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Sample records for a-i showed severe

  1. Images Show Severity of California Drought

    NASA Image and Video Library

    2014-07-23

    The effects of California severe multiyear drought are seen in this pair of images acquired by NASA Terra spacecraft of the area northeast of Madera, in the Sierra Nevada Moutains foothills between Yosemite National Park and the San Joaquin Valley

  2. Apolipoprotein B and A-I ratio predicts severe acute pancreatitis.

    PubMed

    Huh, Ji Hye; Jung, Saehyun; Cho, Seung Kook; Lee, Kyong Joo; Kim, Jae Woo

    2017-07-05

    Severe acute pancreatitis (SAP) has considerable mortality and morbidity rates. Although many indices have been developed to classify the severity of acute pancreatitis (AP), an optimal method for predicting SAP has not been identified. The ratio of apolipoprotein B to A-I (apoB/A-I) is associated with metabolic syndrome and inflammatory status. This study investigated the association between severity of AP and serum apoB/A-I ratio. Patients with AP were prospectively enrolled at Yonsei University Wonju College of Medicine from March 2015 to August 2016. The severity of AP was assessed according to the revised Atlanta classification criteria (Atlanta 2012). Of 191 patients with AP, 134 (70.2%) had mild AP, 42 (22%) had moderately severe AP, and 15 (7.9%) had SAP; apoB/A-I ratio was highest in patients with SAP (P = 0.001). The apoB/A-I ratio was positively correlated with Atlanta classification, computed tomography severity index, and Bedside index for severity of AP. The apoB/A-I ratio showed the highest predictive value for SAP in patients with AP compared with apolipoprotein B or apolipoprotein A-I alone. Serum apoB/A-I ratio appears to have value for predicting SAP in patients with AP. This article is protected by copyright. All rights reserved.

  3. Severe weather as a spectacle: the Meteo-Show

    NASA Astrophysics Data System (ADS)

    Orbe, Iñaki; Gaztelumendi, Santiago

    2017-06-01

    In this work we focus on perhaps one of the worst journalist practice when dealing with severe weather, the Meteo-Show or the extended practice, especially in TV, for using weather and meteorology for spectacle. Journalism today has found weather information in a real goldmine in terms of audience due to the growing public interest in this matter. However, as it happens with other content, sensationalism and exaggeration have also reached weather information, primarily when episodes of adverse nature (snow, heavy rain, floods, etc.) are addressed. In this paper we look to identify the worst practices in weather communication through analysis of examples from real journalist work. We present some keys to understand this trend, highlighting the ingredients that are present in the worst Meteo-show.

  4. Giant primary angiosarcoma of the small intestine showing severe sepsis.

    PubMed

    Takahashi, Mizuna; Ohara, Masanori; Kimura, Noriko; Domen, Hiromitsu; Yamabuki, Takumi; Komuro, Kazuteru; Tsuchikawa, Takahiro; Hirano, Satoshi; Iwashiro, Nozomu

    2014-11-21

    Primary malignant tumors of the small intestine are rare, comprising less than 2% of all gastrointestinal tumors. An 85-year-old woman was admitted with fever of 40 °C and marked abdominal distension. Her medical history was unremarkable, but blood examination showed elevated inflammatory markers. Abdominal computed tomography showed a giant tumor with central necrosis, extending from the epigastrium to the pelvic cavity. Giant gastrointestinal stromal tumor of the small intestine communicating with the gastrointestinal tract or with superimposed infection was suspected. Because no improvement occurred in response to antibiotics, surgery was performed. Laparotomy revealed giant hemorrhagic tumor adherent to the small intestine and occupying the peritoneal cavity. The giant tumor was a solid tumor weighing 3490 g, measuring 24 cm × 17.5 cm × 18 cm and showing marked necrosis. Histologically, the tumor comprised spindle-shaped cells with anaplastic large nuclei. Immunohistochemical studies showed tumor cells positive for vimentin, CD31, and factor VIII-related antigen, but negative for c-kit and CD34. Angiosarcoma was diagnosed. Although no postoperative complications occurred, the patient experienced enlargement of multiple metastatic tumors in the abdominal cavity and died 42 d postoperatively. The prognosis of small intestinal angiosarcoma is very poor, even after volume-reducing palliative surgery.

  5. Sperm of patients with severe asthenozoospermia show biochemical, molecular and genomic alterations.

    PubMed

    Bonanno, Oriana; Romeo, Giulietta; Asero, Paola; Pezzino, Franca Maria; Castiglione, Roberto; Burrello, Nunziatina; Sidoti, Giuseppe; Frajese, Giovanni Vanni; Vicari, Enzo; D'Agata, Rosario

    2016-12-01

    The multifactorial pathological condition, that is, severe low sperm motility is a frequent cause of infertility. However, mechanisms underlying the development of this condition are not completely understood. Single abnormalities have been reported in sperm of patients with asthenozoospermia. In this study, we characterized, in 22 normozoospermic men and in 37 patients with asthenozoospermia, biochemical, molecular and genomic abnormalities that frequently occur in sperm of patients with asthenozoospermia. We evaluated a panel of sperm biomarkers that may affect the motility and fertilizing ability of sperm of patients with severe asthenozoospermia. Since reactive oxygen species (ROS) production is involved in the pathogenesis of such sperm abnormalities, we determined the association between ROS production and sperm abnormalities. High percentage of patients with severe asthenozoospermia showed increased basal and stimulated ROS production. Moreover, these patients showed increased mitochondrial DNA (mtDNA) copy number but decreased mtDNA integrity and they were associated with elevated ROS levels. Furthermore, mitochondrial membrane potential was also significantly decreased and again associated with high ROS production in these patients. However, the rate of nuclear DNA fragmentation was increased only in less than one-fifth of these patients. An important cohort of these patients showed multiple identical biochemical, molecular and genomic abnormalities, which are typical manifestations of oxidative stress. The most frequent association was found in patients with high ROS levels, increased mtDNA copy number and decreased integrity, and low MMP. A smaller cohort of the aforementioned patients also showed nDNA fragmentation. Therefore, patients with asthezoospermia likely present reduced fertilizing potential because of such composed abnormalities.

  6. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

    PubMed

    Bonafede, Lucas; Ficicioglu, Can H; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Mills, Monte D; Forbes, Brian J; Davidson, Stefanie L; Binenbaum, Gil; Kaplan, Paige B; Nichols, Charles W; Verloo, Patrick; Leroy, Bart P; Maguire, Albert M; Aleman, Tomas S

    2015-12-01

    To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

  7. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    PubMed Central

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  8. Microsatellites haplotyping of CF chromosomes shows linkage disequilibrium and several founder effects in Brittany (France)

    SciTech Connect

    Raguenes, O.; Ferec, C.; Mercier, B.

    1994-09-01

    A large study on cystic fibrosis (CF) is underway in Brittany (France). It is based on 902 CF patients distributed in 795 families who were or are still followed at the {open_quotes}Centre Helio-Marin{close_quotes} in Roscoff and/or were subjected to a molecular analysis at the {open_quotes}Centre de Biogenetique{close_quotes} in Brest. At present, the CF mutations have been identified in 309 patients born in Brittany, most of them of Celtic origin. A microsatellite (MS) study using IVS 17b TA, IVS 17b CA and IVS 8 CA was also completed in 63 CF patients and their parents (carriers of the {Delta}F508 mutation or the G551D mutation or the 1078delT mutation or the W846X mutation). All the 21 chromosomes carrying the 1078delT mutation had the same MS haplotype (16-21-13), which was also found on 9 of the 83 non-CF chromosomes analyzed. All the 16 chromosomes with the G551D mutation carried another MS haplotype (16-7-17), which was also found on 13.3% of the non-CF chromosomes. All the 6 chromosomes with the W846X mutation carried the 16-32-13 haplotype, also found on 6.0% of the non-CF chromosomes. Sixteen different MS haplotypes were found among the 74 chromosomes carrying the{Delta}F508 mutation, three of them representing 74.3% (55/74) of the chromosomes. These were the 23-31-13 haplotype (31/74 - 41.9%), the 17-31-13 haplotype (11/74 - 14.9%), and the 17-32-13 haplotype (13/74 - 17.6%). These results show that the CF mutations observed in Brittany are in linkage disequilibrium with the MS haplotypes. They also suggest that their presence in Brittany is the consequence of several founder effects.

  9. Progesterone Treatment Shows Benefit in a Pediatric Model of Moderate to Severe Bilateral Brain Injury

    PubMed Central

    Geddes, Rastafa I.; Sribnick, Eric A.; Sayeed, Iqbal; Stein, Donald G.

    2014-01-01

    Purpose Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury. Methods Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28. Results The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats. Conclusion Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits. PMID:24489882

  10. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser228 severely impairs antiatherogenic capacity.

    PubMed

    Dinnes, Donna Lee M; White, Melanie Y; Kockx, Maaike; Traini, Mathew; Hsieh, Victar; Kim, Mi-Jurng; Hou, Liming; Jessup, Wendy; Rye, Kerry-Anne; Thaysen-Andersen, Morten; Cordwell, Stuart J; Kritharides, Leonard

    2016-12-01

    Apolipoprotein A-I (apoA-I) is the major component of HDL and central to the ability of HDL to stimulate ATP-binding cassette transporter A1 (ABCA1)-dependent, antiatherogenic export of cholesterol from macrophage foam cells, a key player in the pathology of atherosclerosis. Cell-mediated modifications of apoA-I, such as chlorination, nitration, oxidation, and proteolysis, can impair its antiatherogenic function, although it is unknown whether macrophages themselves contribute to such modifications. To investigate this, human monocyte-derived macrophages (HMDMs) were incubated with human apoA-I under conditions used to induce cholesterol export. Two-dimensional gel electrophoresis and Western blot analysis identified that apoA-I is cleaved (∼20-80%) by HMDMs in a time-dependent manner, generating apoA-I of lower MW and isoelectric point. Mass spectrometry analysis identified a novel C-terminal cleavage site of apoA-I between Ser(228)-Phe(229) Recombinant apoA-I truncated at Ser(228) demonstrated profound loss of capacity to solubilize lipid and to promote ABCA1-dependent cholesterol efflux. Protease inhibitors, small interfering RNA knockdown in HMDMs, mass spectrometry analysis, and cathepsin B activity assays identified secreted cathepsin B as responsible for apoA-I cleavage at Ser(228) Importantly, C-terminal cleavage of apoA-I was also detected in human carotid plaque. Cleavage at Ser(228) is a novel, functionally important post-translational modification of apoA-I mediated by HMDMs that limits the antiatherogenic properties of apoA-I.-Dinnes, D. L. M., White, M. Y., Kockx, M., Traini, M., Hsieh, V., Kim, M.-J., Hou, L., Jessup, W., Rye, K.-A., Thaysen-Andersen, M., Cordwell, S. J., Kritharides, L. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser(228) severely impairs antiatherogenic capacity. © FASEB.

  11. Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity

    PubMed Central

    Yoo, Jeong-Ah; Lee, Eun-Young; Park, Ji Yoon; Lee, Seung-Taek; Ham, Sihyun; Cho, Kyung-Hyun

    2015-01-01

    Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipid-bound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and 67 Å on native gel electrophoresis, while apoA-I showed scattered band pattern less than 71 Å. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 Å and 113 Å, while apoA-I-rHDL showed almost single band around 98 Å size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, BS3-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties. PMID:25997739

  12. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state.

    PubMed

    Jang, Wookju; Jeoung, Nam Ho; Cho, Kyung-Hyun

    2011-05-01

    Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL.

  13. Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

    PubMed Central

    Jang, Wookju; Jeoung, Nam Ho; Cho, Kyung-Hyun

    2011-01-01

    Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL. PMID:21533907

  14. Survey of severe spatial disorientation episodes in Japan Air Self-Defense Force fighter pilots showing increased severity in night flight.

    PubMed

    Takada, Yuko; Hisada, Tetsuya; Kuwada, Naruo; Sakai, Masao; Akamatsu, Tomomitsu

    2009-06-01

    Spatial disorientation (SD) is one of the most severe causative factors in aviation accidents. We analyzed the reported SD episodes to evaluate the characteristics of severe SD in fighter pilots. Three hundred seventeen cases (95.5%) of 332 total valid cases experienced SD, and the ratio of night and day SD experiences (52.7% vs. 47.3%) (p < 0.05) shows a clear prevalence of night SD events. The severity of SD episodes at night (2.23 +/- 1.09) was higher than at day (1.89 +/- 1.04) (p < 0.01). In addition, the severity of visual illusions was significantly higher at night. A significant difference was found for meteorological conditions, such as visual meteorological conditions (VMC), instrument meteorological conditions (IMC) and VMC-IMC (VI) transition, among times of days. In conclusion, the severity of the SD episodes was higher at night. This may be due to an increase in visual severe SD episodes at night.

