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Increased Survival (increased + survival)
Selected AbstractsTriage and mortality in 2875 consecutive trauma patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010R. MEISLER Background: Most studies on trauma and trauma systems have been conducted in the United States. We aimed to describe the factors predicting mortality in European trauma patients, with focus on triage. Methods: We prospectively registered all trauma patients in Eastern Denmark over 12 consecutive months. We analysed the flow of trauma patients through the system, the time spent at different locations, and we assessed the risk factors of mortality. Results: We included 2875 trauma patients, of whom 158 (5.5%) died before arrival at the hospital. Most patients (75.3%) were brought to local hospitals and patients primarily (n=82) or secondarily triaged (n=203) to the level I trauma centre were the most severely injured. Secondarily transferred patients spent a median of 150 min in the local hospital before transfer to the level I trauma centre and 48 min on transportation. Severe injury with an injury severity score >15 was seen in 345 patients, of whom 118 stayed at the local hospital. They had a significantly higher mortality than 116 of those secondarily transferred [45/118, 38.1% vs. 11/116, 9.7% (P<0.0001)]. Mortality within 30 days was 4.3% in admitted patients, and significant risk factors of death were violence [odds ratio (OR)=5.72], unconsciousness (OR=4.87), hypotension (OR=4.96), injury severity score >15 (OR=27.42), and age. Conclusions: Around 50% of all trauma deaths occurred at the scene. Increased survival of severely injured patients may be achieved by early transfer to highly specialised care. [source] Increased survival and breeding performance of double breeders in little penguins Eudyptula minor, New Zealand: evidence for individual bird quality?JOURNAL OF AVIAN BIOLOGY, Issue 2 2003Edda Johannesen The little penguin Eudyptula minor is unique among penguin species in being able to fledge chicks from two clutches in one breeding season. Pairs laying two clutches in a given season make a higher reproductive investment, and may be rewarded by a higher reproductive success as they may raise twice as many chicks as pairs laying one clutch. The higher effort made by pairs laying two clutches could correlate negatively with survival, future reproductive performance or offspring survival, indicating a cost of reproduction. Conversely, a positive relationship between the number of clutches produced in a given breeding season and survival, future reproductive performance or offspring survival would indicate that birds laying two clutches belonged to a category of birds with higher fitness, compared to birds laying only one clutch in the season. In this study we used a long-term data set taken from an increasing population of little penguins in Otago, SE New Zealand. We modelled the relationship between the number of clutches laid in a breeding season and survival probability, reproductive performance in the next breeding season and first year survival of offspring using capture-recapture modelling. Birds laying two clutches produced 1.7 times more fledglings during a breeding season than pairs laying one clutch. We found that birds laying two clutches had a higher probability of breeding in the following breeding season, a higher probability of laying two clutches in the following breeding season and a higher survival probability. There was no overall difference in post-fledging survival between the young of birds producing one clutch and the young of birds producing two clutches. However, the survival of young of single clutch breeders declined with laying date, whereas the young of double clutch breeders had the same survival rate irrespective of laying date. For a subset of data with birds of known age, we found evidence that the probability of laying two clutches increased with age. However, there were also indications for differences among birds in the tendency to lay two clutches that could not be attributed to age. We tentatively interpret our results as evidence of quality difference among little penguin breeders. [source] Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Peter Klivenyi Abstract There is substantial evidence that excitotoxicity and oxidative damage may contribute to Huntington's disease (HD) pathogenesis. We examined whether the novel anti-oxidant compound BN82451 exerts neuroprotective effects in the R6/2 transgenic mouse model of HD. Oral administration of BN82451 significantly improved motor performance and improved survival by 15%. Oral administration of BN82451 significantly reduced gross brain atrophy, neuronal atrophy and the number of neuronal intranuclear inclusions at 90 days of age. These findings provide evidence that novel anti-oxidants such as BN82451 may be useful for treating HD. [source] Suitability of Golf Course Ponds for Amphibian Metamorphosis When Bullfrogs Are RemovedCONSERVATION BIOLOGY, Issue 1 2008MICHELLE D. BOONE charcas en campos de golf; competencia; depredación; metamorfosis de anfibios; Rana catesbeiana Abstract:,Managing areas designed for human recreation so that they are compatible with natural amphibian