced and prolonged activation of Ras and extracellular regulated kinase, and significantly elevated IL-6 secretion, after stimulation with SCF. SCF-induced activation of c-Jun N-terminal kinase was increased inRabgef1−/−BMCMCs, but without corresponding significant increases in SCF-induced migration or adhesion. SCF-mediated activation of the survival-enhancing kinase, Akt, also was increased inRabgef1−/−BMCMCs, and these cells had a survival advantage over their +/+ counterpartsin vitro. Despite enhanced Ras activation in the absence of RabGEF1, SCF-induced proliferation was lower inRabgef1−/−BMCMCs compared with their +/+ counterparts. Finally, we found that c-Kit internalization was delayed in the absence of RabGEF1, probably reflecting a positive role for RabGEF1 in the regulation of endocytic events, and that infection ofRabgef1−/−BMCMCs with a wild-type RabGEF1 lentiviral construct normalized c-Kit internalization to the levels seen in +/+ BMCMCs. Thus, RabGEF1 plays a critical role in the regulation of SCF/c-Kit-mediated signaling events and biological responses in mast cells.
The effect of ingestion of inulin on blood lipids and gastrointestinal symptoms in healthy females
Authors: Pedersen Anette , Sandström Brittmarie , Van Amelsvoort Johan M. M
Published: February 2006

The effect of a daily intake of 14g inulin added to a low-fat spread on fasting blood lipids and gastrointestinal symptoms was investigated in sixty-four young healthy women in a randomized double-blind crossover study involving two periods of 4 weeks. The test spread with and without inulin replaced habitual spread during the test periods. No significant differences between the test periods in plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triacylglycerol concentrations were observed. Gastrointestinal symptoms assessed with questionnaires showed that in the inulin period there was a significantly (P<0·05) higher degree of discomfort from flatulence and other gastrointestinal symptoms than in the control period. In general, there was no indication of intestinal adaptation to this level of intake of inulin.
Influence of foliage from African multipurpose trees on activity of rumen protozoa and bacteria
Authors: Newbold C.J , El Hassan S. M. , Wang* J , Ortega M.E , Wallace R.J
Published: February 2006

Samples and extracts of foliage from African multipurpose trees were screened for their effects on rumen protozoa and bacteria with a view to predicting their safety as feed supplements and for identifying species with potential antiprotozoal activity. The species tested wereAcacia aneura, Charnaecytisus palmensis, Brachychiton populneum, Flindersia maculosa, Sesbania sesban, Leucaena leucocephalaandVernonia amyedalina. Antimicrobial effects were mild except forS. sesban, which was highly toxic to rumen protozoain vitro, andA. aneura, which was toxic to rumen bacteria. The antiprotozoal factor inS. sesbanwas apparently associated with the fraction of the plant containing saponins. WhenS. sesbanwas fed to sheep, protozoal numbers fell by 60 % after 4 d, but the population recovered after a further 10 d.In vitroexperiments demonstrated that washed protozoa from later times were no more resistant toS. sesbanthan on initial exposure, suggesting that other micro-organisms, probably the bacteria, adapted to detoxify the antiprotozoal agent. ThusS. sesbanmay be useful in suppressing protozoa and thereby improving protein flow from the rumen, but only if the bacterial metabolism of the antiprotozoal factor can be avoided.
Broiler chicken body weights, feed intakes, plasma lipid and small-intestinal bile acid concentrations in response to feeding of chitosan and pectin
Authors: Razdan A. , Pettersson D. , Pettersson J.
Published: February 2006

One-day-old broiler chickens were fed on a control diet based on maize and maize starch or diets containing 30g/kg of 89 % deacetylated chitin (chitosan) or low-methoxyl (34 % degree of esterification) pectin. Feeding of the chitosan diet to chickens significantly reduced body weights and feed intakes compared with animals fed on control or pectin diets on days 5 and 11 of the experiment. On day 12, significant reductions in total plasma cholesterol and HDL-cholesterol concentrations were observed among birds fed on the chitosan but not the pectin diet in relation to control-fed animals. A concomitant increase in the plasma HDL-cholesterol:total cholesterol ratio was observed among chitosan-fed chickens. The generally reduced concentrations of primary and total bile acids in the duodenum of birds fed on the fibre-containing diets on day 13 may have been an indication of a delay in the production and/or secretion of bile. Viscosity of the three broiler-chicken diets was measured after suspension in water, acidification and finally neutralization of the suspensions, in an attempt to simulate the effect of changes in pH and dilution of diets occurring in the gizzard and small intestine of chickens. Viscosity of the chitosan diet was significantly elevated after acidification and significantly reduced at neutralization in comparison with the control and pectin-containingdiets suggesting that the hypolipidaemic influence of chitosan observed in the present study may be due to interruption of enterohepatic bile acid circulation rather than increased viscosity in the small intestine of chickens. The low viscosity of the pectin dietin vitrotogether with the absence of a hypocholesterolaemic effect of this diet when fedin vivoprecludes any conclusion regarding the hypocholesterolaemic mechanism of pectin observed in earlier studies.
Closing the Savings Gap? The Role of the Saving Gateway
Authors: Collard Sharon , Mckay Stephen
Published: February 2006