  15. The Effects of a "Tell-Show-Try-Apply" Professional Development Package on Teachers of Students with Severe Developmental Disabilities

    ERIC Educational Resources Information Center

    Browder, Diane M.; Jimenez, Bree Ann; Mims, Pamela J.; Knight, Victoria F.; Spooner, Fred; Lee, Angel; Flowers, Claudia

    2012-01-01

    The "What Works Clearinghouse" guidelines for high-quality professional development were used to develop a Tell, Show, Try, and Apply (TSTA) method of training. This method was used to train teachers to align instruction to grade-level content for students with severe developmental disabilities. A total of 193 teachers of students who…

  16. The Effects of a "Tell-Show-Try-Apply" Professional Development Package on Teachers of Students with Severe Developmental Disabilities

    ERIC Educational Resources Information Center

    Browder, Diane M.; Jimenez, Bree Ann; Mims, Pamela J.; Knight, Victoria F.; Spooner, Fred; Lee, Angel; Flowers, Claudia

    2012-01-01

    The "What Works Clearinghouse" guidelines for high-quality professional development were used to develop a Tell, Show, Try, and Apply (TSTA) method of training. This method was used to train teachers to align instruction to grade-level content for students with severe developmental disabilities. A total of 193 teachers of students who…

  17. Ten cases of severe oral lichen planus showing granular C3 deposition in oral mucosal basement membrane zone.

    PubMed

    Hashimoto, Takashi; Fukuda, Aoi; Himejima, Akio; Morita, Shosuke; Tsuruta, Daisuke; Koga, Hiroshi; Krol, Rafal P; Ishii, Norito

    2015-01-01

    Oral lichen planus (OLP) may show depositions of immunoglobulins and complement components in oral mucosal basement membrane zone (BMZ) in direct immunofluorescence, although these finding are not frequently seen. We collected and examined ten cases of severe OLP showing granular C3 deposition in BMZ. In addition to clinical, histopathological and direct immunofluorescence assessments, we performed various immune-serological tests, including indirect immunofluorescence of normal human skin and 1M NaCl-split skin, immunoblotting of normal human epidermal and dermal extracts, recombinant proteins of BP180 NC16a and C-terminal domains, concentrated culture supernatant of HaCaT cells and purified human laminin-332, and enzyme-linked immunosorbent assays for BP230 and BP180. Direct immunofluorescence showed C3 deposition in BMZ exclusively of granular pattern in 7 cases and of both granular and linear patterns in 3 cases. The 10 cases showed no positive reactivity for either IgG or IgA antibodies in any immuno-serological tests. Detailed analyses of clinical, histopathological and immunological findings revealed striking female prevalence, although other parameters were in general characteristic of OLP. Granular C3 deposition in oral BMZ may be one of the characteristic features of severe OLP, although mechanisms for C3 deposition and its pathogenic role in OLP are currently unknown.

  18. Severe Septic Patients with Mitochondrial DNA Haplogroup JT Show Higher Survival Rates: A Prospective, Multicenter, Observational Study

    PubMed Central

    Martín, María M.; López-Gallardo, Esther; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan María; Jiménez, Alejandro; Montoya, Julio; Ruiz-Pesini, Eduardo

    2013-01-01

    Objective In a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients. Methods We conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units. We determined 30-day and 6-month survival and mtDNA haplogroup in this second cohort of 196 patients and in the global cohort (first and second cohorts combined) with 292 severe septic patients. Multiple logistic regression and Cox regression analyses were used to test for the association of mtDNA haplogroups JT with survival at 30-days and 6-months, controlling for age, sex, serum interleukin-6 levels and SOFA score. Results Logistic and Cox regression analyses showed no differences in 30-day and 6-month survival between patients with mtDNA haplogroup JT and other haplogroups in the first cohort (n=96). In the second cohort (n=196), these analyses showed a trend to higher 30-day and 6-month survival in those with haplogroup JT. In the global cohort (n=292), logistic and Cox regression analyses showed higher 30-day and 6-month survival for haplogroup JT. There were no significant differences between J and T sub-haplogroups in 30-day and 6-month survival. Conclusions The global cohort study (first and second cohorts combined), the largest to date reporting on mtDNA haplogroups in septic patients, confirmed that haplogroup JT patients showed increased 30-day and 6-month survival. This finding may be due to single nucleotide polymorphism defining the whole haplogroup JT and not separately for J or T sub-haplogroups. PMID:24069186

  19. Severe septic patients with mitochondrial DNA haplogroup JT show higher survival rates: a prospective, multicenter, observational study.

    PubMed

    Lorente, Leonardo; Iceta, Ruth; Martín, María M; López-Gallardo, Esther; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan María; Jiménez, Alejandro; Montoya, Julio; Ruiz-Pesini, Eduardo

    2013-01-01

    In a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients. We conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units. We determined 30-day and 6-month survival and mtDNA haplogroup in this second cohort of 196 patients and in the global cohort (first and second cohorts combined) with 292 severe septic patients. Multiple logistic regression and Cox regression analyses were used to test for the association of mtDNA haplogroups JT with survival at 30-days and 6-months, controlling for age, sex, serum interleukin-6 levels and SOFA score. Logistic and Cox regression analyses showed no differences in 30-day and 6-month survival between patients with mtDNA haplogroup JT and other haplogroups in the first cohort (n=96). In the second cohort (n=196), these analyses showed a trend to higher 30-day and 6-month survival in those with haplogroup JT. In the global cohort (n=292), logistic and Cox regression analyses showed higher 30-day and 6-month survival for haplogroup JT. There were no significant differences between J and T sub-haplogroups in 30-day and 6-month survival. The global cohort study (first and second cohorts combined), the largest to date reporting on mtDNA haplogroups in septic patients, confirmed that haplogroup JT patients showed increased 30-day and 6-month survival. This finding may be due to single nucleotide polymorphism defining the whole haplogroup JT and not separately for J or T sub-haplogroups.

  20. Non-Coronary Patients with Severe Chest Pain Show More Irrational Beliefs Compared to Patients with Mild Pain

    PubMed Central

    Bahremand, Mostafa; Saeidi, Mozhgan

    2015-01-01

    Background Despite providing insufficient medical evidence of the existence of a real cardiac condition, patients with non-coronary chest pain still interpret their pain incorrectly. The present study, therefore, sought to compare the irrational beliefs in non-coronary patients with mild chest pain against those with severe chest pain. Methods A cross-sectional design was used. The statistical population comprised non-coronary patients who presented to the Heart Emergency Center of Kermanshah city, Iran. Using a matching method, 96 participants were selected and studied in two groups of 48. The instruments used were the Comorbidity Index, Brief Pain Index, and the Jones Irrational Beliefs Test (short-form). The multivariate analysis of variance, chi-square test, and t-test were used for data analysis. Results Controlling for the effects of age and comorbid conditions, the severity of three types of irrational beliefs, including emotional irresponsibility (P<0.001), hopelessness changes (P<0.001), and problem avoiding (P=0.002) was higher among patients with severe chest pain (according to effect level). However, in terms of demand for approval, no difference was seen between the two groups (P=0.180). Conclusion Non-coronary patients with severe chest pain showed a greater number of irrational beliefs in comparison to patients with mild pain. Irrational beliefs are common mental occurrences in patients with non-coronary chest pain, and they should be attended to by health professionals, especially in severe non-coronary chest pain. Further investigation to determine the association between irrational beliefs and non-coronary chest pain is necessary. PMID:26217482

  1. Cervical flexion myelopathy in a patient showing apparent long tract signs: a severe form of Hirayama disease.

    PubMed

    Sakai, Kenji; Ono, Kenjiro; Okamoto, Yoshiyuki; Murakami, Hideki; Yamada, Masahito

    2011-05-01

    We describe an 18-year-old male with cervical flexion myelopathy with Hirayama disease-like features who showed apparent long tract signs. He first experienced insidious-onset hand muscle weakness and atrophy at the age of 15. Subsequently, he developed sensory disturbance in his lower limb. Neurological examination revealed atrophy and weakness in the right hand and forearm, pyramidal signs in the right lower extremity, and disturbance of superficial sensation in the lower left half of the body. Cervical magnetic resonance images and computed tomographic myelography revealed anterior displacement with compression of the cervical cord in flexion that was more apparent in the right side. The right side of the cervical cord showed severe atrophy. The mechanisms of myelopathy in our patient appeared to be same as that of "tight dural canal in flexion," which has been reported to be the mechanism of juvenile muscular atrophy of the unilateral upper extremity (Hirayama disease). Patients with Hirayama disease generally show minimal sensory signs and no pyramidal signs. An autopsy case of Hirayama disease revealed confined necrosis of the cervical anterior horn without obvious changes in the white matter. Our patient's disease progression suggests that cervical flexion myelopathy patients with severe cervical cord compression in flexion may develop extensive cervical cord injury beyond the anterior horn.

  2. Children with severe or moderate obstructive sleep apnoea syndrome show a high incidence of persistence after adenotonsillectomy.

    PubMed

    Tagaya, Mitsuhiko; Nakata, Seiichi; Yasuma, Fumihiko; Mitchell, Ron B; Sasaki, Fumihiko; Miyazaki, Soichiro; Morinaga, Mami; Otake, Hironao; Teranishi, Masaaki; Nakashima, Tsutomu

    2012-11-01

    Persistent obstructive sleep apnoea syndrome (OSAS) occurs in approximately 20% of normal-weight children after adenotonsillectomy (T&A) and, in nearly 70% of them, it is caused by adenoid regrowth. Patients with severe or moderate OSAS showed a high incidence of persistent disease even after T&A. Allergic disease, severity and large adenoid size are associated with adenoid regrowth and persistent disease. To investigate factors contributing to persistent OSAS and adenoid regrowth after T&A in normal-weight children. This was a prospective, observational study at a single institute and involved 49 normal-weight children with severe or moderate OSAS (apnoea-hypopnoea index, AHI, ≥ 5) who underwent T&A. Background information, nasal endoscopic data and pre- and postoperative polysomnographic data were collected. A third polysomnography (PSG) was performed 1.5 year postoperatively in children who subsequently developed symptoms of sleep disturbance. Thirteen children (27%, 13/49) were symptomatic 1.5 years after T&A. Allergic rhinitis (38.5% vs 11.1%, p = 0.03) and allergic disease (69.2% vs 30.6%, p = 0.02) were seen more frequently in these children. A third PSG confirmed persistent disease (AHI ≥ 5) in nine children (18.4%, 9/49). Six children (12.2%, 6/49) were diagnosed as having adenoid regrowth and three (6.1%, 3/49) underwent revision adenoidectomy.

  3. Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

    PubMed

    de Castro-Sobrinho, Juçara Maria; Rabelo-Santos, Silvia Helena; Fugueiredo-Alves, Rosane Ribeiro; Derchain, Sophie; Sarian, Luis Otávio Z; Pitta, Denise R; Campos, Elisabete A; Zeferino, Luiz Carlos

    2016-02-01

    Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia.

  4. TGFβ-dependent gene expression shows that senescence correlates with abortive differentiation along several lineages in Myc-induced lymphomas.

    PubMed

    Müller, Judith; Samans, Birgit; van Riggelen, Jan; Fagà, Giovanni; Peh K N, Raquel; Wei, Chia-Lin; Müller, Heiko; Amati, Bruno; Felsher, Dean; Eilers, Martin

    2010-12-01

    Deregulated expression of Myc under the control of an immunoglobulin enhancer induces lymphoma formation in mice. The development of lymphomas is limited by TGFβ-dependent senescence and high levels of Myc expression are continuously required to antagonize senescence. The biological processes underlying senescence are not fully resolved. We report here a comprehensive analysis of TGFβ-dependent alterations in gene expression when the Myc transgene is switched off. Our data show that Myc-induced target genes are downregulated in a TGFβ-independent manner. In contrast, TGFβ is required to upregulate a broad spectrum of genes that are characteristic of different T-cell lineages when Myc is turned off. The analysis reveals a significant overlap between these Myc-repressed genes with genes that are targets of polycomb repressive complexes in embryonic stem cells. Therefore, TGFβ-dependent senescence is associated with gene expression patterns indicative of abortive cellular differentiation along several lineages.

  5. Molecular Dynamics Simulations Show That Conformational Selection Governs the Binding Preferences of Imatinib for Several Tyrosine Kinases*

    PubMed Central

    Aleksandrov, Alexey; Simonson, Thomas

    2010-01-01

    Tyrosine kinases transmit cellular signals through a complex mechanism, involving their phosphorylation and switching between inactive and active conformations. The cancer drug imatinib binds tightly to several homologous kinases, including Abl, but weakly to others, including Src. Imatinib specifically targets the inactive, so-called “DFG-out” conformation of Abl, which differs from the preferred, “DFG-in” conformation of Src in the orientation of a conserved Asp-Phe-Gly (DFG) activation loop. However, recent x-ray structures showed that Src can also adopt the DFG-out conformation and uses it to bind imatinib. The Src/Abl-binding free energy difference can thus be decomposed into two contributions. Contribution i measures the different protein-imatinib interactions when either kinase is in its DFG-out conformation. Contribution ii depends on the ability of imatinib to select or induce this conformation, i.e. on the relative stabilities of the DFG-out and DFG-in conformations of each kinase. Neither contribution has been measured experimentally. We use molecular dynamics simulations to show that contribution i is very small, 0.2 ± 0.6 kcal/mol; imatinib interactions are very similar in the two kinases, including long range electrostatic interactions with the imatinib positive charge. Contribution ii, deduced using the experimental binding free energy difference, is much larger, 4.4 ± 0.9 kcal/mol. Thus, conformational selection, easy in Abl, difficult in Src, underpins imatinib specificity. Contribution ii has a simple interpretation; it closely approximates the stability difference between the DFG-out and DFG-in conformations of apo-Src. Additional calculations show that conformational selection also governs the relative binding of imatinib to the kinases c-Kit and Lck. These results should help clarify the current framework for engineering kinase signaling. PMID:20200154

  6. A <i>yigP mutant strain is a small colony variant of E. coli, and shows pleiotropic antibiotic resistance.

    PubMed

    Xia, Hui; Tang, Qiongwei; Song, Jie; Ye, Jiang; Wu, Haizhen; Zhang, Huizhan

    2017-09-15

    Small colony variants (SCVs) are a commonly observed subpopulation of bacteria that have a small colony size and distinctive biochemical characteristics. SCVs are more resistant to some antibiotics than the wild-type, and usually cause persistent infections in the clinic. SCV studies have been very active during the past two decades, especially of Staphylococcus aureus. However, fewer studies on Escherichia coli SCVs exist, so we studied an E. coli SCV during an experiment involving the deletion of the yigP locus. PCR and DNA sequencing revealed that the SCV was attributable to a defect in the yigP function. Furthermore, we investigated the antibiotic resistance profile of the SCV and it showed increased erythromycin, kanamycin and D-cycloserine resistance, but collateral sensitivity to ampicillin, polymyxin, chloramphenicol, tetracycline, rifampin, and nalidixic acid. We tried to determine the association between yigP and the pleiotropic antibiotic resistance of the SCV by analyzing biofilm formation, cellular morphology and coenzyme Q (Q8) production. Our results indicated that impaired Q8 biosynthesis was the primary factor that contributed to the increased resistance and collateral sensitivity of the SCV. This study offers a novel genetic basis for E. coli SCVs and an insight into the development of alternative antimicrobial strategies for clinical therapy.