populations can reduce the negative impacts of habitat destruction. We examined the potential for amphibians to complete larval development in golf course ponds in the presence or absence of overwintered bullfrog tadpoles (Rana catesbeiana), which are frequently found in permanent, human-made ponds. We reared larval American toads (Bufo americanus), southern leopard frogs (R. sphenocephala), and spotted salamanders (Ambystoma maculatum) with 0 or 5 overwintered bullfrog tadpoles in field enclosures located in ponds on golf courses or in experimental wetlands at a reference site. Survival to metamorphosis of American toads, southern leopard frogs, and spotted salamanders was greater in ponds on golf courses than at reference sites. We attributed this increased survival to low abundance of insect predators in golf course ponds. The presence of overwintered bullfrogs, however, reduced the survival of American toads, southern leopard frogs, and spotted salamanders reared in golf course ponds, indicating that the suitability of the aquatic habitats for these species partly depended on the biotic community present. Our results suggest that ponds in human recreational areas should be managed by maintaining intermediate hydroperiods, which will reduce the presence of bullfrog tadpoles and predators, such as fish, and which may allow native amphibian assemblages to flourish. Resumen:,El manejo de áreas diseñadas para la recreación humana de manera que sean compatibles con las poblaciones naturales de anfibios puede reducir los impactos negativos de la destrucción del hábitat. Examinamos el potencial de anfibios para completar el desarrollo larvario en lagos en campos de golf en presencia o ausencia de renacuajos de Rana catesbeiana, que frecuentemente son encontrados en charcas artificiales permanentes. Criamos sapos (Bufo americanus), ranas (R. sphenocephala) y salamandras manchadas (Ambystoma maculatum) con cero o cinco renacuajos de R. catesbeiana en encierros localizados en charcas en campos de golf o en humedales experimentales en un sitio de referencia. La supervivencia hasta la metamorfosis de B. americanus, R. sphenocephala y A. maculatum fue mayor en los campos de golf que en los sitios de referencia. Atribuimos este incremento en la supervivencia a la baja abundancia de insectos depredadores en las charcas de los campos de golf. Sin embargo, la presencia de renacuajos de R. catesbeiana redujo la supervivencia de B. americanus, R. sphenocephala y A. maculatum en los campos de golf, indicando que el beneficio de los hábitats acuáticos para estas especies dependía parcialmente de la comunidad biótica presente. Nuestros resultados sugieren que las charcas en áreas recreativas deberían ser manejadas manteniendo hidroperíodos intermedios, que reducirían la presencia de renacuajos de R. catesbeiana y de depredadores, como peces, y que permitirían que florezcan ensambles de anfibios nativos. [source] A phenotypically distinct subset of immature B cells exhibits partial activation, increased survival, and preferential expression of VhS107EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003Emily Abstract We have observed that immature B cells (IgMlowIgD,) in the bone marrow of adult BALB/c mice exhibit heterogeneity, with a distinct subpopulation (,4,10%) expressing the CD43/S7 surface protein. These CD43/S7+ immature B cells often express other surface antigens associated with B cell activation (CD5, CD11b, PD-1). Generation of optimal numbers of CD43/S7+ immature B cells requires expression of a functional Btk protein, consistent with activation as a requisite for the CD43/S7+ immature B cell phenotype. Like typical CD43/S7, immature B cells, the CD43/S7+ immature B cells are predominantly resting cells, which are derived from cycling bone marrow B cell precursors. The CD43/S7+ immature B cell population exhibits enhanced survival in vivo upon administration of the apoptosis-inducing corticosteroid, dexamethasone. Finally, CD43/S7+ immature B cells show a fourfold increase in incidence of VhS107 , heavy chain expression compared to the CD43/S7, immature B cells. Therefore, in adult murine bone marrow, the presence of a phenotypically distinct immature B cellpopulation can be demonstrated which has undergone partial activation leading to increased survival and BCR-dependent Vh repertoire selection. [source] ,Activation-induced cell death': a special program able to preserve the homeostasis of the skin?EXPERIMENTAL DERMATOLOGY, Issue 1 2002Giuseppe De Panfilis Abstract: The ,activation-induced cell death' (AICD) is a molecular system leading to death of antigen-activated T lymphocytes, in order to avoid accumulation of harmful cytokine-releasing cells. This article reviews both the molecular mechanisms working in AICD and the role played by such mechanisms in preventing a number of skin diseases. Specifically, because AICD removes activated and autoreactive T cells through a CD95-/CD95-L-mediated suicide, skin diseases were scrutinized in which such valuable machinery could be lacking. Indeed, at least some inflammatory skin diseases, including psoriasis and atopic dermatitis, can be sustained by an increased survival of activated T lymphocytes associated with deficient CD95-/CD95-L-mediated AICD of such strong