The 2001 election manifesto committed Labour to introducing two innovative policies designed to increase savings and assets among future generations, and the low-income families of today. The Child Trust Fund aims to provide all children with an endowment of assets when they reach the age of 18. Child Trust Fund accounts became available in April 2005 to all children born from 1 September 2002. The Saving Gateway offers a new savings account for lower-income families, designed to encourage savings. The first Saving Gateway pilot took place between 2002 and 2004; a second, larger pilot is currently underway. This article outlines the key findings from the evaluation of the first Saving Gateway pilot.1 Overall, the results are positive—the scheme has encouraged participants to save, and to save regularly. In addition, it seems to have resulted in positive psychological and attitudinal changes among a significant proportion of participants.
Evaluation of flexion/extension of the upper cervical spine in patients with rheumatoid arthritis: an MRI study with a dedicated positioning device compared to conventional radiographs
Authors: Karhu J. O. , Parkkola R. K. , Koskinen S. K.
Published: February 2006

Purpose: Using flexion/extension magnetic resonance imaging (MRI) with a dedicated positioning device, our purpose was to analyze pathologic cranio‐vertebral joint anatomy and motion in patients with rheumatoid arthritis in comparison to normal patients, and to compare flexion/extension MRI with conventional radiographs (CRs) in patients with rheumatoid arthritis.

Material and Methods: The 31 patients with rheumatoid arthritis and 20 healthy subjects included in the study were imaged in an open MRI scanner during flexion/extension. A dedicated positioning device was used. Additionally, we compared flexion/extension MRI with CRs in patients with rheumatoid arthritis. In MRI, the orientation and segmental motion of C0, C1, and C2 were assessed and structure of the dens and amount of pannus tissue were observed. Configuration of the cerebrospinal fluid space and the cord was evaluated in each position. In both MRI and CRs, anterior atlanto‐axial subluxation and vertical dislocation were assessed and sagittal diameter of the dural sac was measured.

Results: In the neutral position, C1 of the patients was oriented in a more flexed position in relation to both C0 and C2 compared to that in healthy subjects. The patients had more extension in the upper cervical spine than did healthy subjects. In flexion, atlanto‐axial subluxation was greater in CRs than in MRI. In MRI, the amount of vertical dislocation did not depend on position. In the patients, there was considerably more cord impingement in flexion than in other positions.

Conclusion: Evaluation of the rheumatoid cervical spine is optimized using MR images in the neutral, flexed, and extended positions. Measurements and relationships between structures should be compared in all positions. CRs with flexion‐extension views are recommended as the first imaging method.
Pulmonary vascular dilation induced by l‐arginine: correlation with induction of endothelial nitric oxide synthase in a rabbit model
Authors: Yoon S. K. , Lee K.‐N. , Lee J. H. , Jeong J. S. , Kwak J.‐Y.
Published: February 2006

Purpose: To determine whether oral administration of l‐arginine induces pulmonary vascular dilation, and if this pulmonary vascular dilation correlates with induction of endothelial nitric oxide synthase (eNOS) in a rabbit model.

Material and Methods: Seven rabbits were fed with l‐arginine dissolved in tap water. The degree of pulmonary vascular dilation was determined using thin‐section computed tomography and the concentration of serum nitrite was measured. They were compared with four control animals. The pulmonary vascular dilation was correlated to serum levels of nitrite. Lung tissues were examined for induction of eNOS by immunohistochemistry.

Results: An increased degree of pulmonary vascular dilation was found in the l‐arginine‐fed group compared to the control group ( P<0.05). Serum levels of nitrite in the l‐arginine‐fed group were higher than those in the control group ( P<0.05). Pulmonary vascular dilation correlated with serum levels of nitrite ( r2 = 0.95, P<0.05). Induction of eNOS was increased in the l‐arginine‐fed group.

Conclusion: The administration of l‐arginine causes pulmonary vascular dilation, which is most likely mediated via nitric oxide through increased induction of eNOS in a rabbit model.
Endoanal magnetic resonance imaging of fistula‐in‐ano: a comparison of stir with gadolinium‐enhanced techniques
Authors: Szyszko T. A. , Bush J. , Gishen P. , Sellu D. , DeSouza N. M.
Published: February 2006

Purpose: To compare a STIR sequence with gadolinium‐enhanced techniques on endoanal magnetic resonance (MR) imaging of fistulas‐in‐ano by correlating the findings with those at surgery.

Material and Methods: Twenty‐two consecutive patients with clinical suspicion of perianal sepsis were studied using an endoanal coil followed immediately by a phased array coil. T1‐weighted precontrast and postcontrast and STIR images in transverse and coronal planes were produced with each coil and analysed by noting the presence and site of a collection, primary track, the position of any internal opening, and subcutaneous or supralevator extension. An “expert” and also a “trainee” radiologist assessed the images. Operative findings were similarly recorded. The Fisher exact test was used to compare imaging with surgery. Interobserver variation was calculated using a kappa statistic.

Results: Of 22 patients with suspected fistulas, 8 were simple, 4 were complex, and 3 were superficial sinuses. Five had no anal pathology, 1 had anal excoriation, and 1 had a polyp. At surgery, 6 intersphincteric, 1 transsphincteric, 8 extrasphincteric, no supralevator collections, and 9 internal openings were noted. The overall sensitivity and specificity for detecting these were 75% and 64%, respectively, for STIR imaging, and 58.3% and 62.8% for gadolinium‐enhanced imaging. There was good agreement between the “trainee” and the “expert” in the interpretation of images (kappa = 0.7).

