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At least 865 records · Page 48Linked to original sources
PubMed2006

Expression of two cell wall proteins during the intracellular development of Encephalitozoon cuniculi: an immunocytochemical and in situ hybridization study with ultrathin frozen sections.

The microsporidian Encephalitozoon cuniculi is an obligate intracellular parasite that develops asynchronously inside parasitophorous vacuoles. Spore differentiation involves the construction of a cell wall commonly divided into an outer layer (exospore) and a thicker, chitin-rich inner layer (endospore). The developmental patterns of protein deposition and mRNA expression for 2 different spore wall proteins were studied using immunocytochemical and in situ hybridization procedures with ultrathin frozen sections. The onset of deposition of an exospore-destined protein (SWP1) correlated with the formation of lamellar protuberances during meront-to-sporont conversion. No evidence for a release of SWP1 towards the parasitophorous vacuole lumen was obtained. An endospore-destined protein (EnP1) was detected early on the plasma membrane of meronts prior to extensive accumulation within the chitin-rich layer of sporoblasts. swp1 mRNA was preferentially synthesized in early sporogony while enp1 mRNA was transcribed during merogony and a large part of sporogony. The level of both mRNAs was reduced in mature spores. Considering the availability of the E. cuniculi genome sequence, the application of nucleic and/or protein probes to cryosections should facilitate the screening of various genes for stage-specific expression during microsporidian development.

Animals↗
PubMedDate not supplied

Use and analysis of field triage criteria for mass gatherings.

INTRODUCTION: Mass gatherings may result in an acute increase in the number of people seeking medical care potentially causing undue stress to local emergency medical services (EMS) and hospitals. Often, temporary medical facilities are established within the mass gathering venue. Emergency Medical Services providers encountering patients in the field should be equipped with effective protocols to determine transport destination (venue facility vs. hospital). HYPOTHESIS: Paramedics are capable of appropriately using triage criteria written specifically for a particular mass gathering. The use of triage criteria, when applied correctly, decreases over-triage to the venue facility and undertriage to the hospital. METHODS: Paramedics triaged patients at a mass gathering to a temporary venue facility or to a single emergency department using criteria specific for the event. Cases were reviewed to determine if the patients transported went to an appropriate facility and if the triage criteria were applied appropriately. RESULTS: Transport destination was consistent with that dictated by the criteria for 78% of cases. Analysis of these cases shows that the criteria had a sensitivity of 100% (95% CI = 58-100%) and a specificity of 90% (95% CI = 73-98%) for predicting which patients needed hospital services and which could be cared for safely in the temporary clinic setting. CONCLUSIONS: Triage by paramedics at the point of patient contact may reduce transporting of patients to hospitals unnecessarily. Patients in need of hospital services were identified. Point-of-contact triage should be applied in mass gatherings.

Adolescent↗
PubMedDate not supplied

Complication rates for the esophageal obturator airway and endotracheal tube in the prehospital setting.

PURPOSE: The purpose of this study was to determine the complication rates associated with the use of the endotracheal tube (ET) and the use of the esophageal obturator airway/esophageal gastric tube airway (EOA/EGTA) during the treatment of patients with prehospital cardiac arrest. METHODS: A descriptive, quasi-experimental study of 509 consecutive adults, cardiac arrest patients was conducted. Patients were examined prospectively for airway intervention type and complications. Some patients were examined at their final destinations (field, morgue, funeral home), while other patients were examined by EMS providers in the field when airway adjuncts were switched. Also, airways were evaluated for complications by emergency physicians at destination emergency departments. RESULTS: The airway in use at the time of examination was the esophageal obturator airway (EOA) or esophageal gastric tube airway (EGTA) in 208 patients (40.1%); the ET (endotracheal tube) in 232 patients (45.6%); and an oral or nasopharyngeal airway in 47 patients (9.2%). Twenty-two patients (4.3%) had both an EOA/EGTA and an ET tube in place at the time of the examination. The survival rates were similar between the EOA/EGTA and the ET groups (28% and 32%, respectively). The complication rates overall also were similar, but the serious or potentially lethal complication rate was 3.3 times more common with the use of the EOA/EGTA than with the ET tube (8.7% versus 2.6%, respectively). CONCLUSIONS: The complication rate for the EOA/EGTA is unacceptably high, and careful thought must be given to its continued use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

One axon, many kinesins: What's the logic?

