148 research outputs found
Hox en Provence
In the nearly 25 years since the cloning of the first Hox genes, the broad brushstrokes of their functions in axial patterning have become familiar motifs in developmental biology. The October 2007 Fondation des Treilles workshop on âHox Genes in Development and Evolutionâ in Les Treilles, France, highlighted some of the finer details regarding the function of these genes in shaping animal morphology
Active Site Mutations Change the Cleavage Specificity of Neprilysin
Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid ÎČ1â40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid Ă1â40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential
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Mobile assistive technologies for the visually impaired
There are around 285 million visually impaired people worldwide, and around 370,000 people are registered as blind or partially sighted in the UK. Ongoing advances in information technology (IT) are increasing the scope for IT-based mobile assistive technologies to facilitate the independence, safety, and improved quality of life of the visually impaired. Research is being directed at making mobile phones and other handheld devices accessible via our haptic (touch) and audio sensory channels. We review research and innovation within the field of mobile assistive technology for the visually impaired and, in so doing, highlight the need for successful collaboration between clinical expertise, computer science, and domain users to realize fully the potential benefits of such technologies. We initially reflect on research that has been conducted to make mobile phones more accessible to people with vision loss. We then discuss innovative assistive applications designed for the visually impaired that are either delivered via mainstream devices and can be used while in motion (e.g., mobile phones) or are embedded within an environment that may be in motion (e.g., public transport) or within which the user may be in motion (e.g., smart homes)
Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course
Table of contents
O1 Tumour heterogeneity: what does it mean?
Dow-Mu Koh
O2 Skeletal sequelae in adult survivors of childhood cancer
Sue Creviston Kaste
O3 Locoregional effects of breast cancer treatment
Sarah J Vinnicombe
O4 Imaging of cancer therapy-induced CNS toxicity
Giovanni Morana, Andrea Rossi
O5 Screening for lung cancer
Christian J. Herold
O6Risk stratification of lung nodules
Theresa C. McLoud
O7 PET imaging of pulmonary nodules
Kirk A Frey
O8 Transarterial tumour therapy
Bernhard Gebauer
O9 Interventional radiology in paediatric oncology
Derek Roebuck
O10 Image guided prostate interventions
Jurgen J. FĂŒtterer
O11 Imaging cancer predisposition syndromes
Alexander J. Towbin
O12Chest and chest wall masses
Thierry AG Huisman
O13 Abdominal masses: good or bad?
Anne MJB Smets
O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management
Giovanni Morana
O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC
Jeong Min Lee
O16 Opportunities and challenges in imaging metastatic disease
Hersh Chandarana
O17 Diagnosis, treatment monitoring, and follow-up of lymphoma
Marius E. Mayerhoefer, Markus Raderer, Alexander Haug
O18 Managing high-risk and advanced prostate cancer
Matthias Eiber
O19 Immunotherapy: imaging challenges
Bernhard Gebauer
O20 RECIST and RECIST 1.1
Andrea Rockall
O21 Challenges of RECIST in oncology imaging basics for the trainee and novice
Aslam Sohaib
O22 Lymphoma: PET for interim and end of treatment response assessment: a usersâ guide to the Deauville Score
Victoria S Warbey
O23 Available resources
Hebert Alberto Vargas
O24 ICIS e-portal and the online learning community
Dow-Mu Koh
O25 Benign lesions that mimic pancreatic cancer
Jay P Heiken
O26 Staging and reporting pancreatic malignancies
Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza
O27 Intraductal papillary mucinous neoplasm
Giovanni Morana
O28 Cystic pancreatic tumours
Mirko DâOnofrio
O29 Diffusion-weighted imaging of head and neck tumours
Harriet C. Thoeny
O30 Radiation injury in the head and neck
Ann D King
O31 PET/MR of paediatric brain tumours
Giovanni Morana, Arnoldo Piccardo, Maria Luisa GarrĂš, Andrea Rossi
O32 Structured reporting and beyond
Hebert Alberto Vargas
O33 Massachusetts General Hospital experience with structured reporting
Theresa C. McLoud
O34 The oncologistâs perspective: what the oncologist needs to know
Nick Reed
O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology
Carlos Rodriguez-Galindo
O36 Multiparametric imaging of renal cancers
Hersh Chandarana
O37 Linking imaging features of renal disease and their impact on management strategies
Hebert Alberto Vargas
O38 Adrenals, retroperitoneum and peritoneum
Isaac R Francis, Ashish P Wasnik
O39 Lung and pleura
Stefan Diederich
O40 Advances in MRI
Jurgen J. FĂŒtterer
O41 Advances in molecular imaging
Wim J.G. Oyen
O42 Incorporating advanced imaging, impact on treatment selection and patient outcome
Cheng Lee Chaw, Nicholas van As
S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer
Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye
S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases
R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A DâHoore, A Wolthuis, V Vandecaveye
S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer.