  7. Physical Activity in the Life of a Woman with Severe Cerebral Palsy: Showing Competence and Being Socially Connected

    ERIC Educational Resources Information Center

    Gaskin, Cadeyrn J.; Andersen, Mark B.; Morris, Tony

    2009-01-01

    We used a life-history approach to investigate the meanings and experiences of physical activity in the life of a 25-year-old woman with severe cerebral palsy (Amy). Amy and her mother were interviewed about Amy's life and her involvement in physical activity. The conversation was audio-recorded and transcribed verbatim. We interpreted Amy's story…

  8. Nardosinanols A-I and lemnafricanol, sesquiterpenes from several soft corals, Lemnalia sp., Paralemnalia clavata, Lemnalia africana, and Rhytisma fulvum fulvum.

    PubMed

    Bishara, Ashgan; Yeffet, Dina; Sisso, Mor; Shmul, Guy; Schleyer, Michael; Benayahu, Yehuda; Rudi, Amira; Kashman, Yoel

    2008-03-01

    Ten new sesquiterpenes, nardosinanols A-I ( 1- 9) and lemnafricanol ( 10), have been isolated from several Kenyan soft corals, i.e., from Lemnalia sp., Paralemnalia clavata, Lemnalia africana, and Rhytisma fulvum fulvum. The structures and relative stereochemistry of these compounds were elucidated by interpretation of MS, COSY ( (1)H- (1)H correlations), HSQC, HMBC, and NOESY NMR spectroscopic experiments and in the case of 5 also by chemical transformation to compounds 11 and 12. Nine compounds ( 1- 9) are based on the nardosinane skeleton ( 1- 6 are nardosinanes and 7- 9 nornardosinanes). Lemnafricanol ( 10) possesses a novel tricyclic skeleton. Compounds 3, 7, and 10 were found to be toxic to brine shrimp with LC 50 values of 4.0, 0.35, and 0.32 microM, respectively.

  9. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications.

    PubMed

    Bakhuizen, Sabine E; de Haan, Timo R; Teune, Margreet J; van Wassenaer-Leemhuis, Aleid G; van der Heyden, Jantien L; van der Ham, David P; Mol, Ben Willem J

    2014-12-01

    Infants suffering from neonatal sepsis face an increased risk of early death and long-term neurodevelopmental delay. This paper analyses and summarises the existing data on short-term and long-term outcomes of neonatal sepsis, based on 12 studies published between January 2000 and 1 April 2012 and covering 3669 neonates with sepsis. Infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications such as brain damage and, or, neurodevelopmental delay. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  10. Screening for Staphylococcal Superantigen Genes Shows No Correlation with the Presence or the Severity of Chronic Rhinosinusitis and Nasal Polyposis

    PubMed Central

    Girard, Myriam; Vourexakis, Zacharias; Courtis, Antoine Des; Renzi, Gesuele; Huggler, Elzbieta; Vlaminck, Stefan; Bonfils, Pierre; Mladina, Ranko; Lund, Valerie; Schrenzel, Jacques; François, Patrice; Lacroix, Jean Silvain

    2010-01-01

    Background Staphylococcus aureus secretes numerous exotoxins which may exhibit superantigenic properties. Whereas the virulence of several of them is well documented, their exact biological effects are not fully understood. Exotoxins may influence the immune and inflammatory state of various organs, including the sinonasal mucosa: their possible involvement in chronic rhinosinusitis has been suggested and is one of the main trends in current research. The aim of this study was to investigate whether the presence of any of the 22 currently known staphylococcal exotoxin genes could be correlated with chronic rhinosinusitis. Methodology/Principal Findings We conducted a prospective, multi-centred European study, analysing 93 Staphylococcus aureus positive swabs taken from the middle meatus of patients suffering from chronic rhinosinusitis, with or without nasal polyposis, and controls. Strains were systematically tested for the presence of the 22 currently known exotoxin genes and genotyped according to their agr groups. No direct correlation was observed between chronic rhinosinusitis, with or without nasal polyposis, and either agr groups or the presence of the most studied exotoxins genes (egc, sea, seb, pvl, exfoliatins or tsst-1). However, genes for enterotoxins P and Q were frequently observed in nasal polyposis for the first time, but absent in the control group. The number of exotoxin genes detected was not statistically different among the 3 patient groups. Conclusions/Significance Unlike many previous studies have been suggesting, we did not find any evident correlation between staphylococcal exotoxin genes and the presence or severity of chronic rhinosinusitis with or without nasal polyposis. PMID:20221434

  11. An african-specific functional polymorphism in KCNMB1 shows sex-specific association with asthma severity

    PubMed Central

    Seibold, Max A.; Wang, Bin; Eng, Celeste; Kumar, Gunjan; Beckman, Kenneth B.; Sen, Saunak; Choudhry, Shweta; Meade, Kelley; Lenoir, Michael; Watson, H. Geoffrey; Thyne, Shannon; Williams, L. Keoki; Kumar, Rajesh; Weiss, Kevin B.; Grammer, Leslie C.; Avila, Pedro C.; Schleimer, Robert P.; Burchard, Esteban González; Brenner, Robert

    2008-01-01

    A highly heritable and reproducible measure of asthma severity is baseline pulmonary function. Pulmonary function is largely determined by airway smooth muscle (ASM) tone and contractility. The large conductance, voltage and calcium-activated potassium (BK) channel negatively regulates smooth muscle tone and contraction in ASM. The modulatory subunit of BK channels, the β1-subunit, is critical for proper activation of BK channels in smooth muscle and has shown sex hormone specific regulation. We hypothesized that KCNMB1 genetic variants in African Americans may underlie differences in bronchial smooth muscle tone and thus pulmonary function, possibly in a sex-specific manner. Through resequencing of the KCNMB1 gene we identified several common variants including a novel African-specific coding polymorphism (C818T, R140W). The C818T SNP and four other KCNMB1 variants were genotyped in two independent groups of African American asthmatics (n = 509) and tested for association with the pulmonary function measure – forced expiratory volume (FEV1) % of predicted value. The 818T allele is associated with a clinically significant decline (−13%) in FEV1 in both cohorts of asthmatics among males but not females (Pcombined = 0.0003). Patch clamp electrophysiology studies of the BK channel expressed with the 140Trp variant of the β1-subunit demonstrated significantly reduced channel openings, predicted by the loss of pulmonary function observed. African American male asthmatics carrying the 818T allele (10% of population) are potentially at risk for greater airway obstruction and increased asthma morbidity. Female asthmatics may be insulated from the deleterious effects of the 818T allele by estrogen-mediated upregulation in BK channel activity. PMID:18535015

  12. bioA mutant of Mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs

    PubMed Central

    Kar, Ritika; Nangpal, Prachi; Mathur, Shubhita; Singh, Swati

    2017-01-01

    Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette–Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally. Immunization with MtbΔbioA conferred significant protection in guinea pigs against an aerosol challenge with virulent M. tuberculosis, when compared with the unvaccinated animals. Booster immunization with MtbΔbioA offered no advantage over a single immunization. These experiments demonstrate the vaccinogenic potential of the attenuated M. tuberculosis bioA mutant against tuberculosis. PMID:28658275

  13. bioA mutant of Mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs.

    PubMed

    Kar, Ritika; Nangpal, Prachi; Mathur, Shubhita; Singh, Swati; Tyagi, Anil K

    2017-01-01

    Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette-Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally. Immunization with MtbΔbioA conferred significant protection in guinea pigs against an aerosol challenge with virulent M. tuberculosis, when compared with the unvaccinated animals. Booster immunization with MtbΔbioA offered no advantage over a single immunization. These experiments demonstrate the vaccinogenic potential of the attenuated M. tuberculosis bioA mutant against tuberculosis.

  14. Severe SMA mice show organ impairment that cannot be rescued by therapy with the HDACi JNJ-26481585.

    PubMed

    Schreml, Julia; Riessland, Markus; Paterno, Mario; Garbes, Lutz; Roßbach, Kristina; Ackermann, Bastian; Krämer, Jan; Somers, Eilidh; Parson, Simon H; Heller, Raoul; Berkessel, Albrecht; Sterner-Kock, Anja; Wirth, Brunhilde

    2013-06-01

    Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials. When administered for 64 h at 100 nM, JNJ-26481585 upregulated SMN levels in SMA fibroblast cell lines, including those from non-responders to valproic acid. Oral treatment of Taiwanese SMA mice and control littermates starting at P0 showed no overt extension of lifespan, despite mild improvements in motor abilities and weight progression. Many treated and untreated animals showed a very rapid decline or unexpected sudden death. We performed exploratory autopsy and histological assessment at different disease stages and found consistent abnormalities in the intestine, heart and lung and skeletal muscle vasculature of SMA animals, which were not prevented by JNJ-26481585 treatment. Interestingly, some of these features may be only indirectly caused by α-motoneuron function loss but may be major life-limiting factors in the course of disease. A better understanding of - primary or secondary - non-neuromuscular organ involvement in SMA patients may improve standard of care and may lead to reassessment of how to investigate SMA patients clinically.

  15. Extended-Release Guanfacine Does Not Show a Large Effect on Tic Severity in Children with Chronic Tic Disorders.

    PubMed

    Murphy, Tanya K; Fernandez, Thomas V; Coffey, Barbara J; Rahman, Omar; Gavaletz, Allison; Hanks, Camille E; Tillberg, Caitlin S; Gomez, Laura Ibanez; Sukhodolsky, Denis G; Katsovich, Lily; Scahill, Lawrence

    2017-07-19

    To evaluate the tolerability, safety, and preliminary efficacy of extended-release guanfacine in children with chronic tic disorders, including Tourette's disorder (collectively referred to as CTD). This was a multisite, 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS) total score. Key secondary outcomes included the Improvement item of Clinical Global Impressions-Improvement (CGI-I) scale and the Tic Symptom Self-report (TSSR). Adverse events were monitored at each visit. Thirty-four subjects (23 boys and 11 girls) of ages 6 to 17 years (mean = 11.1 ± 3.1) with CTD were randomly assigned to extended-release guanfacine (n = 16) or placebo (n = 18). At baseline, the mean YGTSS total score was 26.3 ± 6.6 for the guanfacine group versus 27.7 ± 8.7 for the placebo group. Within the guanfacine group (mean final daily dose of 2.6 ± 1.1 mg, n = 14), the mean YGTSS total score declined to 23.6 ± 6.42 [t(15) = 1.84, p = 0.08; effect size = 0.35]. The results were similar in the placebo group with a score of 24.7 ± 10.54 at week 8 [t(17) = 1.83, p = 0.08; effect size = 0.38]. There was no significant difference in the rate of positive response on the CGI-I between the guanfacine group and placebo (19% [3/16] vs. 22% [4/18], p = 1.0). The most common adverse events were fatigue, drowsiness, dry mouth, headache, and irritability. Two subjects in the guanfacine group discontinued early-one because of an adverse event (depressed mood) and one because of lack of efficacy; two subjects in the placebo group discontinued because of lack of efficacy. This pilot study did not confirm a clinically meaningful effect size within the guanfacine group. These results do not support the launch of a larger efficacy trial for tics in children and adolescents with CTD.

  16. ApoA-I mimetics.

    PubMed

    Stoekenbroek, R M; Stroes, E S; Hovingh, G K

    2015-01-01

    A wealth of evidence indicates that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to the risk of cardiovascular disease (CVD). Consequently, HDL-C has been considered a target for therapy in order to reduce the residual CVD burden that remains significant, even after application of current state-of-the-art medical interventions. In recent years, however, a number of clinical trials of therapeutic strategies that increase HDL-C levels failed to show the anticipated beneficial effect on CVD outcomes. As a result, attention has begun to shift toward strategies to improve HDL functionality, rather than levels of HDL-C per se. ApoA-I, the major protein component of HDL, is considered to play an important role in many of the antiatherogenic functions of HDL, most notably reverse cholesterol transport (RCT), and several therapies have been developed to mimic apoA-I function, including administration of apoA-I, mutated variants of apoA-I, and apoA-I mimetic peptides. Based on the potential anti-inflammatory effects, apoA-I mimetics hold promise not only as anti-atherosclerotic therapy but also in other therapeutic areas.

  17. [A case of Charcot-Marie-Tooth disease 1 B with Val 146Phe mutation of myelin protein zero showing a severe clinical phenotype].

    PubMed

    Ohnishi, A; Aoki, A; Yamamoto, T; Tsuji, S

    2000-03-01

    A 15-year-old boy had complaints of progressive gait disturbance and foot deformity. He started to walk at the age of 18 months. Since two years of age, he had noticed unstable gait. He showed evident scoliosis and enlarged great auricular nerves. Moderate to slight degrees of muscular atrophy and weakness of distal upper, and proximal and distal lower limbs were observed. Pes equinovarus deformity of both feet was obvious. Muscle stretch reflexes were absent in both limbs except decreased triceps brachii reflex. Vibratory sensation was decreased severely in the toes and mildly in the fingers. In cerebrospinal fluid, protein was mildly elevated. Median nerve motor conduction velocity was 5.0 m/sec. On sural nerve biopsy, both demyelinated and remyelinated axons and onion-bulbs without hypomyelination were observed. Therefore, the diagnosis of Charcot-Marie-Tooth disease 1 was made. The direct sequencing of the genomic DNA encoding the Po gene revealed a mutant allele, a guanine to thymine substitution of nucleotide position 436, which caused a substitution of phenylalanine for valine at amino acid position 146. This type of Po mutation is different from any type of Po mutation reported in the literature.

  18. The mammalian alcohol dehydrogenase genome shows several gene duplications and gene losses resulting in a large set of different enzymes including pseudoenzymes.