pro-inflammatory cells. In addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen planus and other lichenoid tissue reactions, can be related to autoreactive T lymphocytes which could be unable to undergo CD95-/CD95-L-mediated AICD. Finally, a lack of AICD may be executive even in favoring cutaneous T cell lymphoma. Thus, because inflammatory, autoreactive and neoplastic skin diseases can be associated with a deficient CD95-/CD95-L-mediated suicide of activated T cells, AICD is likely to represent a fundamental program to preserve the homeostasis of the skin. Therapeutic approaches able to restore the AICD machinery promise to successfully treat such relevant skin diseases. [source] An update on the neuropathology of HIV in the HAART eraHISTOPATHOLOGY, Issue 6 2004J E Bell This review compares the neuropathology of highly active antiretroviral therapy (HAART)-treated HIV+ individuals with the reported central nervous system (CNS) findings from the pre-HAART era. HAART has had considerable success in combating HIV-related immune collapse and has prevented many of the former end-stage complications of AIDS. However, with increased survival times the prevalence of minor HIV-associated cognitive impairment appears to be rising among treated patients and this may be a particular risk for older individuals. HIV encephalitis (HIVE) is still prevalent in treated patients although attenuated forms of HIVE and CNS opportunistic disorders are also observed. Some subjects show very significant CNS lymphocytic infiltrates in the context of HAART-induced immune reconstitution. HIV-associated cognitive impairment correlates best with the increased presence of activated, though not necessarily infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss occur in HIV/AIDS as a basis for dementia since neurones are not themselves productively infected. Research to elucidate the mechanisms of neuronal injury in HIV/AIDS may contribute to the understanding of CNS function not only in HAART-treated subjects but also in other neurodegenerative disorders. [source] Multiple myeloma biology: lessons from the 5TMM modelsIMMUNOLOGICAL REVIEWS, Issue 1 2003Karin Vanderkerken Summary:, Multiple myeloma (MM) is a B cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable models to study these interactions. These murine models originate from spontaneously developed myeloma in elderly mice, which are propagated by in vivo transfer of the myeloma cells into young syngeneic mice. In this review we report on studies performed in the 5TMM models with special emphasis on the homing of the myeloma cells, the characterization of the migrating and proliferating clone and the identification of the isotype switch variants. The bone marrow microenvironment was further targeted with osteoprotegerin (OPG) to block the RANK/RANKL/OPG system and with potent bisphosphonates. Both treatments resulted in a significant protection against myeloma-associated bone disease, and they decreased myeloma disease, as evidenced by a lower tumor load and an increased survival of the mice. These different studies demonstrate the strength of these models, not only in unraveling basic biological processes but also in the testing of potentially new therapeutic targets. [source] Long-Term Results of Heart Transplantation for End-Stage Valvular Heart DiseaseJOURNAL OF CARDIAC SURGERY, Issue 5 2009D.Sc., F.I.C.S., M.P.H., M.Sc., Ph.D., Yanto Sandy Tjang M.D. However, the outcomes of heart transplantation for patients with end-stage valvular heart disease are less well reported. This is a substantial group of patients, many of whom have had previous cardiac surgery. They therefore may be considered a subgroup with a poor prognosis. This study reports on the outcomes of heart transplantation for patients with end-stage valvular heart disease. Patients and methods: From March 1989 to December 2004, 75 consecutive adult heart transplantations were performed for end-stage valvular heart disease. Clinical characteristics were retrieved from a computerized database. Results: The early mortality risk in heart transplantation for end-stage valvular heart disease was 13%, compared to 8% for other indications (p = 0.12). The main causes of early death were rejection (20%) and right ventricular failure (20%). The total follow-up time was 415 patient-years. During the follow-up, another 23 patients died (55/1000 patient-years of late mortality rate), mostly due to infection (43%) and multiorgan failure (22%). Multivariable analysis demonstrated that increased waiting time to heart transplantation correlated with increased survival (HR = 0.998, p = 0.04). The survival at 1, 5, 10, and 15 years was 70%, 64%, 56%, and 46% compared to 78%, 68%, 53%, and 41% for other indications, respectively (p = 0.5). Conclusion: The outcomes of heart transplantation for patients with end-stage valvular heart disease are similar to those for other patients. Apparently, the longer the waiting time to heart transplantation the better the outcome becomes. [source] DILP-producing median neurosecretory cells in the Drosophila brain mediate the response of lifespan to nutritionAGING CELL, Issue 3 2010Susan J. Broughton Summary Dietary restriction extends lifespan in diverse organisms, but the gene