P. Pricolo ([email protected]), S. Alessi, P. Summers, E. Tagliabue, G. Petralia
S4 Generating evidence for clinical benefit of PET/CT â are management studies sufficient as surrogate for patient outcome?
C. Pfannenberg, B. GĂŒckel, SC SchĂŒle, AC MĂŒller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus
S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET
GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh
S6 Accuracy of suspicious breast imagingâcan we tell the patient?
S Seth, R Burgul, A Seth
S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response
S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe
S8 Diagnostic yield of CT IVU in haematuria screening
F. Arfeen, T. Campion, E. Goldstraw
S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results
DâOnofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R
S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients
M. Uhrig, D. Simons, H. Schlemmer
S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb?
Kate Downey
S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield.
S Murdoch, AS Al-adhami, S Viswanathan
P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations
S Smith, P Jennings, D Bowers, R Soomal
P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease
S Smith, P Jennings, D Bowers, R Soomal
P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges
TM Mutala, AO Odhiambo, N Harish
P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer
P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia
P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015
M. Hall, M. Sproule, S. Sheridan
P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm
KY Thein, CH Tan, YL Thian, CM Ho
P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience
S De Luca, C Carrera, V Blanchet, L AlarcĂłn, E Eyheremnedy
P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25Â years experience
B K Choudhury, K Bujarbarua, G Barman
P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1
GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey
P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions
L Potti, B Kaye, A Beattie, K Dutton
P11 Can we reduce prevalent recall rate in breast screening?
AA Seth, F Constantinidis, H Dobson
P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV)
AA Seth ([email protected]), F Constantinidis, H Dobson
P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT
R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas
P14 A one-stop lymphoma biopsy service â is it possible?
S Bhuva, CA Johnson, M Subesinghe, N Taylor
P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017)
LE Quint, RM Reddy, GP Kalemkerian
P16 Cancer immunotherapy: a review of adequate imaging assessment
G GonzĂĄlez Zapico, E Gainza Jauregui, R Ălvarez Francisco, S Ibåñez Alonso, I Tavera Bahillo, L MĂșgica Ălvarez
P17 Succinate dehydrogenase mutations and their associated tumours
O Francies, R Wheeler, L Childs, A Adams, A Sahdev
P18 Initial experience in the usefulness of dual energy technique in the abdomen
SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy
P19 Recognising the serious complication of Richterâs transformation in CLL patients
C Stove, M Digby
P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips
M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy
P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients
D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein
P22 Pitfalls in oncology CT reporting. A pictorial review
R Rueben, S Viswanathan
P23 Imaging of perineural extension in head and neck tumours
B Nazir, TH Teo, JB Khoo
P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer
K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins
P25 When cancer canât wait! A pictorial review of oncological emergencies
K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua
P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation
D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh
P27 Gynaecological cancers in pregnancy: a review of imaging
CA Johnson, J Lee
P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart
JA Goodfellow, AS Al-adhami, S Viswanathan
P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy
R Bradley
P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience
R Bradley
P31 Radiological assessment of the post-chemotherapy liver
A Yong, S Jenkins, G Joseph
P32 Skeletal staging with MRI in breast cancer â what the radiologist needs to know
S Bhuva, K Partington
P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease
CA Johnson, S Bhuva, M Subesinghe, N Taylor
P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools.
C Carrera, A Zanfardini, S De Luca, L AlarcĂłn, V Blanchet, EP Eyheremendy
P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test?