    PubMed

    Östberg, Linus J; Persson, Bengt; Höög, Jan-Olov

    2015-06-05

    Mammalian alcohol dehydrogenase (ADH) is a protein family divided into six classes and the number of known family members is increasing rapidly. Several primate genomes are completely analyzed for the ADH region, where higher primates (human and hominoids) have seven genes of classes ADH1-ADH5. Within the group of non-hominoids apes there have been further duplications and species with more than the typical three isozymic forms for ADH1 are present. In contrast there are few completely analyzed ADH genomes in the non-primate group of mammals, where an additional class has been identified, ADH6, that has been lost during the evolution of primates. In this study 85 mammalian genomes with at least one ADH gene have been compiled. In total more than 500 ADH amino acid sequences were analyzed for patterns that distinguish the different classes. For ADH1-ADH4 intensive investigations have been performed both at the functional and at structural levels. However, a corresponding functional protein to the ADH5 gene, which is found in most ADH genomes, has never been detected. The same is true for ADH6, which is only present in non-primates. The entire mammalian ADH family shows a broad spectrum of gene duplications and gene losses where the numbers differ from six genes (most non-primate mammals) up to ten genes (vole). Included in these sets are examples of pseudogenes and pseudoenzymes.

  19. A new sentinel surveillance system for severe influenza in England shows a shift in age distribution of hospitalised cases in the post-pandemic period.

    PubMed

    Bolotin, Shelly; Pebody, Richard; White, Peter J; McMenamin, James; Perera, Luke; Nguyen-Van-Tam, Jonathan S; Barlow, Thomas; Watson, John M

    2012-01-01

    The World Health Organization and European Centre for Disease Prevention and Control have highlighted the importance of establishing systems to monitor severe influenza. Following the H1N1 (2009) influenza pandemic, a sentinel network of 23 Trusts, the UK Severe Influenza Surveillance System (USISS), was established to monitor hospitalisations due to confirmed seasonal influenza in England. This article presents the results of the first season of operation of USISS in 2010/11. A case was defined as a person hospitalised with confirmed influenza of any type. Weekly aggregate numbers of hospitalised influenza cases, broken down by flu type and level of care, were submitted by participating Trusts. Cases in 2010/11 were compared to cases during the 2009 pandemic in hospitals with available surveillance data for both time periods (n = 19). An unexpected resurgence in seasonal A/H1N1 (2009) influenza activity in England was observed in December 2010 with reports of severe disease. Reported cases over the period of 4 October 2010 to 13 February 2011 were mostly due to influenza A/H1N1 (2009). One thousand and seventy-one cases of influenza A/H1N1 (2009) occurred over this period compared to 409 at the same Trusts over the 2009/10 pandemic period (1 April 2009 to 6 January 2010). Median age of influenza A/H1N1 (2009) cases in 2010/11 was 35 years, compared with 20 years during the pandemic (p = <0.0001). The Health Protection Agency successfully established a sentinel surveillance system for severe influenza in 2010/11, detecting a rise in influenza cases mirroring other surveillance indicators. The data indicate an upward shift in the age-distribution of influenza A/H1N1 (2009) during the 2010/11 influenza season as compared to the 2009/10 pandemic. Systems to enable the ongoing surveillance of severe influenza will be a key component in understanding and responding to the evolving epidemiology of influenza in the post-pandemic era.

  20. Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic syndrome patients with severe neurological symptoms but no changes in conventional MRI.

    PubMed

    Weissenborn, Karin; Bültmann, Eva; Donnerstag, Frank; Giesemann, Anja M; Götz, Friedrich; Worthmann, Hans; Heeren, Meike; Kielstein, Jan; Schwarz, Anke; Lanfermann, Heinrich; Ding, Xiao-Qi

    2013-07-01

    Severe neurological symptoms in Shiga toxin-producing Escherichia coli infection associated hemolytic-uremic syndrome (STEC-HUS) are often accompanied by none or only mild alterations of cerebral magnetic resonance imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal cerebral pathological alterations invisible for conventional MRI. In nine patients with STEC-HUS associated severe neurological symptoms but inconspicuous cerebral MRI findings maps of the parameters T2 relaxation time, relative proton density (PD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were generated. Quantitative values of these parameters were measured at the basal ganglia, thalamus, and white matter of the frontal and parietal lobe and compared to those of nine age- and sex-matched controls. Significant T2 prolongation (p < 0.01) was found in the basal ganglia of all patients compared to controls. PD and ADC were not significantly altered. A significant reduction of FA in patients was seen at caput nuclei caudati (p < 0.01). Prolonged T2 relaxation time indicates cerebral microstructural damages in these patients despite their inconspicuous MRI findings. T2 relaxometry could be used as a complementary tool for the assessment of metabolic-toxic brain syndromes.

  1. Tuberculosis of the spine with severe angular kyphosis: mean 34-year post-operative follow-up shows that prevention is better than salvage.

    PubMed

    Wong, Y W; Samartzis, D; Cheung, K M C; Luk, K

    2017-10-01

    To address the natural history of severe post-tuberculous (TB) kyphosis, with focus upon the long-term neurological outcome, occurrence of restrictive lung disease, and the effect on life expectancy. This is a retrospective clinical review of prospectively collected imaging data based at a single institute. A total of 24 patients of Southern Chinese origin who presented with spinal TB with a mean of 113° of kyphosis (65° to 159°) who fulfilled inclusion criteria were reviewed. Plain radiographs were used to assess the degree of spinal deformity. Myelography, CT and MRI were used when available to assess the integrity of the spinal cord and canal. Patient demographics, age of onset of spinal TB and interventions, types of surgical procedure, intra- and post-operative complications, and neurological status were assessed. All except one of the 24 patients were treated with anti-TB chemotherapy when they were first diagnosed with spinal TB. They subsequently received surgery either for neurological deterioration, or deformity correction in later life. The mean follow-up was 34 years (11 to 59) since these surgical interventions. Some 16 patients (66.7%) suffered from late neurological deterioration at a mean of 26 years (8 to 49) after the initial drug treatment. The causes of neurological deterioration were healed disease in nine patients (56.2%), re-activation in six patients (37.5%) and adjacent level spinal stenosis in one patient (6.3%). The result of surgery was worse in healed disease. Eight patients without neurological deterioration received surgery to correct the kyphosis. The mean correction ranged from 97° to 72°. Three patients who were clinically quiescent with no neurological deterioration were found to have active TB of the spine. Solid fusion was achieved in all cases and no patient suffered from neurological deterioration after 42 years of follow-up. On final follow-up, six patients were noted to have deceased (age range: 47 years to 75 years

  2. A case of diabetic amyotrophy with severe atrophy and weakness of shoulder girdle muscles showing good response to intravenous immune globulin.

    PubMed

    Wada, Yuko; Yanagihara, Chie; Nishimura, Yo; Oka, Nobuyuki

    2007-01-01

    A 45-year-old man with insulin-dependent diabetic mellitus developed progressive asymmetrical weakness and atrophy of both shoulder girdle muscles within 1 year. In the last month, he also developed slight weakness of both thighs. Neuropathology of the sural nerve showed an axonal degeneration and perivascular inflammation and electromyography revealed neurogenic changes. Because of a diagnosis of suspected diabetic amyotrophy, intravenous immunoglobulin was administered. This treatment produced marked improvement. Physicians should take into account the possibility of diabetic amyotrophy in patients with diabetic mellitus showing primary involvement of shoulder girdle muscles marked by weakness and atrophy.

  3. Double-blind placebo-controlled challenge showed that peanut oral immunotherapy was effective for severe allergy without negative effects on airway inflammation.

    PubMed

    Kukkonen, Anna Kaarina; Uotila, Riikka; Malmberg, Leo Pekka; Pelkonen, Anna Susanna; Mäkelä, Mika Juhani

    2017-02-01

    This study examined the efficacy and the safety of peanut oral immunotherapy (OIT). We recruited 60 patients aged six years to 18 years who had a moderate-to-severe reaction to a double-blind placebo-controlled peanut challenge: 39 received OIT during an eight-month build-up phase and maintenance phase and 21 controls avoided peanuts. We measured specific immunoglobulin E and G4 (IgE and IgG4) to peanuts and to Ara h 1, 2, 3, 8 and 9 and monitored adverse events, bronchial hyper-responsiveness (BHR) to methacholine and fractional concentrations of exhaled nitric oxide (FeNO). The median follow-up period was 30 months. Most (85%) of the OIT patients passed the build-up phase and 67% tolerated 5 g of peanuts during the post-treatment challenge. No controls were desensitised, with a risk ratio of 29 and 95% confidence interval of 1.9-455. During OIT, IgE to peanut, Ara h 1, 2 and 3 decreased and IgG4 increased. Consuming peanuts had no harmful effects on BHR or FeNO. The annual incidence rate of emergency visits during the follow-up period was 11% or 3.0 per 10 000 patient-days. Peanut OIT was efficacious in severe allergies without negative effects on airway inflammation, but unpredictable long-term reactions might occur. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Molecular Evidence for Occurrence of Tomato leaf curl New Delhi virus in Ash Gourd (Benincasa hispida) Germplasm Showing a Severe Yellow Stunt Disease in India.

    PubMed

    Roy, Anirban; Spoorthi, P; Panwar, G; Bag, Manas Kumar; Prasad, T V; Kumar, Gunjeet; Gangopadhyay, K K; Dutta, M

    2013-06-01

    An evaluation of 70 accessions of ash gourd germplasm grown at National Bureau of Plant Genetic Resources, New Delhi, India during Kharif season (2010) showed natural occurrence of a yellow stunt disease in three accessions (IC554690, IC036330 and Pusa Ujjwal). A set of begomovirus specific primers used in PCR gave expected amplicon from all the symptomatic plants; however no betasatellite was detected. Complete genome of the begomovirus (DNA-A and DNA-B), amplified through rolling circle amplification, was cloned and sequenced. The begomovirus under study shared high sequence identities to different isolates of Tomato leaf curl New Delhi virus (ToLCNDV) and clustered with them. Among those isolates, the DNA-A and DNA-B of the present begomovirus isolate showed highest 99.6 and 96.8 % sequence identities, respectively with an isolate reported on pumpkin from India (DNA-A: AM286433, DNA-B: AM286435). Based on the sequence analysis, the begomovirus obtained from ash gourd was considered as an isolate of ToLCNDV. Thus, the present findings constitute the first report of occurrence of a new yellow stunt disease in ash gourd from India and demonstrated the association of ToLCNDV with the symptomatic samples. Occurrence of ToLCNDV in ash gourd germplasm not only adds up a new cucurbitaceous host of this virus but also raises the concern about the perpetuation of this virus in absence of its main host tomato and thus has an epidemiological relevance for understanding the rapid spread of this virus in tomato and other hosts in Indian sub-continent.

  5. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  6. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  7. Show Code.

    PubMed

    Shalev, Daniel

    2017-01-01

    "Let's get one thing straight: there is no such thing as a show code," my attending asserted, pausing for effect. "You either try to resuscitate, or you don't. None of this halfway junk." He spoke so loudly that the two off-service consultants huddled at computers at the end of the unit looked up… We did four rounds of compressions and pushed epinephrine twice. It was not a long code. We did good, strong compressions and coded this man in earnest until the end. Toward the final round, though, as I stepped up to do compressions, my attending looked at me in a deep way. It was a look in between willing me as some object under his command and revealing to me everything that lay within his brash, confident surface but could not be spoken. © 2017 The Hastings Center.

  8. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  9. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  10. Double negative (IgG+IgD-CD27-) B cells are increased in a cohort of moderate-severe Alzheimer's disease patients and show a pro-inflammatory trafficking receptor phenotype.

    PubMed

    Bulati, Matteo; Buffa, Silvio; Martorana, Adriana; Gervasi, Francesco; Camarda, Cecilia; Azzarello, Delia Maria; Monastero, Roberto; Caruso, Calogero; Colonna-Romano, Giuseppina

    2015-01-01

    Alzheimer's disease (AD) is a progressive, irreversible, and debilitating disease for which no effective preventive or disease modifying therapies or treatments have so far been detected. The crucial step in AD pathogenesis is the production of amyloid-β42 peptide, which causes chronic inflammation. Activated cells in the central nervous system (CNS) produce pro-inflammatory mediators that lead to the recruitment of myeloid or lymphocytic cells. As a consequence, the communication between the CNS and peripheral blood of AD subjects could influence the lymphocyte distribution and/or the expression of phenotypic markers. In the present paper, we show a significant decrease in total CD19+ B lymphocytes and a remodeling of the B cell subpopulations in moderate-severe AD patients, compared with their coeval healthy controls and mild AD subjects. In particular, we report a significant reduction in naïve B cells (IgD+CD27-) and a simultaneous increase in double negative (DN, IgD-CD27-) memory B lymphocytes. We have also evaluated the expression of the pro-inflammatory chemokine receptors CCR6 and CCR7 in total and naïve/memory B cells from mild and moderate-severe AD patients, with the aim to detect a possible relationship between the trafficking profile and the stage of the disease. Our results demonstrate that both the amount and the trafficking profile of B cells are related to the severity of AD. The results discussed in this paper suggest a well-selected antibody panel should be used as an additional test for the identification of early AD.

  11. [Value of serial CT scanning and intracranial pressure monitoring for detecting new intracranial mass effect in severe head injury patients showing lesions type I-II in the initial CT scan].