A large number of membrane-bounded organelles, protein complexes, and mRNAs are transported along microtubules to different locations within the neuronal axon. Axonal transport in the anterograde direction is carried out by members of a superfamily of specialized motor proteins, the kinesins. All kinesins contain a conserved motor domain that hydrolyses ATP to generate movement along microtubules. Regions outside the motor domain are responsible for cargo binding and regulation of motor activity. Present in a soluble, inactive form in the cytoplasm, kinesins are activated upon cargo binding. Selective targeting of different types of kinesin motors to specific cargoes is directed by amino acid sequences situated in their variable tails. Cargo proteins with specific function at their destination, bind directly to specific kinesins for transport. Whereas most kinesins move to microtubule plus-ends, a small number of them move to microtubule minus-ends, and may participate in retrograde axonal transport. Axonal transport by kinesins has a logic: Fully assembled, multisubunit, functional complexes (e.g., ion channel complexes, signaling complexes, RNA-protein complexes) are transported to their destination by kinesin motors that interact transiently (i.e., during transport only) with one of the complexes' subunits.

Animals↗
PubMed2002

Surviving apoptosis.

The concept that cells subjected to chromatin cleavage during apoptosis are destined to die is being challenged. The execution phase of apoptosis is characterized by the activation of effector caspases, such as caspase-3, that cleave key regulatory or structural proteins and in particular activate apoptotic nucleases such as the caspase activated deoxyribonuclease (CAD). It is apparent that caspases of this type may become active both through non-apoptotic processing and potentially within cells that exhibit apoptotic morphology but are subsequently able to survive. In such systems caspase suppressor molecules, the inhibitors of apoptotic proteins or IAP's, may rescue cells from apoptotic nuclease(s) attack initiated by transient caspase activation. The MLL gene is involved in leukemogenic translocations in ALL and AML and is a target of nuclease cleavage during apoptosis. Translocations initiated at the site of apoptotic nuclease attack within MLL have been identified and may offer a model, with clinical relevance, for DNA damage mediated by the apoptosis system in cells destined to survive. The specificity of apoptotic cleavage combined with the potential for recovery from the execution phase of apoptosis suggests a novel and pathogenic role for apoptosis in creating translocations with leukemogenic potential.

Animals↗
PubMed1997

The relationship between developing oligodendrocyte units and maturing axons during myelinogenesis in the anterior medullary velum of neonatal rats.

Myelinogenesis was investigated in whole-mounted anterior medullary vela from rats aged postnatal day (P) 10-12, using double immunofluorescence labelling with Rip and anti-neurofilament 200 (NF200) antibodies, to identify oligodendrocytes and axons, respectively. A number of discrete phases of maturation of oligodendrocyte units were recognised. (1) Promyelinating oligodendrocytes co-expressed Rip and Myelin basic Protein and formed axonal associations, prior to ensheathment. (2) Transitional oligodendrocytes contained both ensheathing and non-ensheating processes. (3) Myelinating oligodendrocytes were established after a period of remodelling (in which non-ensheathing processes were lost), appearing as oligodendrocyte unit morphological phenotypes with a definitive number of incipient myelin sheaths. (4) Maturation of myelinating oligodendrocytes was defined as the establishment of internodal sheath lengths and the redistrubution of myelin basic protein from the cell somata and radial processes into the myelin sheaths only. Myelination was probably related to the maturational state of the axons, since it was initiated when the latter had attained a critical diameter of between approximately 0.2 and 0.4 micron, coincident with the expression of NF200. Oligodendrocyte differentiation and myelination of the AMV were asynchronous and multifocal, and at P10: (1) axons which were destined to be of the largest calibre in the adult AMV were already myelinated by early developing oligodendrocytes, whilst those which were destined to be the smallest calibre in the adult were unmyelinated, but ultimately became ensheathed by late developing oligoendrocytes; (2) axons were sequentially ensheathed by early developing myelinating oligodendrocytes and late developing promyelinating oligodendrocytes; (3) all axons were small calibre; (4) oligodendrocyte units exhibited polymorphism. Thus, the development of oligodendrocyte morphological phenotypes was not related solely to either the physical dimension of axon calibre at the time of ensheathment, nor oligodendrocyte birth dates.