regulatory mechanisms and tissues mediating the increased survival are still unclear. Studies in worms and flies have revealed a number of candidate mechanisms, including the target of rapamycin and insulin/IGF-like signalling (IIS) pathways and suggested a specific role for the nervous system in mediating the response. A pair of sensory neurons in Caenorhabditis elegans has been found to specifically mediate DR lifespan extension, but a neuronal focus in the Drosophila nervous system has not yet been identified. We have previously shown that reducing IIS via the partial ablation of median neurosecretory cells in the Drosophila adult brain, which produce three of the seven fly insulin-like peptides, extends lifespan. Here, we show that these cells are required to mediate the response of lifespan to full feeding in a yeast dilution DR regime and that they appear to do so by mechanisms that involve both altered IIS and other endocrine effects. We also present evidence of an interaction between these mNSCs, nutrition and sleep, further emphasising the functional homology between the DILP-producing neurosecretory cells in the Drosophila brain and the hypothalamus of mammals in their roles as integration sites of many inputs for the control of lifespan and behaviour. [source] Correlated responses to selection for stress resistance and longevity in a laboratory population of Drosophila melanogasterJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 4 2005O. A. BUBLIY Abstract Laboratory studies on Drosophila have revealed that resistance to one environmental stress often correlates with resistance to other stresses. There is also evidence on genetic correlations between stress resistance, longevity and other fitness-related traits. The present work investigates these associations using artificial selection in Drosophila melanogaster. Adult flies were selected for increased survival after severe cold, heat, desiccation and starvation stresses as well as increased heat-knockdown time and lifespan (CS, HS, DS, SS, KS and LS line sets, respectively). The number of selection generations was 11 for LS, 27 for SS and 21 for other lines, with selection intensity being around 0.80. For each set of lines, the five stress-resistance parameters mentioned above as well as longevity (in a nonstressful environment) were estimated. In addition, preadult developmental time, early age productivity and thorax length were examined in all lines reared under nonstressful conditions. Comparing the selection lines with unselected control revealed clear-cut direct selection responses for the stress-resistance traits. Starvation resistance increased as correlated response in all sets of selection lines, with the exception of HS. Positive correlated responses were also found for survival after cold shock (HS and DS) and heat shock (KS and DS). With regard to values of resistance across different stress assays, the HS and KS lines were most similar. The resistance values of the SS lines were close to those of the LS lines and tended to be the lowest among all selection lines. Developmental time was extended in the SS and KS lines, whereas the LS lines showed a reduction in thorax length. The results indicate a possibility of different multiple-stress-resistance mechanisms for the examined traits and fitness costs associated with stress resistance and longevity. [source] Does the capacity for energy utilization affect the survival of post-smolt Atlantic salmon, Salmo salar L., during natural outbreaks of infectious pancreatic necrosis?JOURNAL OF FISH DISEASES, Issue 7 2007K-A Rørvik Abstract If osmotic stress and reduced seawater tolerance are predisposing factors for infectious pancreatic necrosis (IPN) outbreaks in farmed Atlantic salmon, increased survival by enhancing access to energy would be expected. The aim of the present study was, therefore, to increase energy access in 1-year old Atlantic salmon after sea transfer by increasing the level of dietary fat, by exchanging some of the dietary oil with more easily oxidized medium chain triacylglycerols, or by dietary supplementation of potentially energy enhancing additives such as clofibrate and tetradecylthioacetic acid (TTA). A natural outbreak of IPN occurred 8 weeks after sea transfer, and a significant dietary effect explaining 76% of the variation in mortality was observed. Relative percentage survival for the fish fed TTA in sea water was 70% when compared with the unsupplemented control, reducing mortality from 7.8 to 2.3%. Muscle fat content and plasma chloride were related to IPN mortality, suggesting that reduced hypoosmoregulatory capacity might be a predisposing factor to the onset of an IPN outbreak. Based on the observation of a threefold increase in white muscle mitochondrial fatty acid oxidizing activity by TTA, it is suggested that TTA has resulted in a re-allocation of dietary fatty acids from storage to energy producing oxidation. [source] NAALADase (GCP II) inhibitors protect in models of amyotrophic lateral sclerosis (ALS)JOURNAL OF NEUROCHEMISTRY, Issue 2002A. G. Thomas Chronic glutamate toxicity is implicated in the pathogenesis of ALS. The neuropeptide N-acetyl-aspartyl glutamate (NAAG) appears to function both as a storage form for glutamate and as a neuromodulator at glutamatergic synapses. Catabolism of NAAG by N-acetylated-,-linked acidic dipeptidase (NAALADase; also termed glutamate carboxypeptidase II), yields N-acetyl aspartate (NAA) and glutamate. Since prior studies demonstrate an up-regulation of NAALADase in motor cortex and increased levels of NAA and glutamate in the CSF of ALS patients, we hypothesized that inhibition of NAALADase could protect against neuronal degeneration in ALS. Neuroprotective effects of two NAALADase inhibitors were assessed. 