    PubMed

    Lobato, R D; Alen, J F; Perez-Nuñez, A; Alday, R; Gómez, P A; Pascual, B; Lagares, A; Miranda, P; Arrese, I; Kaen, A

    2005-06-01

    To determine the incidence of pathological and intracranial pressure (ICP) changes during the acute posttraumatic period in severe head injury patients presenting with lesions Types I-II (TCDB classification) in the admission CT scan with the aim of defining the most appropriate strategy of sequential CT scanning and ICP monitoring for detecting new intra-cranial mass effect and improving the final outcome. 56 patients (ages 15-80 years) consecutively admitted during a 2 years period were included. All had the initial CT scan < 24 hours after injury (mean interval = 150 min), several CT controls within the first days of the course and ICP monitoring after admission. Different epidemiological, clinical and radiological variables were recorded and deterioration defined as the development of sustained ICP over 20 mmHg requiring aggressive medical and/or surgical treatment was considered the dependent variable. Uni and multivariate analyses were made for determining the correlation between different parameters and the occurrence of deterioration and the final outcome as assessed with the GOS. The mean GCS score was 5 and 37% of the patients showed pupillary changes; 52.3% had peritraumatic hypotension-hypoxemia, 16.1% anemia and 12.3% coagulation changes. 50% of the patients showed petechial hemorrhages in the white matter or the brainstem, 66% SAH, 40% HIV, 39.3% brain contusion and 21.4% small extraaxial hematomas. 57.1% of the patients showed CT changes through the acute post-traumatic period consisting of new contusion (26.8% of the cases), growing of previous contusion (68.2%) or previous extraaxial hematoma (10.7%), and generalized brain swelling (10.7%). 64.9% of the patients made a favourable and 35.7% an unfavourable outcome. Overall, 27 (48.9%) patients developed deterioration, 21 (37.5%) with concurrent CT changes and 6 (10.7%) without new pathology as seen by the CT control. The remaining 29 (51.7%) patients in this series did not develop deterioration in

  12. Identification of proteins from 4200-year-old skin and muscle tissue biopsies from ancient Egyptian mummies of the first intermediate period shows evidence of acute inflammation and severe immune response.

    PubMed

    Jones, Jana; Mirzaei, Mehdi; Ravishankar, Prathiba; Xavier, Dylan; Lim, Do Seon; Shin, Dong Hoon; Bianucci, Raffaella; Haynes, Paul A

    2016-10-28

    We performed proteomics analysis on four skin and one muscle tissue samples taken from three ancient Egyptian mummies of the first intermediate period, approximately 4200 years old. The mummies were first dated by radiocarbon dating of the accompany-\\break ing textiles, and morphologically examined by scanning electron microscopy of additional skin samples. Proteins were extracted, separated on SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) gels, and in-gel digested with trypsin. The resulting peptides were analysed using nanoflow high-performance liquid chromatography-mass spectrometry. We identified a total of 230 unique proteins from the five samples, which consisted of 132 unique protein identifications. We found a large number of collagens, which was confirmed by our microscopy data, and is in agreement with previous studies showing that collagens are very long-lived. As expected, we also found a large number of keratins. We identified numerous proteins that provide evidence of activation of the innate immunity system in two of the mummies, one of which also contained proteins indicating severe tissue inflammation, possibly indicative of an infection that we can speculate may have been related to the cause of death.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Author(s).

  13. The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids.

    PubMed

    van Middelkoop, M; Arden, N K; Atchia, I; Birrell, F; Chao, J; Rezende, M U; Lambert, R G W; Ravaud, P; Bijlsma, J W; Doherty, M; Dziedzic, K S; Lohmander, L S; McAlindon, T E; Zhang, W; Bierma-Zeinstra, S M A

    2016-07-01

    To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (≥70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study. Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid- and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Radar Shows Evidence of Seas

    NASA Image and Video Library

    2007-03-13

    This movie, comprised of several detailed images taken by Cassini radar instrument, shows bodies of liquid near Titan north pole. These images show that many of the features commonly associated with lakes on Earth

  15. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show.

  16. Human Apolipoprotein A-I Natural Variants: Molecular Mechanisms Underlying Amyloidogenic Propensity

    PubMed Central

    Ramella, Nahuel A.; Schinella, Guillermo R.; Ferreira, Sergio T.; Prieto, Eduardo D.; Vela, María E.; Ríos, José Luis

    2012-01-01

    Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe atherosclerosis. Results showed that both variants share common structural properties including decreased stability compared to Wt apoA-I and a more flexible structure that gives rise to formation of partially folded states. Interestingly, however, distinct features appear to determine their pathogenic mechanisms. ApoA-ILys107-0 has an increased propensity to aggregate at physiological pH and in a pro-inflammatory microenvironment than Wt apoA-I, whereas apoA-IGly26Arg elicited macrophage activation, thus stimulating local chronic inflammation. Our results strongly suggest that some natural mutations in apoA-I variants elicit protein tendency to aggregate, but in addition the specific interaction of different variants with macrophages may contribute to cellular stress and toxicity in hereditary amyloidosis. PMID:22952757

  17. The promise of apolipoprotein A-I mimetics.

    PubMed

    Mendez, Armando J

    2010-04-01

    Synthetic high-density lipoprotein (HDL) and apolipoprotein (apo) A-I mimetic peptides emulate many of the atheroprotective biological functions attributed to HDL and can modify atherosclerotic disease processes. Administration of these agents as HDL replacement or modifying therapy has tremendous potential of providing new treatments for cardiovascular disease. Progress in the understanding of these agents is discussed in this review. Prospective, observational, and interventional studies have convincingly demonstrated that elevated serum levels of high-density lipoprotein-cholesterol (HDL-C) are associated with reduced risk for coronary heart disease (CHD). Although traditional pharmacological agents have shown modest utility in raising HDL levels and reducing CHD risk, use of HDL and apo A-I mimetics provides novel therapies to not only increase HDL levels, but to also influence HDL functionality. Evidence developed over the last several years has identified a number of pathways affected by synthetic HDL and apoA-I mimetic peptides, including enhancing reverse cholesterol transport and reducing oxidation and inflammation that directly influence the progression and regression of atherosclerotic disease. Clinical trials of relatively short-term synthetic HDL infusion into patients with CHD demonstrate beneficial effects. Use of apo A-I mimetic peptides could potentially overcome some of the limitations associated with use of the intact apo. Studies to establish the most efficacious peptides, optimal dosing regimens, and routes of administration are needed. Use of apo A-I mimetic peptides shows great promise as a therapeutic modality for HDL replacement and enhancing HDL function in treatment of patients with CHD.

  18. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  19. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  20. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  1. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  2. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave

  3. HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

    PubMed

    Borja, Mark S; Zhao, Lei; Hammerson, Bradley; Tang, Chongren; Yang, Richard; Carson, Nancy; Fernando, Gayani; Liu, Xiaoqin; Budamagunta, Madhu S; Genest, Jacques; Shearer, Gregory C; Duclos, Franck; Oda, Michael N

    2013-01-01

    High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

  4. HDL-apoA-I Exchange: Rapid Detection and Association with Atherosclerosis

    PubMed Central

    Borja, Mark S.; Zhao, Lei; Hammerson, Bradley; Tang, Chongren; Yang, Richard; Carson, Nancy; Fernando, Gayani; Liu, Xiaoqin; Budamagunta, Madhu S.; Genest, Jacques; Shearer, Gregory C.; Duclos, Franck; Oda, Michael N.

    2013-01-01

    High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease. PMID:24015188

  5. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  6. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  7. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  8. Chemistry Game Shows

    NASA Astrophysics Data System (ADS)

    Campbell, Susan; Muzyka, Jennifer

    2002-04-01

    We present a technological improvement to the use of game shows to help students review for tests. Our approach uses HTML files interpreted with a browser on a computer attached to an LCD projector. The HTML files can be easily modified for use of the game in a variety of courses.

  9. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  10. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  11. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  12. Talk Show Science.

    ERIC Educational Resources Information Center

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  13. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  14. The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein.

    PubMed

    Kozyraki, R; Fyfe, J; Kristiansen, M; Gerdes, C; Jacobsen, C; Cui, S; Christensen, E I; Aminoff, M; de la Chapelle, A; Krahe, R; Verroust, P J; Moestrup, S K

    1999-06-01

    Cubilin is the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. However, several lines of evidence, including a high expression in kidney and yolk sac, indicate it may have additional functions. We isolated apolipoprotein A-I (apoA-I), the main protein of high-density lipoprotein (HDL), using cubilin affinity chromatography. Surface plasmon resonance analysis demonstrated a high-affinity binding of apoA-I and HDL to cubilin, and cubilin-expressing yolk sac cells showed efficient 125I-HDL endocytosis that could be inhibited by IgG antibodies against apoA-I and cubilin. The physiological relevance of the cubilin-apoA-I interaction was further emphasized by urinary apoA-I loss in some known cases of functional cubilin deficiency. Therefore, cubilin is a receptor in epithelial apoA-I/HDL metabolism.

  15. Mars Slide Show

    NASA Technical Reports Server (NTRS)

    2006-01-01

    15 September 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a landslide that occurred off of a steep slope in Tithonium Chasma, part of the vast Valles Marineris trough system.

    Location near: 4.8oS, 84.6oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Autumn

  16. Expression and purification of recombinant apolipoprotein A-I Zaragoza (L144R) and formation of reconstituted HDL particles.

    PubMed

    Fiddyment, Sarah; Barceló-Batllori, Sílvia; Pocoví, Miguel; García-Otín, Angel-Luis

    2011-11-01

    Apolipoprotein A-I Zaragoza (L144R) (apo A-I Z), has been associated with severe hypoalphalipoproteinemia and an enhanced effect of high density lipoprotein (HDL) reverse cholesterol transport. In order to perform further studies with this protein we have optimized an expression and purification method of recombinant wild-type apo A-I and apo A-I Z and produced mimetic HDL particles with each protein. An pET-45 expression system was used to produce N-terminal His-tagged apo A-I, wild-type or mutant, in Escherichia coli BL21 (DE3) which was subsequently purified by affinity chromatography in non-denaturing conditions. HDL particles were generated via a modified sodium cholate method. Expression and purification of both proteins was verified by SDS-PAGE, MALDI-TOF MS and immunochemical procedures. Yield was 30mg of purified protein (94% purity) per liter of culture. The reconstituted HDL particles checked via non-denaturing PAGE showed high homogeneity in their size when reconstituted both with wild-type apo A-I and apo A-I Z. An optimized system for the expression and purification of wild-type apo A-I and apo A-I Z with high yield and purity grade has been achieved, in addition to their use in reconstituted HDL particles, as a basis for further studies.

  17. Apolipoprotein A-I modulates regulatory T cells in autoimmune LDLr-/-, ApoA-I-/- mice.

    PubMed

    Wilhelm, Ashley J; Zabalawi, Manal; Owen, John S; Shah, Dharika; Grayson, Jason M; Major, Amy S; Bhat, Shaila; Gibbs, Dwayne P; Thomas, Michael J; Sorci-Thomas, Mary G

    2010-11-12

    The immune system is complex, with multiple layers of regulation that serve to prevent the production of self-antigens. One layer of regulation involves regulatory T cells (Tregs) that play an essential role in maintaining peripheral self-tolerance. Patients with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis have decreased levels of HDL, suggesting that apoA-I concentrations may be important in preventing autoimmunity and the loss of self-tolerance. In published studies, hypercholesterolemic mice lacking HDL apoA-I or LDLr(-/-), apoA-I(-/-) (DKO), exhibit characteristics of autoimmunity in response to an atherogenic diet. This phenotype is characterized by enlarged cholesterol-enriched lymph nodes (LNs), as well as increased T cell activation, proliferation, and the production of autoantibodies in plasma. In this study, we investigated whether treatment of mice with lipid-free apoA-I could attenuate the autoimmune phenotype. To do this, DKO mice were first fed an atherogenic diet containing 0.1% cholesterol, 10% fat for 6 weeks, after which treatment with apoA-I was begun. Subcutaneous injections of 500 μg of lipid-free apoA-I was administered every 48 h during the treatment phase. These and control mice were maintained for an additional 6 weeks on the diet. At the end of the 12-week study, DKO mice showed decreased numbers of LN immune cells, whereas Tregs were proportionately increased. Accompanying this increase in Tregs was a decrease in the percentage of effector/effector memory T cells. Furthermore, lipid accumulation in LN and skin was reduced. These results suggest that treatment with apoA-I reduces inflammation in DKO mice by augmenting the effectiveness of the LN Treg response.

  18. XMM on show

    NASA Astrophysics Data System (ADS)

    1998-01-01

    A unique opportunity for journalists and cameramen to view Europe's next scientific satellite, XMM, will be provided at ESA/ESTEC, Noordwijk, the Netherlands on Tuesday 10 February at 10:00 a.m. On show will be the full-size development version of XMM which has completed engineering tests. Press representatives will be permitted to inspect it and take pictures at close quarters. Robert Lainé, the XMM project manager, and Fred Jansen, the XMM project scientist will present the spacecraft and mission. Roger Bonnet, Director of the ESA Science programme will present Horizons 2000, the future ESA Science programme. After the presentations they will be available to answer questions. Due for launch in 1999, XMM is an unprecedented space observatory for X-ray astronomy, with far greater sensitivity than any previous X-ray mission. It is also ESA's largest scientific spacecraft -- almost 11 metres long and with a mass of nearly 4 tonnes.

  19. Fructated apolipoprotein A-I exacerbates cellular senescence in human umbilical vein endothelial cells accompanied by impaired insulin secretion activity and embryo toxicity.

    PubMed

    Park, Ki-Hoon; Kim, Jae-Yong; Choi, Inho; Kim, Jae-Ryong; Won, Kyu Chang; Cho, Kyung-Hyun

    2016-08-01

    Glycation of apolipoproteins is a major feature of the production of dysfunctional high-density lipoprotein (HDL), which is associated with the incidence of several metabolic diseases such as coronary artery disease and diabetes. In this report, fructated apoA-I (fA-I) induced by fructose treatment showed a covalently multimerized band without cross-linking, and lysine residues were irreversibly modified to prevent crosslinking. Using pancreatic β-cells, insulin secretion was impaired by fA-I in the lipid-free and reconstituted HDL (rHDL) states, by up to 35%, and 40%, respectively, under hyperglycemic conditions (25 mmol/L glucose). Treatment of human umbilical vein endothelial cells (HUVECs) with fA-I and HDL from elderly patients caused a 1.8-fold and 1.5-fold increased cellular senescence, respectively, along with increased lysosomal enlargement. In the lipid-free and rHDL states, fA-I increased embryo death by 1.5-fold and 2.5-fold, respectively, along with the production of oxidized species. Furthermore, rHDL containing fA-I (fA-I-rHDL) showed a higher isoelectric point (pI, approximately 8.5), whereas rHDL containing nA-I (nA-I-rHDL) showed a narrow band range with lower pI (around 8.0) as well as a much smaller particle size than that of nA-I-rHDL. In conclusion, fructose-mediated apoA-I fructation resulted in the severe loss of several beneficial functions of apoA-I and HDL, including anti-senescence and insulin secretion activities, accompanied with increased susceptibility to protein degradation and structural modification.