Animals↗
PubMed2005

[Knowledge, attitudes and practices among travellers to tropical and subtropical countries].

Passengers with destinations in developing countries have been interviewed prior to departure on Zurich Airport. A total of 946 questionnaires were evaluated, 337 on travel related malaria prior to visiting an endemic country, 609 on vaccinations. This corresponds to a response rate of 72.3%. Among the respondents 550 (58.1%) had received travel health advice by a doctor. Overall, 25.5% were immunized against hepatitis A. While 70.4% of those who had obtained travel health advice carried medication against malaria, only 31.3% of those without such advice did so. Travel health advice resulted in a significantly increased appreciation of the risk of hepatitis A or malaria at the destination. Considerations on healthy travel should become a cornerstone in travel planning; special risk groups have been identified.

Adolescent↗
PubMed2002

Traveling after heart transplantation.

BACKGROUND: With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines. METHODS: Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed. RESULTS: Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities. CONCLUSIONS: Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.

Adult↗
PubMed2003

PtdIns(3,5)P2 is required for delivery of endocytic cargo into the multivesicular body.

The endocytic pathway transports cargo from the plasma membrane to early endosomes, where certain cargoes are sorted to the late endosome/multivesicular body. Biosynthetic cargo destined for the lysosome is also trafficked through the multivesicular body. Once delivered to the multivesicular body, cargo destined for the interior of the lysosome is selectively sorted into vesicles that bud into the lumen of the multivesicular body. These vesicles are released into the lumen of the lysosome upon the fusion of the multivesicular body and lysosomal limiting membranes. The yeast protein Fab1, which catalyzes the production of phosphatidylinositol (3,5) bisphosphate [PtdIns(3,5)P2], is necessary for proper sorting of biosynthetic cargo in the multivesicular body. Utilizing an endocytosis screen, we isolated a novel allele of FAB1 that contains a point mutation in the lipid kinase domain. Characterization of this allele revealed reduced PtdIns(3,5)P2 production, altered vacuole morphology, and biosynthetic protein sorting defects. We also found that endocytosis of the plasma membrane protein Ste3 is partially blocked downstream of the internalization step, and that delivery of the dye FM4-64 to the vacuole is delayed in fab1 mutants. Additionally, Ste3 is not efficiently sorted into multivesicular body vesicles in fab1 mutants and instead localizes to the vacuolar limiting membrane. These data show that PtdIns(3,5)P2 is necessary for proper trafficking and sorting of endocytic cargo through the late endosome/multivesicular body.

Amino Acid Sequence↗
PubMed1988

Migration of young neurons in adult avian brain.

Neurons are born in the ventricular walls of the vertebrate central nervous system. From there, the young neurons migrate to their final destinations, where differentiation occurs. Neuronal migration has been described during the ontogeny of the avian and mammalian brain. Whereas in mammals most neurogenesis occurs during early development, in the adult avian forebrain wide-spread neurogenesis continues to occur. How do neurons born in adulthood reach their final destination? We report here that small elongated cells, born in the ventricular zone adjacent to the lateral ventricle, differentiate into mature neurons 20-40 days later, after migrating over distances of up to 5 mm. Migration rates are highest (28 micron h-1) when young neurons migrate through regions which are rich in radial glia. The adult vertebrate brain offers unique opportunities for studying factors that regulate neuronal migration, pathfinding and differentiation.

Animals↗
PubMed2001

Involvement of chemokine receptors in breast cancer metastasis.

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Actins↗
PubMed2004

Animal behaviour: geomagnetic map used in sea-turtle navigation.