2-(Phosphonomethyl)pentanedioic acid (2-PMPA) decreased motor neuron loss and prevented loss of choline acetyltransferase (ChAT) activity in an in vitro model of ALS wherein chronic glutamate toxicity was induced by blocking glutamate transport. Gross morphology was preserved in 2-PMPA-treated cultures. In a SOD-1 transgenic mouse model of ALS, oral administration of a structurally different NAALADase inhibitor (GPI 5693) increased survival by 29 days and delayed onset of clinical symptoms by 17 days. Preliminary analysis of spinal cord pathology revealed severe neuronal depletion and astrocytosis with white matter changes in control mice. In mice treated with GPI 5693, normal neuronal populations with modest vacuolar changes were observed. These data suggest that NAALADase inhibition may provide an exciting therapeutic approach to the devastating disease, ALS. [source] RNA interference-mediated knockdown of ,-synuclein protects human dopaminergic neuroblastoma cells from MPP+ toxicity and reduces dopamine transportJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2007Timothy M. Fountaine Abstract The critical observation in the pathology of Parkinson's disease (PD) is that neurodegeneration is largely restricted to dopaminergic neurons that develop cytoplasmic inclusions called Lewy bodies. These aggregations contain the protein ,-synuclein. Furthermore, it is becoming apparent that ,-synuclein expression levels are a major factor in PD pathogenesis. Patients with additional copies of the ,-synuclein gene develop PD with a severity proportional to levels of ,-synuclein overexpression. Similarly, overexpression of ,-synuclein in in vitro and in vivo models has been shown to be toxic. However, little is known about the effects of reducing ,-synuclein expression in human neurons. To investigate this, we have developed a system in which levels of ,-synuclein can be acutely suppressed by using RNA interference (RNAi) in a physiologically relevant human dopaminergic cellular model. By using small interfering RNA (siRNA) molecules targeted to endogenous ,-synuclein, we achieved 80% protein knockdown. We show that ,-synuclein knockdown has no effect on cellular survival either under normal growth conditions over 5 days or in the presence of the mitochondrial inhibitor rotenone. Knockdown does, however, confer resistance to the dopamine transporter (DAT)-dependent neurotoxin N-methyl-4-phenylpyridinium (MPP+). We then demonstrate for the first time that ,-synuclein suppression decreases dopamine transport in human cells, reducing the maximal uptake velocity (Vmax) of dopamine and the surface density of its transporter by up to 50%. These results show that RNAi-mediated ,-synuclein knockdown alters cellular dopamine homeostasis in human cells and may suggest a mechanism for the increased survival in the presence of MPP+, a toxin used extensively to model Parkinson's disease. © 2006 Wiley-Liss, Inc. [source] Suggested Strategies for Ventilatory Management of Veterinary Patients with Acute Respiratory Distress SyndromeJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2001Erika R. Mueller DVM Abstract Objective: To review the current recommendations and guidelines for mechanical ventilation in humans and in animals with acute respiratory distress syndrome. Human data synthesis: Acute respiratory distress syndrome (ARDS) in humans in defined as an acute onset of bilateral, diffuse infiltrates on thoracic radiographs that are not the result of heart disease and a significant oxygenation impairment. These patients require mechanical ventilation. Research has shown that further pulmonary damage can occur as a result of mechanical ventilation. Various alveolar recruitment maneuvers and a low tidal volume with increased positive end expiratory pressure (PEEP) have been associated with an increased survival. Veterinary dat synthesis: Two veterinary reports have characterized ARDS in dogs using human criteria. There are no prospective veterinary studies using recruitment that ventilator-induced lung injury (VILI) occurs in dogs, sheep, and rats. Conclusion: Recruitment maneuvers in conjunction with low tidal volumes and PEEP keep the alveoli open for gas exchange and decrease VILI. Prospective veterinary research in needed to determine if these maneuvers and recommendation can be applied to veterinary patients. [source] Current diagnosis and management of primary sclerosing cholangitisLIVER TRANSPLANTATION, Issue 6 2008Jens J. W. Tischendorf Primary sclerosing cholangitis (PSC) is an important liver disease with major morbidity and mortality. The diagnosis of PSC is confirmed by magnetic resonance cholangiopancreaticography, and endoscopic retrograde cholangiopancreaticography is performed in patients needing