  20. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

    PubMed Central

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M.; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F.; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M.; Reddy, Srinivasa T.; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2016-01-01

    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification. PMID:27808249

  1. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer.

    PubMed

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M; Reddy, Srinivasa T; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2016-11-03

    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.

  2. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre.

  3. Severe Weather

    ERIC Educational Resources Information Center

    Forde, Evan B.

    2004-01-01

    Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. This article deals with a poster entitled, "Severe Weather," that has been created by NOAA to help educate the public about hazardous weather conditions. The four types of severe weather highlighted in…

  4. Severe Weather

    ERIC Educational Resources Information Center

    Forde, Evan B.

    2004-01-01

    Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. This month's insert, Severe Weather, has been created by NOAA to help educate the public about hazardous weather conditions. The four types of severe weather highlighted in this poster are hurricanes,…

  5. Severe Weather

    ERIC Educational Resources Information Center

    Forde, Evan B.

    2004-01-01

    Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. This article deals with a poster entitled, "Severe Weather," that has been created by NOAA to help educate the public about hazardous weather conditions. The four types of severe weather highlighted in…

  6. Severe Weather

    ERIC Educational Resources Information Center

    Forde, Evan B.

    2004-01-01

    Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. This month's insert, Severe Weather, has been created by NOAA to help educate the public about hazardous weather conditions. The four types of severe weather highlighted in this poster are hurricanes,…

  7. "Show me" bioethics and politics.

    PubMed

    Christopher, Myra J

    2007-10-01

    Missouri, the "Show Me State," has become the epicenter of several important national public policy debates, including abortion rights, the right to choose and refuse medical treatment, and, most recently, early stem cell research. In this environment, the Center for Practical Bioethics (formerly, Midwest Bioethics Center) emerged and grew. The Center's role in these "cultural wars" is not to advocate for a particular position but to provide well researched and objective information, perspective, and advocacy for the ethical justification of policy positions; and to serve as a neutral convener and provider of a public forum for discussion. In this article, the Center's work on early stem cell research is a case study through which to argue that not only the Center, but also the field of bioethics has a critical role in the politics of public health policy.

  8. Sever's Disease

    MedlinePlus

    ... good flexibility while your child is growing. The stretching exercises pictured in the treatment section can lower ... your child has already recovered from Sever's disease, stretching and putting ice on the heel after activity ...

  9. FOXO1 and LXRα downregulate the apolipoprotein A-I gene expression during hydrogen peroxide-induced oxidative stress in HepG2 cells.

    PubMed

    Shavva, Vladimir S; Bogomolova, Alexandra M; Nikitin, Artemy A; Dizhe, Ella B; Oleinikova, Galina N; Lapikov, Ivan A; Tanyanskiy, Dmitry A; Perevozchikov, Andrej P; Orlov, Sergey V

    2017-01-01

    Reactive oxygen species damage various cell components including DNA, proteins, and lipids, and these impairments could be a reason for severe human diseases including atherosclerosis. Forkhead box O1 (FOXO1), an important metabolic transcription factor, upregulates antioxidant and proapoptotic genes during oxidative stress. Apolipoprotein A-I (ApoA-I) forms high density lipoprotein (HDL) particles that are responsible for cholesterol transfer from peripheral tissues to liver for removal in bile in vertebrates. The main sources for plasma ApoA-I in mammals are liver and jejunum. Hepatic apoA-I transcription depends on a multitude of metabolic transcription factors. We demonstrate that ApoA-I synthesis and secretion are decreased during H2O2-induced oxidative stress in human hepatoma cell line HepG2. Here, we first show that FOXO1 binds to site B of apoA-I hepatic enhancer and downregulates apoA-I gene activity in HepG2 cells. Moreover, FOXO1 and LXRα transcription factors participate in H2O2-triggered downregulation of apoA-I gene together with Src, JNK, p38, and AMPK kinase cascades. Mutations of sites B or C as well as the administration of siRNAs against FOXO1 or LXRα to HepG2 cells abolished the hydrogen peroxide-mediated suppression of apoA-I gene.

  10. Casimir experiments showing saturation effects

    SciTech Connect

    Sernelius, Bo E.

    2009-10-15

    We address several different Casimir experiments where theory and experiment disagree. First out is the classical Casimir force measurement between two metal half spaces; here both in the form of the torsion pendulum experiment by Lamoreaux and in the form of the Casimir pressure measurement between a gold sphere and a gold plate as performed by Decca et al.; theory predicts a large negative thermal correction, absent in the high precision experiments. The third experiment is the measurement of the Casimir force between a metal plate and a laser irradiated semiconductor membrane as performed by Chen et al.; the change in force with laser intensity is larger than predicted by theory. The fourth experiment is the measurement of the Casimir force between an atom and a wall in the form of the measurement by Obrecht et al. of the change in oscillation frequency of a {sup 87}Rb Bose-Einstein condensate trapped to a fused silica wall; the change is smaller than predicted by theory. We show that saturation effects can explain the discrepancies between theory and experiment observed in all these cases.

  11. Interaction of human apolipoprotein A-I with model membranes exhibiting lipid domains.

    PubMed

    Arnulphi, Cristina; Sánchez, Susana A; Tricerri, M Alejandra; Gratton, Enrico; Jonas, Ana

    2005-07-01

    Several mechanisms for cell cholesterol efflux have been proposed, including membrane microsolubilization, suggesting that the existence of specific domains could enhance the transfer of lipids to apolipoproteins. In this work isothermal titration calorimetry, circular dichroism spectroscopy, and two-photon microscopy are used to study the interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) of 1-palmitoyl, 2-oleoyl phosphatidylcholine (POPC) and sphingomyelin (SM), with and without cholesterol. Below 30 degrees C the calorimetric results show that apoA-I interaction with POPC/SM SUVs produces an exothermic reaction, characterized as nonclassical hydrophobic binding. The heat capacity change (DeltaCp degrees ) is small and positive, whereas it was larger and negative for pure POPC bilayers, in the absence of SM. Inclusion of cholesterol in the membranes induces changes in the observed thermodynamic pattern of binding and counteracts the formation of alpha-helices in the protein. Above 30 degrees C the reactions are endothermic. Giant unilamellar vesicles (GUVs) of identical composition to the SUVs, and two-photon fluorescence microscopy techniques, were utilized to further characterize the interaction. Fluorescence imaging of the GUVs indicates coexistence of lipid domains under 30 degrees C. Binding experiments and Laurdan generalized-polarization measurements suggest that there is no preferential binding of the labeled apoA-I to any particular domain. Changes in the content of alpha-helix, binding, and fluidity data are discussed in the framework of the thermodynamic parameters.

  12. [Severe asthma].

    PubMed

    González, Claudio D

    2016-01-01

    The objectives of this work were to investigate the frequency of severe asthma (SA) according to WHO definition and to compare SA patients' characteristics with those of non-severe asthma (NSA); secondly, to investigate the level of control reached throughout a period of regular treatment. Between 1-1-2005 and 12-31-2014, 471 medical records from patients with bronchial asthma assisted in Buenos Aires City were analyzed. SA frequency was 40.1% (189/471), being significantly higher among patients from the public health system (47.7%, 108/226 vs. 33%, 81/245, p = 0.001). SA patients were older than NSA ones (51.3 ± 17.4 vs. 42.6 ± 17.1 years, p = 0.000), presented longer time since onset of the disease (median 30 vs. 20 years, p = 0.000), lower educational levels (secondary level or higher 41.7% vs. 58.1%, p = 0.000), lower frequency of rhinitis (47% vs. 60.6%, p = 0.004), more severe levels of airway obstruction (FEV% 50.2 ± 13.7 vs. 77.7 ± 12.4, p = 0.000), more frequent antecedents of Near Fatal Asthma (11.1% vs. 2.8%, p = 0.000), higher levels of serum IgE (median of 410 vs. 279 UI/l, p = 0.01) and higher demand of systemic steroids requirements and hospitalizations (68.7% vs. 50.7%, p = 0.000 and 37.5% vs. 15.9%, p = 0.000, respectively). A 30.6% of SA patients (58/189) reached a follow-up period of 12 months, 13 (22.5%) of whom reached the controlled asthma level. The frequency of SA found seems to be considerable. Multicenter studies to investigate the levels of control reached by SA patients with access to proper treatment are recommended.

  13. ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I (Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of Extracellular Cholesterol Microdomains Deposited by Macrophages.

    PubMed

    Jin, Xueting; Sviridov, Denis; Liu, Ying; Vaisman, Boris; Addadi, Lia; Remaley, Alan T; Kruth, Howard S

    2016-12-01

    We examined the function of ABCA1 (ATP-binding cassette transporter A1) in ApoA-I (apolipoprotein A-I) mobilization of cholesterol microdomains deposited into the extracellular matrix by cholesterol-enriched macrophages. We have also determined whether an ApoA-I mimetic peptide without and with complexing to sphingomyelin can mobilize macrophage-deposited cholesterol microdomains. Extracellular cholesterol microdomains deposited by cholesterol-enriched macrophages were detected with a monoclonal antibody, 58B1. ApoA-I and an ApoA-I mimetic peptide 5A mobilized cholesterol microdomains deposited by ABCA1(+/+) macrophages but not by ABCA1(-/-) macrophages. In contrast, ApoA-I mimetic peptide 5A complexed with sphingomyelin could mobilize cholesterol microdomains deposited by ABCA1(-/-) macrophages. Our findings show that a unique pool of extracellular cholesterol microdomains deposited by macrophages can be mobilized by both ApoA-I and an ApoA-I mimetic peptide but that mobilization depends on macrophage ABCA1. It is known that ABCA1 complexes ApoA-I and ApoA-I mimetic peptide with phospholipid, a cholesterol-solubilizing agent, explaining the requirement for ABCA1 in extracellular cholesterol microdomain mobilization. Importantly, ApoA-I mimetic peptide already complexed with phospholipid can mobilize macrophage-deposited extracellular cholesterol microdomains even in the absence of ABCA1. © 2016 American Heart Association, Inc.

  14. Severe pneumonia.

    PubMed

    Harvey, J

    1982-03-01

    The successful management of severe pneumonia involves a logical approach to antibiotic therapy, based on selecting drugs active against the most likely pathogen in each individual case while awaiting possible identification of an organism. In patients who deteriorate, more invasive diagnostic procedures should be considered in combination with broader-spectrum antibiotic treatment. Controlled oxygen therapy monitored by arterial blood-gas tension measurements is essential and mechanical ventilation may be indicated in some cases. Other measures including physiotherapy, fluid replacement, and the relief of pleuritic pain should not be forgotten.

  15. Carboxyl-Terminal Cleavage of Apolipoprotein A-I by Human Mast Cell Chymase Impairs Its Anti-Inflammatory Properties.

    PubMed

    Nguyen, Su Duy; Maaninka, Katariina; Lappalainen, Jani; Nurmi, Katariina; Metso, Jari; Öörni, Katariina; Navab, Mohamad; Fogelman, Alan M; Jauhiainen, Matti; Lee-Rueckert, Miriam; Kovanen, Petri T

    2016-02-01

    Apolipoprotein A-I (apoA-I) has been shown to possess several atheroprotective functions, including inhibition of inflammation. Protease-secreting activated mast cells reside in human atherosclerotic lesions. Here we investigated the effects of the neutral proteases released by activated mast cells on the anti-inflammatory properties of apoA-I. Activation of human mast cells triggered the release of granule-associated proteases chymase, tryptase, cathepsin G, carboxypeptidase A, and granzyme B. Among them, chymase cleaved apoA-I with the greatest efficiency and generated C-terminally truncated apoA-I, which failed to bind with high affinity to human coronary artery endothelial cells. In tumor necrosis factor-α-activated human coronary artery endothelial cells, the chymase-cleaved apoA-I was unable to suppress nuclear factor-κB-dependent upregulation of vascular cell adhesion molecule-1 (VCAM-1) and to block THP-1 cells from adhering to and transmigrating across the human coronary artery endothelial cells. Chymase-cleaved apoA-I also had an impaired ability to downregulate the expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 in lipopolysaccharide-activated GM-CSF (granulocyte-macrophage colony-stimulating factor)- and M-CSF (macrophage colony-stimulating factor)-differentiated human macrophage foam cells and to inhibit reactive oxygen species formation in PMA (phorbol 12-myristate 13-acetate)-activated human neutrophils. Importantly, chymase-cleaved apoA-I showed reduced ability to inhibit lipopolysaccharide-induced inflammation in vivo in mice. Treatment with chymase blocked the ability of the apoA-I mimetic peptide L-4F, but not of the protease-resistant D-4F, to inhibit proinflammatory gene expression in activated human coronary artery endothelial cells and macrophage foam cells and to prevent reactive oxygen species formation in activated neutrophils. The findings identify C-terminal cleavage of apoA-I by human mast

  16. Carboxyl-Terminal Cleavage of Apolipoprotein A-I by Human Mast Cell Chymase Impairs Its Anti-Inflammatory Properties

    PubMed Central

    Nguyen, Su Duy; Maaninka, Katariina; Lappalainen, Jani; Nurmi, Katariina; Metso, Jari; Öörni, Katariina; Navab, Mohamad; Fogelman, Alan M.; Jauhiainen, Matti; Lee-Rueckert, Miriam