Migratory animals capable of navigating to a specific destination, and of compensating for an artificial displacement into unfamiliar territory, are thought to have a compass for maintaining their direction of travel and a map sense that enables them to know their location relative to their destination. Compasses are based on environmental cues such as the stars, the Sun, skylight polarization and magnetism, but little is known about the sensory mechanism responsible for the map sense. Here we show that the green sea-turtle (Chelonia mydas) has a map that is at least partly based on geomagnetic cues.

Aging↗
PubMed1994

Temporal profiles of accumulation of amyloid beta/A4 protein precursor in the gerbil after graded ischemic stress.

The neurons that accumulate beta/A4 amyloid protein precursor (APP) after transient cerebral ischemia were characterized by comparing their distribution with those destined to suffer delayed neuronal death or those with induction of 72-kDa heat-shock protein. With immunohistochemistry of APP in gerbil brains, no alterations were detected after ischemia for 2 min and subsequent reperfusion for up to 7 days, whereas after ischemia for 3 min and reperfusion for 48 h, a small number of neurons, intensely immunoreactive for APP, were found to be scattered in the CA1 subfield of the hippocampus and the layer V/VI of the frontoparietal cortex. After reperfusion for 24 h following ischemia for 5 or 15 min, a large number of densely stained neurons appeared in the subiculum, and CA3 subfield of the hippocampus, and layers III and V/VI of the frontoparietal cortex. The majority of these neurons did not undergo delayed neuronal death after reperfusion for 72 h and thereafter. APP and heat-shock protein were upregulated in the same regions, but mostly in distinct neurons. These results indicate that APP accumulates in the neurons marginating the regions destined to die, and the majority of these neurons seem to survive after ischemic insult.

Amyloid beta-Peptides↗
PubMed2003

Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole.

Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles. For example, the yeast class V myosin, Myo2p, moves several organelles to distinct locations during the cell cycle. Thus the movement of each type of Myo2p cargo must be regulated uniquely. Here we report a regulatory mechanism that specifically provides directionality to vacuole movement. The vacuole-specific Myo2p receptor, Vac17p, has a key function in this process. Vac17p binds simultaneously to Myo2p and to Vac8p, a vacuolar membrane protein. The transport complex, Myo2p-Vac17p-Vac8p, moves the vacuole to the bud, and is then disrupted through the degradation of Vac17p. The vacuole is ultimately deposited near the centre of the bud. Removal of a PEST sequence (a potential signal for rapid protein degradation) within Vac17p causes its stabilization and the subsequent 'backward' movement of vacuoles, which mis-targets them to the neck between the mother cell and the bud. Thus the regulated disruption of this transport complex places the vacuole in its proper location. This may be a general mechanism whereby organelles are deposited at their terminal destination.

Amino Acid Motifs↗
PubMed2004

Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons.

Cilia have diverse roles in motility and sensory reception and their dysfunction contributes to cilia-related diseases. Assembly and maintenance of cilia depends on the intraflagellar transport (IFT) of axoneme, membrane, matrix and signalling proteins to appropriate destinations within the organelle. In the current model, these diverse cargo proteins bind to multiple sites on macromolecular IFT particles, which are moved by a single anterograde IFT motor, kinesin-II, from the ciliary base to its distal tip, where cargo-unloading occurs. Here, we describe the observation of fluorescent IFT motors and IFT particles moving along distinct domains within sensory cilia of wild-type and IFT-motor-mutant Caenorhabditis elegans. We show that two anterograde IFT motor holoenzymes, kinesin-II and Osm-3-kinesin, cooperate in a surprising way to control two pathways of IFT that build distinct parts of cilia. Instead of each motor independently moving its own specific cargo to a distinct destination, the two motors function redundantly to transport IFT particles along doublet microtubules adjacent to the transition zone to form the axoneme middle segment. Next, Osm-3-kinesin alone transports IFT particles along the distal singlet microtubules to stabilize the distal segment. Thus, the subtle coordinate activity of these IFT motors creates two sequential transport pathways.

Animals↗
PubMed1997

Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response.