therapeutic endoscopy. As a result of the unknown cause of the disease, current medical therapies are unsatisfactory. Nevertheless, high-dose ursodeoxycholic acid should be recommended for treatment of PSC patients because there is a trend toward increased survival. Dominant bile duct stenoses should be treated endoscopically. However, liver transplantation continues to be the only therapeutic option for patients with advanced disease. Estimation of prognosis and timing of liver transplantation should be determined individually for each PSC patient on the basis of all results. The diagnosis and treatment of cholangiocarcinoma (CC) still remain a challenge in PSC patients. Early diagnosis of CC certainly is a prerequisite for successful treatment with surgical resection or innovative strategies such as neoadjuvant radiochemotherapy with subsequent orthotopic liver transplantation. Therefore, endoscopic techniques such as cholangioscopy and/or intraductal ultrasound may be useful diagnostic tools in patients with stenoses suspicious for malignancy. Liver Transpl 14:735,746, 2008. © 2008. [source] Correlation of tracheal smooth muscle function with structure and protein expression during early development,PEDIATRIC PULMONOLOGY, Issue 5 2007Aaron B. Cullen MD Abstract With increased survival of premature infants, understanding the impact of development on airway function and structure is imperative. Airway smooth muscle plays a primary role in the modulation of airway function. The purpose of this study is to correlate the functional maturation of airway smooth muscle during the perinatal period with structural alterations at the cellular, ultrastructural, and molecular levels. Length-tension and dose-response analyses were performed on tracheal rings acquired from preterm and term newborn lambs. Subsequent structural analyses included isolated airway smooth muscle cell length, electron microscopy, and myosin heavy chain isoform expression measurements. Functionally the compliance, contractility, and agonist sensitivity of the tracheal rings matured during preterm to term development. Structurally, isolated cell lengths and electron microscopic ultrastructure were not significantly altered during perinatal development. However, expression of myosin heavy chain isoforms increased significantly across the age range analyzed, correlating with the maturational increase in smooth muscle contractility. In conclusion, the developmental alterations in tracheal function appear due, in part, to enhanced smooth muscle myosin heavy chain expression. Pediatr Pulmonol. 2007; 42:421,432. © 2007 Wiley-Liss, Inc. [source] Annotation: Paediatric HIV InfectionTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 4 2001Rebekah Lwin HIV and AIDS have made a huge global impact, permeating the social, cultural, and economic fabric of almost all nations. The first cases of HIV infection in children were reported in the late 1980s and numbers have since risen steadily throughout the world, with some of the poorest and least developed countries experiencing the highest prevalence. Combined drug regimes have changed the course of HIV-related illness and brought increased survival to those for whom treatment is available. With this, however, have come fresh concerns relating to drug resistance, treatment adherence, and the risk of second-generation vertical transmission as HIV-infected children now survive into adulthood and beyond. The psychological literature has addressed issues such as the direct effect of HIV on child development, social and cultural attitudes, family functioning and support, affected children and orphans of HIV-infected parents, sexual health education, disclosure of diagnosis, and long-term clinical management. The outcome for those living in wealthier countries is optimistic, but the spread of this virus in the rest of the world and its impact on family life and social and political systems remains of great concern. [source] Neurotrophic effects of GM1 ganglioside and electrical stimulation on cochlear spiral ganglion neurons in cats deafened as neonatesTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2007Patricia A. Leake Abstract Previous studies have shown that electrical stimulation of the cochlea by a cochlear implant promotes increased survival of spiral ganglion (SG) neurons in animals deafened early in life (Leake et al. [1999] J Comp Neurol 412:543,562). However, electrical stimulation only partially prevents SG degeneration after deafening and other neurotrophic agents that may be used along with an implant are of great interest. GM1 ganglioside is a glycosphingolipid that has been reported to be beneficial in treating stroke, spinal cord injuries, and Alzheimer's disease. GM1 activates trkB signaling and potentiates neurotrophins, and exogenous administration of GM1 has been shown to reduce SG degeneration after hearing loss. In the present study, animals were deafened as neonates and received daily injections of GM1, beginning either at birth or after animals were deafened and continuing until the time of cochlear implantation. GM1-treated and deafened control groups were examined at 7,8 weeks of age; additional GM1 and no-GM1 deafened control groups received a cochlear implant at 7,8 weeks of age and at least 6 months of unilateral electrical stimulation. Electrical stimulation elicited a significant trophic effect in both the GM1 group and the no-GM1 group as compared to the contralateral, nonstimulated ears. The results also demonstrated a modest initial improvement in SG density with GM1 treatment, which was maintained by and additive with the trophic effect of subsequent electrical stimulation. However, in the deafened ears contralateral to the implant SG soma size was severely reduced several months after withdrawal of GM1 in the absence of electrical activation. J. Comp. Neurol. 