    2016-01-01

    Objective— Apolipoprotein A-I (apoA-I) has been shown to possess several atheroprotective functions, including inhibition of inflammation. Protease-secreting activated mast cells reside in human atherosclerotic lesions. Here we investigated the effects of the neutral proteases released by activated mast cells on the anti-inflammatory properties of apoA-I. Approach and Results— Activation of human mast cells triggered the release of granule-associated proteases chymase, tryptase, cathepsin G, carboxypeptidase A, and granzyme B. Among them, chymase cleaved apoA-I with the greatest efficiency and generated C-terminally truncated apoA-I, which failed to bind with high affinity to human coronary artery endothelial cells. In tumor necrosis factor-α–activated human coronary artery endothelial cells, the chymase-cleaved apoA-I was unable to suppress nuclear factor-κB–dependent upregulation of vascular cell adhesion molecule-1 (VCAM-1) and to block THP-1 cells from adhering to and transmigrating across the human coronary artery endothelial cells. Chymase-cleaved apoA-I also had an impaired ability to downregulate the expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 in lipopolysaccharide-activated GM-CSF (granulocyte-macrophage colony-stimulating factor)– and M-CSF (macrophage colony-stimulating factor)–differentiated human macrophage foam cells and to inhibit reactive oxygen species formation in PMA (phorbol 12-myristate 13-acetate)–activated human neutrophils. Importantly, chymase-cleaved apoA-I showed reduced ability to inhibit lipopolysaccharide-induced inflammation in vivo in mice. Treatment with chymase blocked the ability of the apoA-I mimetic peptide L-4F, but not of the protease-resistant D-4F, to inhibit proinflammatory gene expression in activated human coronary artery endothelial cells and macrophage foam cells and to prevent reactive oxygen species formation in activated neutrophils. Conclusions— The

  17. Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis

    PubMed Central

    Getz, Godfrey S; Reardon, Catherine A

    2011-01-01

    Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans. PMID:22096372

  18. 15. Detail showing lower chord pinconnected to vertical member, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Detail showing lower chord pin-connected to vertical member, showing floor beam riveted to extension of vertical member below pin-connection, and showing brackets supporting cantilevered sidewalk. View to southwest. - Selby Avenue Bridge, Spanning Short Line Railways track at Selby Avenue between Hamline & Snelling Avenues, Saint Paul, Ramsey County, MN

  19. Induction of fatal inflammation in LDL receptor and ApoA-I double-knockout mice fed dietary fat and cholesterol.

    PubMed

    Zabalawi, Manal; Bhat, Shaila; Loughlin, Tara; Thomas, Michael J; Alexander, Eric; Cline, Mark; Bullock, Bill; Willingham, Mark; Sorci-Thomas, Mary G

    2003-09-01

    Atherogenic response to dietary fat and cholesterol challenge was evaluated in mice lacking both the LDL receptor (LDLr(-/-)) and apoA-I (apoA-I(-/-)) gene, LDLr(-/-)/apoA-I(-/-) or double-knockout mice. Gender- and age-matched LDLr(-/-)/apoA-I(-/-) mice were fed a diet consisting of 0.1% cholesterol and 10% palm oil for 16 weeks and compared to LDLr(-/-) mice or single-knockout mice. The LDLr(-/-) mice showed a 6- to 7-fold increase in total plasma cholesterol (TPC) compared to their chow-fed mice counterparts, while LDLr(-/-)/apoA-I(-/-) mice showed only a 2- to 3-fold increase in TPC compared to their chow-fed controls. This differential response to the atherogenic diet was unanticipated, since chow-fed LDLr(-/-) and LDLr(-/-)/apoA-I(-/-) mice began the study with similar LDL levels and differed primarily in their HDL concentration. The 6-fold diet-induced increase in TPC observed in the LDLr(-/-) mice occurred mainly in VLDL/LDL and not in HDL. Mid-study plasma samples taken after 8 weeks of diet feeding showed that LDLr(-/-) mice had TPC concentrations approximately 60% of their 16-week level, while the LDLr(-/-)/apoA-I(-/-) mice had reached 100% of their 16-week TPC concentration after only 8 weeks of diet. Male LDLr(-/-) mice showed similar aortic cholesterol levels to male LDLr(-/-)/apoA-I(-/-) mice despite a 4-fold higher VLDL/LDL concentration in the LDLr(-/-) mice. A direct comparison of the severity of aortic atherosclerosis between female LDLr(-/-) and LDLr(-/-)/apoA-I(-/-) mice was compromised due to the loss of female LDLr(-/-)/apoA-I(-/-) mice between 10 and 14 weeks into the study. Diet-fed female and, with time, male LDLr(-/-)/apoA-I(-/-) mice suffered from severe ulcerated cutaneous xanthomatosis. This condition, combined with a complete depletion of adrenal cholesterol, manifested in fatal wasting of the affected mice. In conclusion, LDLr(-/-) and LDLr(-/-)/apoA-I(-/-) mice showed dramatic TPC differences in response to dietary fat and

  20. 28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS LINCOLN BOULEVARD, BIG LOST RIVER, AND NAVAL REACTORS FACILITY. F.C. TORKELSON DRAWING NUMBER 842-ARVFS-101-2. DATED OCTOBER 12, 1965. INEL INDEX CODE NUMBER: 075 0101 851 151969. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  1. Apolipoprotein A-I interactions with insulin secretion and production.

    PubMed

    Rye, Kerry-Anne; Barter, Philip J; Cochran, Blake J

    2016-02-01

    Human population studies have established that an elevated plasma high-density lipoprotein cholesterol (HDL-C) level is associated with a decreased risk of developing cardiovascular disease. In addition to having several potentially cardioprotective functions, HDLs and apolipoprotein (apo)A-I, the main HDL apolipoprotein, also have antidiabetic properties. Interventions that elevate plasma HDL-C and apoA-I levels improve glycemic control in people with type 2 diabetes mellitus by enhancing pancreatic β-cell function and increasing insulin sensitivity. This review is concerned with recent advances in understanding the mechanisms by which HDLs and apoA-I improve pancreatic β-cell function. HDLs and apoA-I increase insulin synthesis and secretion in pancreatic β cells. The underlying mechanism of this effect is similar to what has been reported for intestinally derived incretins, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, which both increase β-cell insulin secretion under high glucose conditions. This involves the activation of a heterotrimeric G protein Gαs subunit on the β-cell surface that leads to induction of a transmembrane adenylyl cyclase, increased intracellular cyclic adenosine monophosphate and Ca levels, and activation of protein kinase A. Protein kinase A increases insulin synthesis by excluding FoxO1 from the β-cell nucleus and derepressing transcription of the insulin gene.

  2. Butterfly extracts show antibacterial activity

    USDA-ARS?s Scientific Manuscript database

    Extracts of several British butterfly species were tested and shown to possess powerful bactericidal activity against the gram-positive bacteria Staphylococcus aureus (S. aureus). The active compounds were identified as hydroxylated pyrrolizidine alkaloids (PAs) related to loline with nitrogen at C-...

  3. Planning a Successful Tech Show

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2011-01-01

    Tech shows are a great way to introduce prospective students, parents, and local business and industry to a technology and engineering or career and technical education program. In addition to showcasing instructional programs, a tech show allows students to demonstrate their professionalism and skills, practice public presentations, and interact…

  4. Planning a Successful Tech Show

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2011-01-01

    Tech shows are a great way to introduce prospective students, parents, and local business and industry to a technology and engineering or career and technical education program. In addition to showcasing instructional programs, a tech show allows students to demonstrate their professionalism and skills, practice public presentations, and interact…

  5. Hey Teacher, Your Personality's Showing!

    ERIC Educational Resources Information Center

    Paulsen, James R.

    1977-01-01

    A study of 30 fourth, fifth, and sixth grade teachers and 300 of their students showed that a teacher's age, sex, and years of experience did not relate to students' mathematics achievement, but that more effective teachers showed greater "freedom from defensive behavior" than did less effective teachers. (DT)

  6. Satellite Movie Shows Erika Dissipate

    NASA Image and Video Library

    This animation of visible and infrared imagery from NOAA's GOES-West satellite from Aug. 27 to 29 shows Tropical Storm Erika move through the Eastern Caribbean Sea and dissipate near eastern Cuba. ...

  7. Satellite Animation Shows California Storms

    NASA Image and Video Library

    This animation of visible and infrared imagery from NOAA's GOES-West satellite shows a series of moisture-laden storms affecting California from Jan. 6 through Jan. 9, 2017. TRT: 00:36 Credit: NASA...

  8. Serum amyloid A protein forms a complex with a fragment of apolipoprotein A-I in the domestic blue fox: a protective mechanism against AA amyloidosis?

    PubMed

    Elisen, Ellen Johanne; Bruun, Cathrine Foyn; Nordstoga, Knut; Husby, Gunnar; Sletten, Knut

    2004-09-01

    The spontaneous occurrence of protein AA-type of amyloidosis varies among animal species. As reactive AA-type of amyloidosis has never been detected in the blue fox, we obtained acute phase sera to search for amyloid-protective elements. The purified SAA fraction was characterized by mass and sequence analyses to disclose any unique domains in the amino acid sequence. The data revealed an SAA protein with heterogeneities in several positions, and showed the typical insertion between positions 69 and 70. By comparing the amino acid sequence with that from other mammals, no unique sequence could be observed. However, a C-terminal fragment of apolipoprotein A-I (ApoA-I) was found attached to the SAA. The amino acid sequence of the ApoA-I fragment revealed a partially blocked and ragged N-terminus. A comparison of the amino acid sequence of ApoA-I with that from the dog showed that the ApoA-I fragment started about position 190, had an intact C-terminus, and showed an identical sequence in all positions, except one. Based on the data, we suggest an interaction of the C-terminal fragment of ApoA-I with the SAA protein that inhibits the AA fibrillogenesis in the blue fox.

  9. National Orange Show Photovoltaic Demonstration

    SciTech Connect

    Dan Jimenez Sheri Raborn, CPA; Tom Baker

    2008-03-31

    National Orange Show Photovoltaic Demonstration created a 400KW Photovoltaic self-generation plant at the National Orange Show Events Center (NOS). The NOS owns a 120-acre state fairground where it operates an events center and produces an annual citrus fair known as the Orange Show. The NOS governing board wanted to employ cost-saving programs for annual energy expenses. It is hoped the Photovoltaic program will result in overall savings for the NOS, help reduce the State's energy demands as relating to electrical power consumption, improve quality of life within the affected grid area as well as increase the energy efficiency of buildings at our venue. In addition, the potential to reduce operational expenses would have a tremendous effect on the ability of the NOS to service its community.

  10. Graphene Oxides Show Angiogenic Properties.

    PubMed

    Mukherjee, Sudip; Sriram, Pavithra; Barui, Ayan Kumar; Nethi, Susheel Kumar; Veeriah, Vimal; Chatterjee, Suvro; Suresh, Kattimuttathu Ittara; Patra, Chitta Ranjan

    2015-08-05

    Angiogenesis, a process resulting in the formation of new capillaries from the pre-existing vasculature plays vital role for the development of therapeutic approaches for cancer, atherosclerosis, wound healing, and cardiovascular diseases. In this report, the synthesis, characterization, and angiogenic properties of graphene oxide (GO) and reduced graphene oxide (rGO) have been demonstrated, observed through several in vitro and in vivo angiogenesis assays. The results here demonstrate that the intracellular formation of reactive oxygen species and reactive nitrogen species as well as activation of phospho-eNOS and phospho-Akt might be the plausible mechanisms for GO and rGO induced angiogenesis. The results altogether suggest the possibilities for the development of alternative angiogenic therapeutic approach for the treatment of cardiovascular related diseases where angiogenesis plays a significant role.

  11. Create a Polarized Light Show.

    ERIC Educational Resources Information Center

    Conrad, William H.

    1992-01-01

    Presents a lesson that introduces students to polarized light using a problem-solving approach. After illustrating the concept using a slinky and poster board with a vertical slot, students solve the problem of creating a polarized light show using Polya's problem-solving methods. (MDH)

  12. Creating Slide Show Book Reports.

    ERIC Educational Resources Information Center

    Taylor, Harriet G.; Stuhlmann, Janice M.

    1995-01-01

    Describes the use of "Kid Pix 2" software by fourth grade students to develop slide-show book reports. Highlights include collaboration with education majors from Louisiana State University, changes in attitudes of the education major students and elementary students, and problems with navigation and disk space. (LRW)

  13. Planetarium Show on Dark Matter

    SciTech Connect

    Barnett, R. Michael

    2016-05-31

    We describe a new planetarium show about Dark Matter entitled “Phantom of the Universe”. When completed in late 2014, it will feature the exciting story of dark matter, from the Big Bang to its anticipated discovery at the Large Hadron Collider.

  14. Aerial shows Stennis test stands

    NASA Image and Video Library

    2004-04-16

    An aerial photo shows the B-1/B-2 Test Stand (foreground), A-2 Test Stand (middle) and A-1 Test Stand (back). The historic stands have been used to test engines used on every manned Apollo and space shuttle mission.

  15. Phyllodes tumor showing intraductal growth.

    PubMed

    Makidono, Akari; Tsunoda, Hiroko; Mori, Miki; Yagata, Hiroshi; Onoda, Yui; Kikuchi, Mari; Nozaki, Taiki; Saida, Yukihisa; Nakamura, Seigo; Suzuki, Koyu

    2013-07-01

    Phyllodes tumor of the breast is a rare fibroepithelial lesion and particularly uncommon in adolescent girls. It is thought to arise from the periductal rather than intralobular stroma. Usually, it is seen as a well-defined mass. Phyllodes tumor showing intraductal growth is extremely rare. Here we report a girl who has a phyllodes tumor with intraductal growth.

  16. What Do Blood Tests Show?

    MedlinePlus

    ... A femtoliter is a measure of volume. Blood Glucose This table shows the ranges for blood glucose levels after 8 to 12 hours of fasting ( ... are a sign of prediabetes or diabetes. Plasma Glucose Results (mg/dL)* Diagnosis 70 to 99 Normal ...

  17. Magic Carpet Shows Its Colors

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The upper left image in this display is from the panoramic camera on the Mars Exploration Rover Spirit, showing the 'Magic Carpet' region near the rover at Gusev Crater, Mars, on Sol 7, the seventh martian day of its journey (Jan. 10, 2004). The lower image, also from the panoramic camera, is a monochrome (single filter) image of a rock in the 'Magic Carpet' area. Note that colored portions of the rock correlate with extracted spectra shown in the plot to the side. Four different types of materials are shown: the rock itself, the soil in front of the rock, some brighter soil on top of the rock, and some dust that has collected in small recesses on the rock face ('spots'). Each color on the spectra matches a line on the graph, showing how the panoramic camera's different colored filters are used to broadly assess the varying mineral compositions of martian rocks and soils.