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-points after diagnosis (ie 1, 2-3, 4-6 and 7-12 months) using FR1 and JH primers (fingerprinting with a sensitivity > or =1:5 x 10[3]). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:10[4] and 1:10[5]) were applied to 12 children and 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All patients were followed clinically for > or =24 months. Thirty adults and 16 children presented as newly diagnosed ALL, while the remaining eight patients were analysed in first or subsequent relapse. Patients destined to relapse showed a higher proportion of positive tests (> or =50%), particularly after 1 month, than in the remission group, irrespective of age. Among patients staying in remission, a decrease in MRD-positive tests occurred during the first 12 months in both age groups. However, the proportion of positive tests dropped below 15% at a later stage in adults (4-6 months) than in children (2-3 months). Among children, only patients destined to relapse were MRD positive beyond 1 month, with the exception of only one patient, still positive at 2-3 months in the remission group. The difference in MRD positivity between relapse and remission patients was statistically significant in children (P < 0.03) at any time of testing, but only at 4-6 months in adults (P < 0.01). These data suggest that resolution of MRD in ALL occurs more rapidly in children compared to adults, particularly within the first 6 months. Children and adults, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patients.

Adolescent↗
PubMed1999

Predictive validity of the BRASS index in screening patients with post-discharge problems. Blaylock Risk Assessment Screening Score.

RATIONALE: Discharge planning is a nursing intervention that aims to ensure continuity of care; it consists of several steps of which selecting patients in need of it is the first one. The Blaylock Risk Assessment Screening Score (BRASS) index is a risk screening instrument which can be used early after admission to identify those patients in need of discharge planning. AIM: To test the predictive validity of the BRASS index in screening patients with post-discharge problems. DESIGN: Prospective longitudinal design with prediction instrument measured at admission, and outcomes measured at discharge and 7 and 30 days after discharge. OUTCOME MEASURES: length of stay, discharge destination, status after discharge. INSTRUMENTS: BRASS index, Problems after discharge Questionnaire, Nottingham Health Profile, COOP/WONCA charts. RESEARCH METHOD: 503 elderly patients were screened at admission with the BRASS index. Length of stay and discharge destination were measured at discharge in these same patients. Outcomes after discharge were gathered only in patients who were discharged home and with length of stay of more than 3 days (n=226); outcomes were measured by postal questionnaires at day 7 and day 30 after discharge. RESULTS: patients identified by the BRASS index as high risk are frequently not discharged home and have a longer length of stay. The BRASS scores correlate significantly with the outcome scores after discharge: the higher the BRASS score, the higher the difficulty score after discharge on all domains. However, the sensitivity of the BRASS index is rather low. CONCLUSION: This study demonstrates that the BRASS index is a good predictor instrument for indicating patients who are not discharged home, that the BRASS scores correlate significantly with problems experienced after discharge and that it has high specificity to predict patients with problems after discharge. Clinical use, however, is limited due to the low sensitivity. The BRASS index is a promising case-finding instrument for discharge planning, but needs further development.

Aged↗
PubMed2003

Membrane-specific targeting of green fluorescent protein by the Tat pathway in the cyanobacterium Synechocystis PCC6803.

The transport and sorting of extracytoplasmic proteins in cyanobacteria is made complex by the presence of a highly differentiated membrane system. Proteins destined for the periplasm and thylakoid lumen are initially transported by Sec- and Tat-type pathways but little is known of the mechanisms that ultimately direct them to the correct destinations. We have generated a Synechocystis PCC6803 transformant that expresses a fusion protein comprising the Tat-specific targeting signal of Escherichia coli TorA linked to green fluorescent protein (GFP). Immunoblotting indicates the presence of mature-size GFP but no precursor form, demonstrating that efficient translocation has taken place. Confocal microscopy and immunogold electron microscopy reveal GFP to be almost exclusively located in the periplasm, with almost no protein evident in the thylakoid network. These data point to the operation of highly effective sorting pathways for soluble proteins in this cyanobacterium. The observed sorting of the GFP suggests that either (a) the Tat apparatus is located only in the plasma membrane or (b) the TorA-GFP is targeted across either membrane but the GFP is subsequently directed to the periplasm, perhaps by a default sorting pathway to this compartment.

Bacterial Proteins↗