Conclusion: A STIR sequence is more sensitive overall than gadolinium‐enhanced techniques on endoanal magnetic resonance imaging of fistulas‐in‐ano because of increased sensitivity in detecting the internal opening. A combination of endoanal and phased array techniques using STIR imaging sequences is valuable preoperative assessment in both simple and complex cases.
Ultrasonographic findings in ceftriaxone: associated biliary sludge and pseudolithiasis in children
Authors: Ozturk A. , Kaya M. , Zeyrek D. , Ozturk E. , Kat N. , Ziylan S. Z.
Published: February 2006

Purpose: To prospectively evaluate the incidence of biliary sludge and pseudolithiasis in children treated with ceftriaxone.

Material and Methods: Thirty‐three children (14 girls, 19 boys) treated with ceftriaxone for prophylaxis ( n = 13) or for an infection ( n = 20) were included in this study. The incidences of biliary sludge and pseudolithiasis were investigated using ultrasonography. The ultrasonographic evaluations were performed prior to and on the 4th–5th days and on the 8th–10th days of treatment. The patients who had biliary sludge or pseudolithiasis were followed up with ultrasonographic evaluation periodically until these pathological phenomena disappeared.

Results: Ceftriaxone was administrated intravenously at a dosage of 100 mg kg−1 day−1. Serial gallbladder sonograms were performed before treatment and on the 4th–5th and 8th–10th days of therapy. Nineteen children developed pseudolithiasis and sludge in the gallbladder, and all were asymptomatic. No significant differences were found between the patients with normal versus abnormal sonographic findings in regard to gender, age, duration of the therapy, oral restriction except the presence of surgery ( P<0.005).

Conclusion: The combination of oral restriction and surgical procedures may be a causal factor in ceftriaxone‐associated biliary pseudolithiasis. It is emphasized that when gallstone and/or sludge are detected in the gallbladder in children by ultrasonographic examination, the administration of ceftriaxone must be sought beyond other causative factors.
Magnetic resonance myelography evaluation of the lumbar spine end plates and intervertebral disks
Authors: Mollà E. , Martí‐Bonmatí L. , Arana E. , Martinez‐Bisbal M. C. , Costa S.
Published: February 2006

Purpose: To evaluate the value of magnetic resonance (MR) myelography in the evaluation of intervertebral disk and end‐plate degenerative changes in the lumbar spine.

Material and Methods: Conventional MR and MR myelography examinations were performed in 150 consecutive patients (69 F and 81 M, mean age 45±15 years, range 18–89). Sagittal T1 and T2‐weighted TSE images were compared to MR myelography obtained with a multishot‐TSE‐T2‐weighted sequence (4000/250/fat suppression). Coronal, sagittal, and both oblique MR myelography projections were obtained. Image analysis was carried out independently by two radiologists who categorized lumbar disks into normal, degenerated, or edematous; and vertebral end plates into normal, edematous, or with fatty changes. The proportions were statistically compared at every lumbar intervertebral level.

Results: There was good agreement in the classification of disk disease (Kappa: 0.8–0.9). MRI detected a larger number of disk degeneration and end‐plate fatty metamorphosis, while the MR myelography technique depicted a larger number of edematous disks and end plates.

Conclusion: MR myelography was of limited value in detecting the same vertebral end‐plate changes observed in MRI, although with similar findings in disk disease. However, the higher detection of edema changes by MR myelography should be analyzed prospectively, as it could be more sensitive than conventional MR sequences.
Standard orientation of the pelvis: validation on a model and ten patients
Authors: Olivecrona L. , Aspelin P. , Weidenhielm L. , Stark A. , Noz M. E. , Maguire G. Q. , Zeleznik M. P. , Svensson L. , Olivecrona H.
Published: February 2006

Purpose: To validate an image post‐processing method for re‐orienting the pelvis in CT volumes to a standardized orientation in a model and in 10 patients.

Material and Methods: Twenty‐four CT volumes of a pelvic model and 10 pairs of postoperative total hip arthroplasty (THA) patient CT scans were rotated to a defined pelvic standard orientation and the rotation was recorded. For precision, a test‐retest procedure was used. For accuracy, three exactly represented coordinate points were used. For clinical application, the standard orientation was used for calculating the direction of acetabular cup migration from a previous model study.

Results: Precision of pelvic standard orientation, calculated as maximal directional error, was better than 1° in the model study and better than 1.5° in the patient study. Accuracy, expressed as angle between ideal and measured coordinate axes, was 0.1° for x, y, z axes. No measurable systematic errors were found. When applied to acetabular cup migration in the model, standardization of pelvic orientation had no significant effect on the measurements.

Conclusion: Reorienting the pelvis during image post‐processing was shown to be accurate. It enables measurements relative to the pelvis and minimizes the dependency of patient positioning.
Preoperative assessment of focal liver lesions: multidetector computed tomography challenges magnetic resonance imaging
Authors: Numminen K. , Isoniemi H. , Halavaara J. , Tervahartiala P. , Mäkisalo H. , Laasonen L. , Höckerstedt K.
Published: February 2006

Purpose: To investigate prospectively multidetector computed tomography (CT) (MDCT) and magnetic resonance (MR) imaging (MRI) in the preoperative assessment of focal liver lesions.

Material and Methods: Multiphasic MDCT and conventional gadolinium‐enhanced MRI were performed on 31 consecutive patients prior to hepatic surgery. All images were blindly analyzed as consensus reading. Lesion counts and their relation to vascular structures and possible extrahepatic disease were determined. The data from the MDCT and MRI were compared with the results obtained by intraoperative ultrasound (IOUS) and palpation. Histopathologic verification was available.