K Cavanagh, E Lauhttp://deepblue.lib.umich.edu/bitstream/2027.42/134651/1/40644_2016_Article_79.pd
Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD
Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10â392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group
Clinical, physiologic, and radiographic factors contributing to development of hypoxemia in moderate to severe COPD:a cohort study
Background: Hypoxemia is a major complication of COPD and is a strong predictor of mortality. We previously identified independent risk factors for the presence of resting hypoxemia in the COPDGene cohort. However, little is known about characteristics that predict onset of resting hypoxemia in patients who are normoxic at baseline. We hypothesized that a combination of clinical, physiologic, and radiographic characteristics would predict development of resting hypoxemia after 5-years of follow-up in participants with moderate to severe COPD Methods: We analyzed 678 participants with moderate-to-severe COPD recruited into the COPDGene cohort who completed baseline and 5-year follow-up visits and who were normoxic by pulse oximetry at baseline. Development of resting hypoxemia was defined as an oxygen saturation â€88% on ambient air at rest during follow-up. Demographic and clinical characteristics, lung function, and radiographic indices were analyzed with logistic regression models to identify predictors of the development of hypoxemia. Results: Forty-six participants (7%) developed resting hypoxemia at follow-up. Enrollment at Denver (OR 8.30, 95%CI 3.05â22.6), lower baseline oxygen saturation (OR 0.70, 95%CI 0.58â0.85), self-reported heart failure (OR 6.92, 95%CI 1.56â30.6), pulmonary artery (PA) enlargement on computed tomography (OR 2.81, 95%CI 1.17â6.74), and prior severe COPD exacerbation (OR 3.31, 95%CI 1.38â7.90) were independently associated with development of resting hypoxemia. Participants who developed hypoxemia had greater decline in 6-min walk distance and greater 5-year decline in quality of life compared to those who remained normoxic at follow-up. Conclusions: Development of clinically significant hypoxemia over a 5-year span is associated with comorbid heart failure, PA enlargement and severe COPD exacerbation. Further studies are needed to determine if treatments targeting these factors can prevent new onset hypoxemia. Trial registration COPDGene is registered at ClinicalTrials.gov: NCT00608764 (Registration Date: January 28, 2008) Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0331-0) contains supplementary material, which is available to authorized users
Injectable local anaesthetic agents for dental anaesthesia
Background: Pain during dental treatment, which is a common fear of patients, can be controlled successfully by local anaesthetic. Several different local anaesthetic formulations and techniques are available to dentists. / Objectives: Our primary objectives were to compare the success of anaesthesia, the speed of onset and duration of anaesthesia, and systemic and local adverse effects amongst different local anaesthetic formulations for dental anaesthesia. We define success of anaesthesia as absence of pain during a dental procedure, or a negative response to electric pulp testing or other simulated scenario tests. We define dental anaesthesia as anaesthesia given at the time of any dental intervention.
Our secondary objective was to report on patients' experience of the procedures carried out. / Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2018, Issue 1), MEDLINE (OVID SP), Embase, CINAHL PLUS, WEB OF SCIENCE, and other resources up to 31 January 2018. Other resources included trial registries, handsearched journals, conference proceedings, bibliographies/reference lists, and unpublished research. / Selection criteria: We included randomized controlled trials (RCTs) testing different formulations of local anaesthetic used for clinical procedures or simulated scenarios. Studies could apply a parallel or crossâover design. / Data collection and analysis: We used standard Cochrane methodological approaches for data collection and analysis. / Main results: We included 123 studies (19,223 participants) in the review. We pooled data from 68 studies (6615 participants) for metaâanalysis, yielding 23 comparisons of local anaesthetic and 57 outcomes with 14 different formulations. Only 10 outcomes from eight comparisons involved clinical testing.
We assessed the included studies as having low risk of bias in most domains. Seventyâthree studies had at least one domain with unclear risk of bias. Fifteen studies had at least one domain with high risk of bias due to inadequate sequence generation, allocation concealment, masking of local anaesthetic cartridges for administrators or outcome assessors, or participant dropout or exclusion.
We reported results for the eight most important comparisons. / Success of anaesthesia: When the success of anaesthesia in posterior teeth with irreversible pulpitis requiring root canal treatment is tested, 4% articaine, 1:100,000 epinephrine, may be superior to 2% lidocaine, 1:100,000 epinephrine (31% with 2% lidocaine vs 49% with 4% articaine; risk ratio (RR) 1.60, 95% confidence interval (CI) 1.10 to 2.32; 4 parallel studies; 203 participants; lowâquality evidence).