501:837,853, 2007. © 2007 Wiley-Liss, Inc. [source] Interactions between Fusarium species from sugarcane and the stalk borer, Eldana saccharina (Lepidoptera: Pyralidae)ANNALS OF APPLIED BIOLOGY, Issue 3 2009S.A. McFarlane Abstract In this study, beneficial relationships between Fusarium species in sugarcane and the stalk borer, Eldana saccharina (Lepidoptera: Pyralidae) were demonstrated in vitro. In addition, Fusarium species with antagonistic properties were found to inhabit sugarcane. Attenuated Fusarium isolates from sugarcane stalks collected across the South African sugar industry were incorporated into diet formulated to mass rear E. saccharina. Of the over 200 Fusarium isolates obtained, 10 that significantly improved the survival and development of E. saccharina larvae and considered to be beneficial were selected for further study, as were 10 that were detrimental or antagonistic to the stalk borer. Twelve of the selected isolates were identified as F. sacchari by direct sequencing of translation elongation factor-1, fragments, eight of which resulted in reduced numbers of surviving larvae and significantly lower larval masses. F. proliferatum isolates resulted in increased survival and mass of E. saccharina and three of the five isolates assigned to the F. pseudonygamai group enhanced E. saccharina development. Results from olfactory choice experiments suggested the production of attractive and repellent metabolites by certain isolates. Findings from this study may offer additional or alternative strategies for managing E. saccharina infestation of sugarcane. [source] Slowed progression in models of huntington disease by adipose stem cell transplantation,ANNALS OF NEUROLOGY, Issue 5 2009Soon-Tae Lee MD Objective Adipose-derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models. Methods ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)-induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60-day-old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we treated mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media. Results In the QA model, human ASCs reduced apomorphine-induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota-Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC-transplanted R6/2 mice expressed elevated levels of peroxisome proliferator-activated receptor , coactivator-1, (PGC-1,) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1, expression. Interpretation Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671,681 [source] Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates,ANNALS OF NEUROLOGY, Issue 3 2009Stefano Pluchino MD Objective Transplanted neural stem/precursor cells (NPCs) display peculiar therapeutic plasticity in vivo. Although the replacement of cells was first expected as the prime therapeutic mechanism of stem cells in regenerative medicine, it is now clear that transplanted NPCs simultaneously instruct several therapeutic mechanisms, among which replacement of cells might not necessarily prevail. A comprehensive understanding of the mechanism(s) by which NPCs exert their therapeutic plasticity is lacking. This study was designed as a preclinical approach to test the feasibility of human NPC transplantation in an outbreed nonhuman primate experimental autoimmune encephalomyelitis (EAE) model approximating the clinical and complex neuropathological situation of human multiple sclerosis (MS) more closely than EAE in the standard laboratory rodent. Methods We examined the safety and efficacy of the intravenous (IV) and intrathecal (IT) administration of human NPCs in common marmosets affected by human myelin oligodendrocyte glycoprotein 1-125,induced EAE. Treatment commenced upon the occurrence of detectable brain lesions on a 4.7T spectrometer. Results EAE marmosets injected IV or IT with NPCs accumulated lower disability and displayed increased survival, as compared with sham-treated controls. Transplanted NPCs persisted within the host central nervous system (CNS), but were also found in draining lymph nodes, for up to 3 months after transplantation and exhibited remarkable immune regulatory capacity in vitro. Interpretation Herein, we provide the first evidence that human CNS stem cells ameliorate EAE in nonhuman primates without overt side effects. Immune regulation (rather than neural differentiation) is suggested as the major putative mechanism by which NPCs ameliorate EAE in vivo. Our findings represent a critical step toward the clinical use of human NPCs in MS. Ann Neurol 2009;66:343,354 [source] Effects of protein hydrolysate in weaning diets for Atlantic cod (Gadus morhua L.) and Atlantic halibut (Hippoglossus hippoglossus