Results: At surgery, IOUS and palpation revealed 45 solid liver lesions. From these, preoperative MDCT detected 43 (96%) and MRI 35 (78%) deposits. MDCT performed statistically better than MRI in lesion detection ( P = 0.008). Assessment of lesion vascular proximity was correctly determined by MDCT in 98% of patients and by MRI in 87%. Statistical difference was found ( P = 0.002). IOUS and palpation changed the preoperative surgical plan as a result of extrahepatic disease in 8/31 (26%) cases. In MDCT as well in MRI extrahepatic involvement was suspected in two cases.

Conclusion: MDCT was superior to MRI and nearly equal to IOUS in liver lesion detection and in the determination of lesion vascular proximity. However, both techniques fail to reliably detect extrahepatic disease.
Multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis
Authors: Kobayashi T. , Satoh K. , Ohkawa M.
Published: February 2006

A case of multifocal micronodular pneumocyte hyperplasia (MMPH) associated with tuberous sclerosis is reported. MMPH is a rare pulmonary disorder characterized by the nodular proliferation of type II pneumocytes. In the case presented here, MMPH appeared as multiple, well‐defined small nodules with ground‐glass opacity. It is necessary to consider MMPH when small nodules with ground‐glass opacity are observed on HRCT in patients with tuberous sclerosis.
Magnetic resonance imaging and diffusion‐weighted imaging in methylmalonic acidemia
Authors: Yeşildağ A. , Ayata A. , Baykal B. , Koroglu M. , Yıldız H. , Oral B. , Oktem F. , Oyar O.
Published: February 2006

Methylmalonic acidemia (MMA) is an inborn disorder of amino acid metabolism, often presenting with neurological symptoms. We present the results of magnetic resonance imaging (MRI) and diffusion‐weighted imaging (DWI) of the brain in a 16‐month‐old male patient with classic neurological and laboratory findings for MMA. MRI demonstrated the hyperintensity within globi pallidi both on T2‐weighted image and DWI during the acute episode of metabolic acidosis.
Lhermitte‐duclos disease associated with neurofibromatosis type‐1 and non‐ossifying fibroma
Authors: Yesildağ A. , Baykal B. , Ayata A. , Kerman G. , Koroglu M. , Olgar S. , Oyar O.
Published: February 2006

Lhermitte‐Duclos disease (LDD) is a rare cerebellar disorder of uncertain pathogenesis characterized by enlargement of cerebellar folia. Magnetic resonance imaging is the diagnostic modality of choice and usually distinguishes the LDD by its characteristic “striated or laminated pattern” appearance. Various additional abnormalities have been reported in association with LDD. We report a case of LDD coexisting with neurofibromatosis type 1 (NF‐1) and non‐ossifying fibroma.
Amplified Molecular Binding of Prion Protein Homologues in Self‐Progressive Injury of Neuronal Membranes and Trafficking Systems
Authors: Agius Lawrence M.
Published: February 2006

Prion particles might be viewed as essential sources of cyclical coupling and uncoupling of depolarization and repolarization of the neuronal plasmalemma. In terms of different parametric functions, the cellular PrPc, both as a source and also a mediated means of induced replication of the Prion particle PrPsc, would be considered in terms of agent amplification as induced by the bovine host. One might view bovine spongiform disease as a source of variant Creutzfeldt‐Jakob disease in the human that would involve such amplified uncoupling of membrane‐based phenomena of ion‐determined polarization events. It would, in addition, appear that a spongiform change of neurons that progresses in conjunction with neuropil alterations and as a primarily self‐amplified system of spreading progression in the brain would necessarily constitute a reactive series of cell injury. It is indeed in terms of a neuronal reactivity linked, for example, to mitochondrial overactivity and also to perhaps nucleotide inserts within neurons that one might consider species specificity of prion particle transmission a host‐based series of events giving rise to and constituting also a final expression of disease process events.

It might be realistic to consider interspecies transmissibility, and once this occurs, a fundamental pathway of evolutionary adaptability that arises and progresses simply in terms of progressively amplified reactivity.

Reactivity to neuronal injury would appear an integral system of self‐progression based on a primary and also a series of secondary changes that evolve in terms of a PrPc particle that itself promotes self‐conversion to PrPsc. Indeed, conformational changes to PrPsc might be defined as a system disorder of neuronal reactivity that self‐progresses as amplified progressiveness of the neuronal injury.
A Model Incorporating Some of the Mechanical and Biochemical Factors Underlying Clot Formation and Dissolution in Flowing Blood
Authors: Anand M. , Rajagopal K. , Rajagopal K. R.
Published: February 2006

Multiple interacting mechanisms control the formation and dissolution of clots to maintain blood in a state of delicate balance. In addition to a myriad of biochemical reactions, rheological factors also play a crucial role in modulating the response of blood to external stimuli. To date, a comprehensive model for clot formation and dissolution, that takes into account the biochemical, medical and rheological factors, has not been put into place, the existing models emphasizing either one or the other of the factors. In this paper, after discussing the various biochemical, physiologic and rheological factors at some length, we develop a model for clot formation and dissolution that incorporates many of the relevant crucial factors that have a bearing on the problem. The model, though just a first step towards understanding a complex phenomenon, goes further than previous models in integrating the biochemical, physiologic and rheological factors that come into play.
Non‐Linear Analysis Approach of Maternal Heart Rate Patterns in Normal and Pre‐Eclamptic Pregnancies
Authors: Salazar Carlos , Torres Joel , Nieto-Villar José M.
Published: February 2006