When the success of anaesthesia for teeth/dental tissues requiring surgical procedures and surgical procedures/periodontal treatment, respectively, was tested, 3% prilocaine, 0.03 IU felypressin (66% with 3% prilocaine vs 76% with 2% lidocaine; RR 0.86, 95% CI 0.79 to 0.95; 2 parallel studies; 907 participants; moderateâquality evidence), and 4% prilocaine plain (71% with 4% prilocaine vs 83% with 2% lidocaine; RR 0.86, 95% CI 0.75 to 0.99; 2 parallel studies; 228 participants; lowâquality evidence) were inferior to 2% lidocaine, 1:100,000 epinephrine.
Comparative effects of 4% articaine, 1:100,000 epinephrine and 4% articaine, 1:200,000 epinephrine on success of anaesthesia for teeth/dental tissues requiring surgical procedures are uncertain (RR 0.85, 95% CI 0.71 to 1.02; 3 parallel studies; 930 participants; very lowâquality evidence).
Comparative effects of 0.5% bupivacaine, 1:200,000 epinephrine and both 4% articaine, 1:200,000 epinephrine (odds ratio (OR) 0.87, 95% CI 0.27 to 2.83; 2 crossâover studies; 37 participants; lowâquality evidence) and 2% lidocaine, 1:100,000 epinephrine (OR 0.58, 95% CI 0.07 to 5.12; 2 crossâover studies; 31 participants; lowâquality evidence) on success of anaesthesia for teeth requiring extraction are uncertain.
Comparative effects of 2% mepivacaine, 1:100,000 epinephrine and both 4% articaine, 1:100,000 epinephrine (OR 3.82, 95% CI 0.61 to 23.82; 1 parallel and 1 crossâover study; 110 participants; lowâquality evidence) and 2% lidocaine, 1:100,000 epinephrine (RR 1.16, 95% CI 0.25 to 5.45; 2 parallel studies; 68 participants; lowâquality evidence) on success of anaesthesia for teeth requiring extraction and teeth with irreversible pulpitis requiring endodontic access and instrumentation, respectively, are uncertain.
For remaining outcomes, assessing success of dental local anaesthesia via metaâanalyses was not possible. / Onset and duration of anaesthesia: For comparisons assessing onset and duration, no clinical studies met our outcome definitions.
Adverse effects (continuous pain measured on 170âmm HeftâParker visual analogue scale (VAS))
Differences in postâinjection pain between 4% articaine, 1:100,000 epinephrine and 2% lidocaine, 1:100,000 epinephrine are small, as measured on a VAS (mean difference (MD) 4.74 mm, 95% CI â1.98 to 11.46 mm; 3 crossâover studies; 314 interventions; moderateâquality evidence). Lidocaine probably resulted in slightly less postâinjection pain than articaine (MD 6.41 mm, 95% CI 1.01 to 11.80 mm; 3 crossâover studies; 309 interventions; moderateâquality evidence) on the same VAS.
For remaining comparisons assessing local and systemic adverse effects, metaâanalyses were not possible. Other adverse effects were rare and minor. / Patients' experience: Patients' experience of procedures was not assessed owing to lack of data. / Authors' conclusions: For success (absence of pain), lowâquality evidence suggests that 4% articaine, 1:100,000 epinephrine was superior to 2% lidocaine, 1:100,000 epinephrine for root treating of posterior teeth with irreversible pulpitis, and 2% lidocaine, 1:100,000 epinephrine was superior to 4% prilocaine plain when surgical procedures/periodontal treatment was provided. Moderateâquality evidence shows that 2% lidocaine, 1:100,000 epinephrine was superior to 3% prilocaine, 0.03 IU felypressin when surgical procedures were performed.
Adverse events were rare. Moderateâquality evidence shows no difference in pain on injection when 4% articaine, 1:100,000 epinephrine and 2% lidocaine, 1:100,000 epinephrine were compared, although lidocaine resulted in slightly less pain following injection.
Many outcomes tested our primary objectives in simulated scenarios, although clinical alternatives may not be possible.