L.)AQUACULTURE NUTRITION, Issue 2 2009A. KVÅLE Abstract The study aims to test whether predigested dietary protein enhances the utilization of formulated diets at weaning, and also whether it stimulates intestinal maturation. In this study, Atlantic cod [Gadus morhua L.; 41 days posthatch (dph)] and Atlantic halibut [Hippoglossus hippoglossus L.; 63 days postfirst feeding (dpff)] were weaned onto diets with graded levels of protein hydrolysate. By increasing the inclusion of dietary protein as hydrolysate from 0 to 400 g kg,1, cod increased the rate of survival from 7 ± 1% to 18 ± 2% (82 dph; regression, P = 4*10,7). In halibut, the survival rate decreased from 57 ± 9% to 22 ± 7% as the inclusion of protein in the form of hydrolysate increased from 0 to 450 g kg,1 (119 dpff; regression, P = 8*10,5). Growth was not affected in any of the species. Results in specific activities of the intestinal enzymes leucine aminopeptidase (LAP) and alkaline phospatase (AP) supported the results in survival in halibut and partly also in cod, by showing increased activities in groups with increased survival (anova, P < 0.05). The lower optimal level of hydrolysed protein in halibut than in cod is suggested mainly because of a slower feeding practice in halibut, which allows more extensive nutrient leaching before ingestion. [source] Role of CD21 antigen in diffuse large B-cell lymphoma and its clinical significanceBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004Masaki Otsuka Summary Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B-cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3·7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2·36, P < 0·05). As a result of these clinical observations, we generated CD21-overexpressed (CD21+) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector-only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21+ transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P < 0·05). Interestingly, all established CD21+ transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti-CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules. [source] Elevated levels of transferrin receptor 2 mRNA, not transferrin receptor 1 mRNA, are associated with increased survival in acute myeloid leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2004Tsuyoshi Nakamaki Summary Transferrin receptor 1 (TfR1) is a type II membrane protein that mediates cellular iron uptake. Transferrin receptor 2(TfR2), another receptor for transferrin (Tf), has recently been cloned. We examined expression levels of TfR1, TfR2-, (membrane form) and TfR2-, (non-membrane form) transcripts in cells from 67 patients with de novo acute myeloid leukaemia (AML) using reverse transcription-polymerase chain reaction (RT-PCR), and correlated the results with a variety of clinical features and disease outcomes of these patients. Significant correlations were noted between the levels of both TfR1 and TfR2-, (r = 0·771, P < 0·001) and TfR1 and TfR2-, (r = 0·534, P < 0·001). Unexpectedly, initial white blood cell (WBC) counts were inversely correlated with levels of expression of either TfR1(r = ,0·357, P = 0·003), TfR2-, (r = ,0·486, P < 0·0001), or TfR2-, (r = ,0·435, P = 0·0003). Only TfR2 expression was significantly associated with either serum iron (r = ,0·270, P = 0·045) or serum ferritin (r = ,0·364, P = 0·008). Multivariate analyses using Cox's proportional hazard model showed that elevated TfR2-,, but not TfR1 or TfR2-, mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2-, and TfR2-, survived significantly longer than a group without high expression of both of them (P < 0·01 by log-rank). The present study suggests that (i) TfRs-independent iron uptake might have an important role in in vivo proliferation of AML cells; (ii) expression of TfR2 (especially the , form) is a novel prognostic factor for patients with AML. [source] Single-centre vs. population-based outcome data of extremely preterm infants at the limits of viabilityACTA PAEDIATRICA, Issue 9 2009Patrizia Kutz Abstract Aim:, In response to the disappointing outcome data of the population-based EPICure study published in 2000, we compared the outcome of infants 22 0/7 to 25 6/7 weeks of gestational age (GA) in a single tertiary care centre 2000,2004 with that of EPICure. Methods:, EPICure tools and definitions, including 30 months' Bayley Scales. Results:, Of 83 infants <26 weeks born alive, more were admitted to intensive care , 82% vs. 68% (p < 0.0001) , and more infants survived to discharge (57% vs. 26%, p < 0.0001; 69% vs. 39%, p < 0.01, of those admitted to intensive care). More infants, as a percentage of live births, survived without severe (41%, 34/83 vs. 20%, 233/1185, p < 0.0001) or overall disability (22%, 18/83 vs. 13%, 155/1185, p = 0.03). However, at the border of viability , GA 23 and 24 weeks , the rate of infants surviving without overall disability was not significantly higher (13%, 6/45 vs. 9%, 56/623). Conclusion:, In infants <26 weeks of GA, increased rates of survival and survival without disability were observed in a single-centre inborn cohort born 5,8 years later than the EPICure cohort. This did not translate into increased survival without overall disability in infants of 23,24 weeks of GA. [source] | ||||||||||||||||