Identification of the pregnant woman prone to develop pre‐eclampsia later during her course of the pregnancy is a clinical challenge in clinical obstetrics. A new and non‐invasive approach to detect abnormalities in pre‐eclamptic women that differentiate from women with uneventful pregnancies is presented here. We applied non‐linear and fractal features for classifying the dynamical complexity of the heart rate (HR) patterns corresponding to seven normal subjects and eight pre‐eclamptic patients. Significant differences in the estimated largest Lyapunov exponent and in the correlation dimension between normotensive women and those with pre‐eclampsia were found, suggesting they may have potential as new markers for pre‐eclampsia. HR patterns in healthy and pre‐eclamptic pregnancies correspond to complex non‐linear dynamics, which could arise from the contribution of stochastic and chaotic components. HR of pre‐eclamptic patients also revealed a more regular dynamic behavior than those belonging to normal pregnancies, corroborating the general observation that diseased states may be associated with regular HR patterns.
Viral Interactions with the Nuclear Transport Machinery: Discovering and Disrupting Pathways
Authors: Fontoura Beatriz MA , Faria Paula A. , Nussenzveig Daniel R.
Published: February 2006

Viruses have been invaluable tools for discovering key pathways of nucleocytoplasmic transport. Conversely, disruption of specific nuclear transport pathways, are crucial for the productive life cycle of some viruses. The major cellular mRNA export pathway, which uses TAP (NXF1)/p15(NXT) as receptor, was discovered as a result of TAP interaction with CTE‐containing RNAs from Mason‐Pfizer Monkey Virus. In addition, CRM1 or exportin 1, which is a transport receptor that mediates nuclear export of proteins, snRNAs, rRNAs and a small subset of mRNAs, was discovered as an interacting partner of the Rev protein of HIV1. Viruses may disrupt the nuclear transport machinery to prevent host antiviral response. VSV Matrix (M) protein inhibits mRNA export by forming a complex with the mRNA export factor Rae1 whereas poliovirus inhibits nuclear import of proteins by probably degrading Nup62 and Nup153. Hence, this review focuses on viruses as tools and as disruptors of nucleocytoplasmic trafficking.
IUBMB Life, 57: 65‐72, 2005
Mechanisms of Persistent NF‐κB Activation by HTLV‐I Tax
Authors: Harhaj Edward W. , Harhaj Nicole S.
Published: February 2006

Human T cell leukemia virus type I (HTLV‐I) is the causative agent of a fatal malignancy known as adult T cell leukemia (ATL). The HTLV‐I Tax protein is thought to play a significant role in the initiation and pathogenesis of HTLV‐I‐mediated disease. Tax is a potent oncogene that deregulates cellular gene expression by persistently activating signaling pathways such as NF‐κB. Tax activation of NF‐κB is critical for the immortalization and survival of HTLV‐I‐infected T cells. In this review, we describe recent insights into the mechanisms employed by Tax to activate the canonical and noncanonical NF‐κB signaling pathways. The adaptor function of Tax appears to be a common and important mechanism for the pathological activation of both NF‐κB pathways.
IUBMB Life, 57: 83‐91, 2005
Rpb4 and Rpb7: A Sub‐complex Integral to Multi‐subunit RNA Polymerases Performs a Multitude of Functions
Authors: Sampath Vinaya , Sadhale Parag
Published: February 2006

Rpb4 and Rpb7, are conserved subunits of RNA polymerase II that play important roles in stress responses such as growth at extreme temperatures, recovery from stationary phase, sporulation and pseudohyphal growth. Recent reports have shown that apart from stress response, these proteins also affect a multitude of processes including activated transcription, mRNA export, transcription coupled repair etc. We propose a model that integrates the multifarious roles of this sub‐complex. We suggest that these proteins function by modulating interactions of one or more ancillary factors with the polymerase leading to specific transcription of subsets of these genes. Preliminary experimental evidence in support of such a model is discussed.
IUBMB Life, 57: 93‐102, 2005
Evidence for Rat Organic Anion Transporter 3 Association with Caveolin‐1 in Rat Kidney
Authors: Kwak Jin‐Oh , Kim Hyun‐Woo , Song Joon Ho , Kim Moon‐Jae , Park Hyeon‐Seon , Hyun Dong‐Keun , Kim Dong Soo , Cha Seok Ho
Published: February 2006

The rat organic anion transporter 3 (rOAT3) has recently been identified as the third isoform of the OAT family. The mechanisms that regulate rOAT3's functions remain to be elucidated. rOAT3 contributes for moving a number of negatively charged organic compounds between cells and their extracellular milieu. Caveolin (Cav) also plays a role as a membrane transporter. To address the relationship of these two proteins, we investigated the protein‐protein interaction between rOAT3 and Cav‐1. The rOAT3 mRNA and protein expression were observed in the rat kidney, and the expressions of Cav‐1 mRNA and protein were also detected in the kidney. Confocal microscopy of the immuno‐cytochemistry experiments using primary cultured renal proximal tubular cells showed that rOAT3 and Cav‐1 were co‐localized at the plasma membrane. This finding was confirmed by Western blot analysis using isolated caveolae‐enriched membrane fractions from the rat kidney and immuno‐precipitation experimentation. When rOAT3's synthesized cRNA of rOAT3 along with the antisense oligo deoxynucleotide of Xenopus Cav‐1 were co‐injected into Xenopus oocytes, the [3H] estrone sulfate uptake was significantly decreased. These findings suggest that rOAT3 and caveolin‐1 share a cellular expression in the plasma membrane and Cav‐1 up‐regulates the organic anionic compound uptake via rOAT3 under normal physiological conditions.
IUBMB Life, 57: 109‐117, 2005
Regulation of peripheral T cell activation by calreticulin
Authors: Porcellini Simona , Traggiai Elisabetta , Schenk Ursula , Ferrera Denise , Matteoli Michela , Lanzavecchia Antonio , Michalak Marek , Grassi Fabio
Published: February 2006