Further studies are needed to increase the strength of the evidence. These studies should be clearly reported, have low risk of bias with adequate sample size, and provide data in a format that will allow metaâanalysis. Once assessed, results of the 34 âStudies awaiting classification (full text unavailable)â may alter the conclusions of the review
Caenorhabditis elegans apoptosis
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2002.Includes bibliographical references.The process of programmed cell death is important in the development and homeostasis of multicellular organisms. The conserved morphological events of this process have been termed apoptosis. The molecular mechanisms of apoptosis execution are also conserved. We have investigated the behavior of these shared components during programmed cell death in the nematode Caenorhabditis elegans. We have found that the CED-9 protein, an anti-apoptotic member of the Bcl-2 family of apoptotic regulators, is required for the sequestering of the CED-4 cell-death activator to mitochondria. In the absence of CED-9 in C. elegans embryos, we found that CED-4 protein translocates to the nuclear membrane. In addition, inducing excess programmed cell death by expression of the EGL-1 cell-death activator triggers the translocation of CED-4 from mitochondria to the nuclear membrane. We performed a genetic screen for mutations that trigger programmed cell death in ced-9 gain-of-function animals where cell death is blocked. We identified a mutation in cup-5, the C. elegans homolog of the human mucolipidosis type IV gene, which is mutated in a lysosomal storage disorder. We found that cup-5 is required for viability and that excess lysosomes accumulate in cup-5 mutants. In addition, cup--5 mutants contain excess programmed cell deaths, suggesting that apoptosis may play a role in the pathology of mucolipidosis type IV.by Bradley Michael Hersh.Ph.D
Rational use of rubella vaccine for prevention of congenital rubella syndrome in the Americas
Rubella is a viral disease with minor morbidity and few complications unless it is contracted by a pregnant woman. Rubella infection during the first trimester of pregnancy often leads to fetal death or severe congenital defects (congenital rubella syndrome, CRS). Rubella remains endemic in many countries of Latin America and the Caribbean. It has been estimated that 20000 or more infants are perhaps born with CRS each year in Latin American and Caribbean countries. While the inclusion of rubella vaccination into routine childhood immunization will decrease rubella virus circulation among young children, it will not have immediate impact on the transmission of rubella among adults or the occurrence of CRS. A one-time mass campaign targeting both males and females 5 to 39 years of age with measles-mumps-rubella or measles-rubella vaccine followed by the use of measles-mumps-rubella vaccine in routine early childhood vaccination will prevent and control both rubella and CRS promptly. In April 1988, the Ministers of Health of the English-speaking Caribbean targeted rubella for elimination by the end of the year 2000 using the vaccination strategy outlined above. The rubella elimination experience of these countries will provide useful information for the eventual elimination of rubella virus from the Americas.<br>La rubĂ©ola es una enfermedad vĂrica que produce poca morbilidad y pocas complicaciones, a no ser que la contraiga una mujer embarazada. La infecciĂłn con rubĂ©ola durante el primer trimestre del embarazo a menudo termina en muerte fetal o en deformidades congĂ©nitas graves (sĂndrome de anomalĂas congĂ©nitas por rubĂ©ola, o SCR). La rubĂ©ola sigue siendo endĂ©mica en muchos paĂses de AmĂ©rica Latina y el Caribe. Se estima que quizĂĄ 20 000 niños o mĂĄs nacen cada año con SCR en paĂses latinoamericanos y caribeños. Si bien la adiciĂłn de la vacuna contra la rubĂ©ola a los programas de inmunizaciĂłn infantil de rutina disminuirĂĄ la circulaciĂłn del virus entre los niños pequeños, no tendrĂĄ un impacto inmediato sobre la transmisiĂłn de la rubĂ©ola entre los adultos o sobre la frecuencia de SCR. Una campaña Ășnica dirigida a toda la poblaciĂłn de hombres y mujeres de 5 a 39 años de edad en que se aplique la vacuna triple contra el sarampiĂłn, la parotiditis y la rubĂ©ola, o la vacuna doble contra el sarampiĂłn y la rubĂ©ola seguida de la vacuna triple como parte de la inmunizaciĂłn rutinaria de niños pequeños servirĂĄ para controlar y prevenir de manera inmediata tanto la rubĂ©ola como el SCR. En abril de 1988, los Ministros de Salud de paĂses del Caribe angloparlante establecieron la meta de eliminar la rubĂ©ola para fines del año 2000 mediante la aplicaciĂłn de la estrategia de vacunaciĂłn aquĂ descrita. La experiencia que han tenido estos paĂses en sus actividades de eliminaciĂłn de la rubĂ©ola serĂĄ fuente de informaciĂłn provechosa para la eliminaciĂłn futura del virus de la rubĂ©ola de todo el territorio americano
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