Regulated expression of positive and negative regulatory factors controls the extent and duration of T cell adaptive immune response preserving the organism's integrity. Calreticulin (CRT) is a major Ca2+ buffering chaperone in the lumen of the endoplasmic reticulum. Here we investigated the impact of CRT deficiency on T cell function in immunodeficient mice reconstituted with fetal liver crt−/− hemopoietic progenitors. These chimeric mice displayed severe immunopathological traits, which correlated with a lower threshold of T cell receptor (TCR) activation and exaggerated peripheral T cell response to antigen with enhanced secretion of inflammatory cytokines. In crt−/− T cells TCR stimulation induced pulsatile cytosolic elevations of Ca2+ concentration and protracted accumulation of nuclear factor of activated T cells in the nucleus as well as sustained activation of the mitogen-activated protein kinase pathways. These observations support the hypothesis that CRT-dependent shaping of Ca2+ signaling critically contributes to the modulation of the T cell adaptive immune response.
René Dubos: unearthing antibiotics
Authors: Van Epps Heather L.
Published: February 2006

In 1939, René Dubos discovered gramicidin—the first clinically tested antibiotic agent. This discovery helped revive the stalled interest in penicillin and launched the era of antibiotics.
Tuberculosis Among Adult Visitors of Children With Suspected Tuberculosis and Employees at a Children's Hospital
Authors: Muñoz Flor M. , Ong Lydia T. , Seavy Diane , Medina Denise , Correa Armando , Starke Jeffrey R.
Published: February 2006

Objective:

Few children with tuberculosis (TB) have communicable disease, and most do not require isolation within the hospital. However, parents or adult visitors with unrecognized pulmonary TB may be a threat to hospital staff and other patients. We prospectively evaluated adults accompanying children hospitalized for suspected TB at a children's hospital to determine the frequency of undiagnosed, potentially contagious disease.

Methods:

From 1992 to 1998, chest radiographs were obtained from adult caretakers accompanying 59 consecutive children admitted to Texas Children's Hospital with suspected TB. A child and his or her family were placed under Airborne Precautions only if the child or the accompanying adult exhibited characteristics of potentially contagious disease. Annual rates of tuberculin skin test conversion in hospital employees were obtained for the same period.

Results:

Of the 105 screened adults, 16 (15%) had previously undetected pulmonary TB. These adults were associated with 14 (24%) of the 59 children. In all instances in which the adult was the patient's parent, he or she was the source of infection to the child. Only 8 (13.5%) of the 59 children required isolation. Tuberculin skin test conversion from a negative to a positive reaction occurred in 127 employees (8 per 1,000 employee-years at risk). Only 4 of these 127 employees performed activities involving direct patient contact. None was in contact with families with a known potentially contagious adult or pediatric patient.

Conclusions:

The risk of infection of healthcare workers from pediatric patients with primary TB appeared to be minimal, and most children with TB did not need isolation. Infection control efforts should be focused on accompanying adults and adult visitors. (Infect Control Hosp Epidemiol 2002;23:568-572).
Congenital Tuberculosis and Management of Exposures in a Neonatal Intensive Care Unit
Authors: Laartz Brent W. , Narvarte Hugo J. , Holt Douglas , Larkin Julie A. , Pomputius William F.
Published: February 2006

Objective:

We report a case of congenital tuberculosis in a neonatal intensive care unit (NICU) and the management of exposure to other neonates in the hospital. We review the literature regarding congenital tuberculosis and management of exposures in the NICU.

Design:

Case report and a survey of exposures with a 3-month follow-up.

Setting:

Urban hospital.

Patients:

Neonates exposed to a case of congenital tuberculosis.

Interventions:

Exposure to tuberculosis was treated with isoniazid. Purified protein derivative tests were placed at base-line and 3 to 4 months after exposure. Chest radiographs were performed if clinically indicated.

Results:

Congenital tuberculosis was diagnosed in our patient at 21 days of age during a prolonged hospital course. After initiation of anti-tuberculous medications, the patient gradually recovered from his illness. While he was treated in the NICU, there were 37 potentially exposed infants. Of these, 36 were administered tuberculin skin tests (average age, 1.7 months), all of which were read as 0 mm of induration. Of those 37, 35 began prophylaxis with isoniazid, and 30 were able to complete treatment with a minimum of 3 months of isoniazid therapy. Of those 30, two infants received 6 months of therapy. Additionally, 29 of the 37 infants had chest radiographs, none of which showed suspicious infiltrates or adenopathy. Finally, 30 of the 36 infants had repeat tuberculin skin tests at 3 months, all of which were read as 0 mm of induration (average age, 3.7 months).

Conclusion:

Congenital tuberculosis is an uncommon disease that requires early diagnosis for successful therapy and vigilant follow-up of potential exposures in the NICU. (Infect Control Hosp Epidemiol 2002;23:573-579).
Tuberculin Skin Testing Among Healthcare Workers in the University of Malaya Medical Centre, Kuala Lumpur, Malaysia
Authors: Lian-HuatTan  , Kamarulzaman Adeeba , Iiam Chong-Kin , Lee Toong-Chow
Published: February 2006

Objectives:

To determine the occupational risk of Mycobacterium tuberculosis infection among healthcare workers (HCWs) and to examine the utility of tuberculin skin testing in a developing country with a high prevalence of bacille Calmette-Guerin vaccination.

Design:

Tuberculin skin test (TST) survey.

Setting:

A tertiary-care referral center and a teaching hospital in Kuala Lumpur, Malaysia.

Participants:

HCWs from medical, surgical, and orthopedic wards.

Intervention:

Tuberculin purified protein derivative RT-23 (State Serum Institute, Copenhagen, Denmark) was used for the TST (Mantoux method).

Results:

One hundred thirty-seven (52.1%) and 69 (26.2%) of the HCWs tested had indurations of 10 mm or greater and 15 mm or greater, respectively. Medical ward HCWs were at significantly higher risk of a positive TST reaction than were surgical or orthopedic ward HCWs (odds ratio, 2.18; 95% confidence interval, 1.33 to 3.57; P = .002 for TST positivity at 10 mm or greater) (odds ratio, 2.61; 95% confidence interval, 1.44 to 4.70; P = .002 for TST positivity at 15 mm or greater). A previous TST was a significant risk factor for a positive TST reaction at either 10 mm or greater or 15 mm or greater, but a duration of employment of more than 1 year and being a nurse were only significantly associated with a positive TST reaction at a cut-off point of 15 mm or greater.

Conclusions:

HCWs at the University of Malaya Medical Centre had an increased risk for M. tuberculosis infection that was significantly associated with the level of occupational tuberculosis exposure. A TST cut-off point of 15 mm or greater may correlate better with M. tuberculosis infection than a cut-off point of 10 mm or greater in settings with a high prevalence of bacille Calmette-Guerin vaccination (Infect Control Hosp Epidemiol 2002;23:584-590).
Tuberculin Skin Test Conversion Among Medical Students at a Teaching Hospital in Rio de Janeiro, Brazil
Authors: Silva Vania M. C. , Cunha Antonio Jose Ledo A. , Kritski Afranio L.
Published: February 2006

Objective:

To describe the cumulative incidence of and risk factors for tuberculosis (TB) infection among medical students.

Design:

In 1999, a cohort study of medical students with negative results (induration < 10 mm) on tuberculin skin test (TST) was performed. Students who had undergone two-step testing in 1998 were retested.

Settings:

University and teaching hospital and referral center for TB and acquired immunodeficiency syndrome, and the Health Sciences Building of the Medical School of the Federal University of Rio de Janeiro, Brazil.

Participants:

A sample of 618 consecutive medical students with negative TST results who had been tested 12 months before were approached. Information about sociodemographic characteristics, bacille Calmette-Guérin vaccination history, and potential exposures to TB was obtained using a standardized questionnaire. Four hundred fourteen (67%) students completed the study. Students were at two different levels of their training programs (juniors = no contact with patients; seniors = intensive contact with patients).

Results:

Of 414 participants, 16 (3.9%; 95% confidence interval, 1.06% to 12.1%) had converted to a positive reaction after 1 year. In a multivariate logistic regression analysis, higher level of clinical training was confirmed to be an independent factor associated with TST conversion (odds ratio, 4.77; 95% confidence interval, 1.01 to 22.46; P = .048).

Conclusion:

Senior medical students are at increased risk of Mycobacterium tuberculosis infection in this setting. Therefore, a program of routine tuberculin skin testing and specific TB infection control guidelines are needed for this population (Infect Control Hosp Epidemiol 2002;23:591-594).
Failure to Implement Respiratory Isolation: Why Does it Happen?
Authors: Iwata Kentaro , Smith Barbara A. , Santos Eloisa , Polsky Bruce , Sordillo Emilia M.
Published: February 2006

Background:

Respiratory isolation for 90% of individuals with acid-fast bacillus (AFB)-smear–positive tuberculosis (TB) is a recommended performance indicator in recent Infectious Diseases Society of America and Centers for Disease Control and Prevention guidelines. However, compliance with respiratory isolation reported from multiple centers in the United States and Europe falls short of that goal.

Objective:

To identify missed clues in TB patients who are not appropriately isolated.

Design:

Retrospective survey.

Setting:

A 900-bed voluntary hospital.

Patients:

All patients with AFB-smear–positive TB admitted between January 1995 and December 1999 who were not appropriately isolated.

Results:

There were 173 TB cases admitted, including 106 with pulmonary TB. AFB smears were positive in 82 cases; 24 (29%) of these were not appropriately isolated. During the study period, the number of TB cases declined, but the proportion of appropriately isolated patients did not change. Most isolation failure cases were men (median age, 45.5 years); 21 of these patients were black, 2 were Hispanic white, and 1 was Asian, but none was non-Hispanic white. All isolation failure cases had at least one characteristic predictive of TB that could have been elicited at admission (eg, abnormal chest radiograph findings consistent with TB, fever, weight loss, a history of TB, a positive result on tuberculin skin test, hemoptysis, and human immunodeficiency virus infection).

Conclusion:

Consistent with experiences at other hospitals, we found that the rate of isolation failure remained unchanged despite an overall decline in TB cases. In our experience, almost all isolation failures could be avoided by careful review of the history, physical examination, and chest radiograph for characteristics classically considered predictive of TB. (Infect Control Hosp Epidemiol 2002;23:595-599).
Utility of Zanamivir for Chemoprophylaxis of Concomitant Influenza A and B in a Complex Continuing Care Population
Authors: Hirji Z. , O'Grady S. , Bonham J. , Mak M. , Takata-Shewchuk J. , Hawkins K. , Gardam M. , Law L. , Mazzulli T. , Conly J.
Published: February 2006

Objective:

To describe compliance with and the safety and prophylactic efficacy of zanamivir among patients at risk of developing influenza-related complications after exposure to both influenza A and B viruses.

Design:

Nonrandomized trial using both historical and contemporaneous controls from ward populations within the same facility.

Setting:

A 547-bed urban hospital providing complex continuing care and rehabilitation.

Patients:

Fifty patients on a single ward concomitantly exposed to both influenza A and B during an influenza outbreak.

Interventions:

All patients were screened for symptoms of influenza and nasopharyngeal swabs were sent for viral culture prior to treatment (two oral inhalations [2 × 5 mg] twice daily for 5 days) or prophylaxis (two oral inhalations [2 × 5 mg] once daily for 14 days) with zanamivir. Patient symptoms, compliance, and drug tolerance were monitored daily. Demographic data, comorbidities, vaccination status, and functional status (Katz score) were collected for all patients.

Results:

The mean age of the patients was 70.6 years (standard deviation, ± 16.4 years). Ninety-four percent had two or more comorbidities, 71% were dependent in two or more activities of daily living, 63% had been vaccinated for influenza, and 82% had received amantadine. Zanamivir was well tolerated, with 93% of the patients completing their course. The efficacy for preventing symptomatic infection was 82% and 91% (95% confidence interval, 62% to 98%) based on historical and contemporaneous controls, respectively.

Conclusion:

These data suggest that zanamivir can be used safely and effectively as a prophylactic agent in the management of influenza outbreaks in a complex continuing care population with multiple comorbidities. (Infect Control Hosp Epidem 2002;23:604-608).
Health Behavior Associated With Influenza Vaccination Among Healthcare Workers in Long-Term-Care Facilities
Authors: Manuel D. G. , Henry B. , Hockin J. , Naus M.
Published: February 2006

Objective:

To investigate the health behavior associated with influenza vaccination among healthcare workers (HCWs) in long-term–care facilities.

Design:

A cross-sectional, self-administered survey of HCWs, augmented with focus groups to further examine attitudes toward influenza vaccination.

Setting:

Two long-term–care facilities participated in the survey. The focus groups were held at one of the two facilities.

Participants:

All HCWs were invited to participate in the survey and all nonmanagerial staff members were invited to participate in the focus groups. The response rate for the survey was 58% (231 of 401).

Results:

Vaccinated HCWs had a more positive attitude toward influenza vaccination and a greater belief that the vaccine is effective. This was not accompanied by differences in vaccine knowledge or values of potential preventive outcomes. Nonvaccinated respondents were more likely to believe that other preventive measures, such as washing hands, taking vitamins and supplements, eating a nutritious diet, exercising, and taking homeopathic or naturopathic medications, were more effective than vaccination. Additional findings from the focus groups suggest that HCWs believe that the main purpose of influenza vaccination programs is to protect residents' health at the expense, potential harm, and burden of responsibility of the staff.

Conclusions:

This study identifies challenges to and opportunities for improving vaccination rates among HCWs. A message that emphasizes the health benefits of vaccination to staff members, such as including vaccination as part of a staff “wellness” program, may improve the credibility of influenza immunization programs and coverage rates.(Infect Control Hosp Epidemiol 2002;23:609-614).
Disruption of Services in an Internal Medicine Unit Due to a Nosocomial Influenza Outbreak
Authors: Sartor Catherine , Zandotti Christine , Romain Fanny , Jacomo Véronique , Simon Sophie , Atlan-Gepner Catherine , Sambuc Roland , Vialettes Bernard , Drancourt Michel
Published: February 2006

Objective:

To describe a nosocomial influenza A out-break, how it was managed, what impact it had on subsequent delivery of health care, and the additional charges attributable to it.

Design:

Prospective cohort study and microbiological investigation.

Setting:

One internal medicine unit in an acute care, university-affiliated hospital.

Participants:

Twenty-three patients and 22 staff members from February 28 to March 6,1999.

Results:

Attack rates were 41% (9 of 22) among patients and 23% (5 of 22) among staff members, with 3 of 14 cases being classified as “certain”. The influenza virus isolates were typed as A/SYDNEY/5/97 (H3N2). The index case was a patient who shared a room with the first nosocomial case. Vaccination rates for influenza virus were 43% (10 of 23) among patients and 36% (8 of 22) among staff members. The outbreak resulted in staff members' taking 14 person-days of sick leave. Furthermore, 8 scheduled admissions were postponed and all emergency admissions were suspended for 11 days. Hospital charges attributable to the influenza outbreak totaled $34,179 and the average extra charge per infected patient was $3,798.

Conclusions:

Nosocomial influenza outbreaks increase charges and alter the quality of care delivered in acute care settings. Strategies for their prevention need to be evaluated in acute care settings. (Infect Control Hosp Epidemiol 2002;23:615-619).