  18. Magic Carpet Shows Its Colors

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The upper left image in this display is from the panoramic camera on the Mars Exploration Rover Spirit, showing the 'Magic Carpet' region near the rover at Gusev Crater, Mars, on Sol 7, the seventh martian day of its journey (Jan. 10, 2004). The lower image, also from the panoramic camera, is a monochrome (single filter) image of a rock in the 'Magic Carpet' area. Note that colored portions of the rock correlate with extracted spectra shown in the plot to the side. Four different types of materials are shown: the rock itself, the soil in front of the rock, some brighter soil on top of the rock, and some dust that has collected in small recesses on the rock face ('spots'). Each color on the spectra matches a line on the graph, showing how the panoramic camera's different colored filters are used to broadly assess the varying mineral compositions of martian rocks and soils.

  19. PPARγ Represses Apolipoprotein A-I Gene but Impedes TNFα-Mediated ApoA-I Downregulation in HepG2 Cells.

    PubMed

    Shavva, Vladimir S; Mogilenko, Denis A; Bogomolova, Alexandra M; Nikitin, Artemy A; Dizhe, Ella B; Efremov, Alexander M; Oleinikova, Galina N; Perevozchikov, Andrej P; Orlov, Sergey V

    2016-09-01

    Apolipoprotein A-I (ApoA-I) is the main anti-atherogenic component of human high-density lipoproteins (HDL). ApoA-I gene expression is regulated by several nuclear receptors, which are the sensors for metabolic changes during development of cardiovascular diseases. Activation of nuclear receptor PPARγ has been shown to impact lipid metabolism as well as inflammation. Here, we have shown that synthetic PPARγ agonist GW1929 decreases both ApoA-I mRNA and protein levels in HepG2 cells and the effect of GW1929 on apoA-I gene transcription depends on PPARγ. PPARγ binds to the sites A and C within the hepatic enhancer of apoA-I gene and the negative regulation of apoA-I gene transcription by PPARγ appears to be realized via the site C (-134 to -119). Ligand activation of PPARγ leads to an increase of LXRβ and a decrease of PPARα binding to the apoA-I gene hepatic enhancer in HepG2 cells. GW1929 abolishes the TNFα-mediated decrease of ApoA-I mRNA expression in both HepG2 and Caco-2 cells but does not block TNFα-mediated inhibition of ApoA-I protein secretion by HepG2 cells. These data demonstrate that complex of PPARγ with GW1929 is a negative regulator involved in the control of ApoA-I expression and secretion in human hepatocyte- and enterocyte-like cells. J. Cell. Biochem. 117: 2010-2022, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Interaction of Human Apolipoprotein A-I with Model Membranes Exhibiting Lipid Domains

    PubMed Central

    Arnulphi, Cristina; Sánchez, Susana A.; Tricerri, M. Alejandra; Gratton, Enrico; Jonas, Ana

    2005-01-01

    Several mechanisms for cell cholesterol efflux have been proposed, including membrane microsolubilization, suggesting that the existence of specific domains could enhance the transfer of lipids to apolipoproteins. In this work isothermal titration calorimetry, circular dichroism spectroscopy, and two-photon microscopy are used to study the interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) of 1-palmitoyl, 2-oleoyl phosphatidylcholine (POPC) and sphingomyelin (SM), with and without cholesterol. Below 30°C the calorimetric results show that apoA-I interaction with POPC/SM SUVs produces an exothermic reaction, characterized as nonclassical hydrophobic binding. The heat capacity change (ΔCp°) is small and positive, whereas it was larger and negative for pure POPC bilayers, in the absence of SM. Inclusion of cholesterol in the membranes induces changes in the observed thermodynamic pattern of binding and counteracts the formation of α-helices in the protein. Above 30°C the reactions are endothermic. Giant unilamellar vesicles (GUVs) of identical composition to the SUVs, and two-photon fluorescence microscopy techniques, were utilized to further characterize the interaction. Fluorescence imaging of the GUVs indicates coexistence of lipid domains under 30°C. Binding experiments and Laurdan generalized-polarization measurements suggest that there is no preferential binding of the labeled apoA-I to any particular domain. Changes in the content of α-helix, binding, and fluidity data are discussed in the framework of the thermodynamic parameters. PMID:15849246

  1. "Medicine show." Alice in Doctorland.

    PubMed

    1987-01-01

    This is an excerpt from the script of a 1939 play provided to the Institute of Social Medicine and Community Health by the Library of Congress Federal Theater Project Collection at George Mason University Library, Fairfax, Virginia, pages 2-1-8 thru 2-1-14. The Federal Theatre Project (FTP) was part of the New Deal program for the arts 1935-1939. Funded by the Works Progress Administration (WPA) its goal was to employ theater professionals from the relief rolls. A number of FTP plays deal with aspects of medicine and public health. Pageants, puppet shows and documentary plays celebrated progress in medical science while examining social controversies in medical services and the public health movement. "Medicine Show" sharply contrasts technological wonders with social backwardness. The play was rehearsed by the FTP but never opened because funding ended. A revised version ran on Broadway in 1940. The preceding comments are adapted from an excellent, well-illustrated review of five of these plays by Barabara Melosh: "The New Deal's Federal Theatre Project," Medical Heritage, Vol. 2, No. 1 (Jan/Feb 1986), pp. 36-47.

  2. Management of severe preeclampsia.

    PubMed

    Brichant, G; Dewandre, P Y; Foidart, J M; Brichant, J F

    2010-01-01

    Features of severe preeclampsia include severe proteinuric hypertension and symptoms of central nervous system dysfunction, hepatocellular injury, thrombocytopenia, oliguria, pulmonary oedema, cerebrovascular accident and severe intrauterine growth restriction. Women with severe preeclampsia must be hospitalized to confirm the diagnosis, to assess the severity of the disease, to monitor the progression of the disease and to try to stabilize the disease. Severe preeclampsia may be managed expectantly, in selected cases. The objective of expectant management in these patients is to improve neonatal outcome. Expectant management is based on antihypertensive treatment and prevention of end organ dysfunction. Antihypertensive treatment improves maternal outcome but has the potential to be deleterious for the foetus. Plasma volume expansion has been suggested for severe preeclampsia but trials failed to show any benefit. Magnesium sulfate is the anticonvulsivant of choice to treat or prevent eclampsia when indicated. Antenatal corticosteroids are recommended in severely preeclamptic women with 26-34 weeks gestation. Timing of delivery is based upon gestational age, severity of preeclampsia, maternal and foetal risks.

  3. Phoenix Scoop Inverted Showing Rasp

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This image taken by the Surface Stereo Imager on Sol 49, or the 49th Martian day of the mission (July 14, 2008), shows the silver colored rasp protruding from NASA's Phoenix Mars Lander's Robotic Arm scoop. The scoop is inverted and the rasp is pointing up.

    Shown with its forks pointing toward the ground is the thermal and electrical conductivity probe, at the lower right. The Robotic Arm Camera is pointed toward the ground.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is led by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  4. ShowMe3D

    SciTech Connect

    Sinclair, Michael B

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from the displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.

  5. [Severe rhabdomyolysis secondary to severe hypernatraemic dehydration].

    PubMed

    Mastro-Martínez, Ignacio; Montes-Arjona, Ana María; Escudero-Lirio, Margarita; Hernández-García, Bárbara; Fernández-Cantalejo Padial, José

    2015-01-01

    Rhabdomyolysis is a rare paediatric condition. The case is presented of a patient in whom this developed secondary to severe hypernatraemic dehydration following acute diarrhoea. Infant 11 months of age who presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents reported adequate preparation of artificial formula and oral rehydration solution. He was admitted with malaise, severe dehydration signs and symptoms, cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181 mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual clinical and renal function improvement. On the third day, slight axial hypotonia and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were observed, interpreted as rhabdomyolysis. He was treated with intravenous rehydration up to 1.5 times the basal requirements, and he showed a good clinical and biochemical response, being discharged 12 days after admission without motor sequelae. Severe hypernatraemia is described as a rare cause of rhabdomyolysis and renal failure. In critically ill patients, it is important to have a high index of suspicion for rhabdomyolysis and performing serial determinations of creatine phosphokinase for early detection and treatment. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Kepler Systems That Show Multiple Transiting Objects

    NASA Astrophysics Data System (ADS)

    Steffen, Jason H.; Fabrycky, D. C.; Ford, E. B.; Holman, M. J.; Lissauer, J. J.; Ragozzine, D.; Welsh, W. F.; Kepler Science Team

    2011-01-01

    Exoplanetary systems that have multiple transiting planets provide unique and important insight into the formation, evolution, and dynamics of exoplanetary systems. Kepler has announced the discovery of a confirmed planetary system with multiple transiting planets (Kepler 9, Holman et al. 2010) as well as several candidate planetary systems that show multiple transiting objects (Steffen et al. 2010). Kepler 9 shows deviations from a constant period due to the ongoing dynamical interactions between the confirmed planets. From these transit timing variations (TTV) one can measure the planetary masses from the photometric data alone. The presence of several systems with multiple transiting candidates from the first quarter of data indicate that Kepler should continue to find systems with multiple transiting planets. Such systems will provide important, general information about the histories of planetary systems.

  7. Mimas Showing False Colors #1

    NASA Technical Reports Server (NTRS)

    2005-01-01

    False color images of Saturn's moon, Mimas, reveal variation in either the composition or texture across its surface.

    During its approach to Mimas on Aug. 2, 2005, the Cassini spacecraft narrow-angle camera obtained multi-spectral views of the moon from a range of 228,000 kilometers (142,500 miles).

    The image at the left is a narrow angle clear-filter image, which was separately processed to enhance the contrast in brightness and sharpness of visible features. The image at the right is a color composite of narrow-angle ultraviolet, green, infrared and clear filter images, which have been specially processed to accentuate subtle changes in the spectral properties of Mimas' surface materials. To create this view, three color images (ultraviolet, green and infrared) were combined into a single black and white picture that isolates and maps regional color differences. This 'color map' was then superimposed over the clear-filter image at the left.

    The combination of color map and brightness image shows how the color differences across the Mimas surface materials are tied to geological features. Shades of blue and violet in the image at the right are used to identify surface materials that are bluer in color and have a weaker infrared brightness than average Mimas materials, which are represented by green.

    Herschel crater, a 140-kilometer-wide (88-mile) impact feature with a prominent central peak, is visible in the upper right of each image. The unusual bluer materials are seen to broadly surround Herschel crater. However, the bluer material is not uniformly distributed in and around the crater. Instead, it appears to be concentrated on the outside of the crater and more to the west than to the north or south. The origin of the color differences is not yet understood. It may represent ejecta material that was excavated from inside Mimas when the Herschel impact occurred. The bluer color of these materials may be caused by subtle differences in

  8. An urea, arginine and carnosine based cream (Ureadin Rx Db ISDIN) shows greater efficacy in the treatment of severe xerosis of the feet in Type 2 diabetic patients in comparison with glycerol-based emollient cream. A randomized, assessor-blinded, controlled trial

    PubMed Central

    2012-01-01

    Background Xerosis is a common skin disorder frequently observed in diabetic patients. An effective hydration of foot skin in diabetics is a relevant preventive strategy in order to maintain a healthy foot. Urea is considered an effective hydrating and emollient topical product. The aim of the present study was to evaluate the efficacy of topical urea 5% with arginine and carnosine (Ureadin Rx Db, ISDIN Spain) (UC) in comparison with glycerol-based emollient topical product (Dexeryl, Pierre Fabre) (EC), in Type 2 diabetic patients. Methods We assessed the effect of UC on skin hydration in a randomized, evaluator-blinded comparative study in 40 type II diabetic patients, aged 40–75 years, treated with UC or the comparator for 28 days with a twice-daily application. The principal outcomes were the Dryness Area Severity Index (DASI) Score and the Visual Analogue Score (VAS) for skin dryness evaluated at baseline and at the end of study period by an investigator unaware of treatment allocation. Results UC induced significantly greater hydration than EC with an 89% reduction in DASI score (from 1.6 to 0.2; p < 0.001) in comparison with baseline values. After 4 weeks, compared with the control group, DASI score in UC treated group was significantly lower (0.2 vs. 1.0; p = 0.048). VAS score (high values mean better hydration) significantly increased in both groups during treatment. VAS score at the end of treatment period was significantly higher in UC group in comparison with EC group (9.8 vs. 8.2; p = 0.05). Conclusion Application of urea 5%, arginine and carnosine cream increases skin hydration and alleviates the condition of skin dryness in Type 2 diabetic patients in comparison with a control glycerol-based emollient product. (Dutch Trials Register trial number 3328). PMID:23009311

  9. Francisella tularensis subsp. tularensis Group A.I, United States

    PubMed Central

    Birdsell, Dawn N.; Johansson, Anders; Öhrman, Caroline; Kaufman, Emily; Molins, Claudia; Pearson, Talima; Gyuranecz, Miklós; Naumann, Amber; Vogler, Amy J.; Myrtennäs, Kerstin; Larsson, Pär; Forsman, Mats; Sjödin, Andreas; Gillece, John D.; Schupp, James; Petersen, Jeannine M.; Keim, Paul

    2014-01-01

    We used whole-genome analysis and subsequent characterization of geographically diverse strains using new genetic signatures to identify distinct subgroups within Francisella tularensis subsp. tularensis group A.I: A.I.3, A.I.8, and A.I.12. These subgroups exhibit complex phylogeographic patterns within North America. The widest distribution was observed for A.I.12, which suggests an adaptive advantage. PMID:24755401

  10. Severe Combined Immunodeficiency Disorders.

    PubMed

    Chinn, Ivan K; Shearer, William T

    2015-11-01

    Severe combined immunodeficiency disorders represent pediatric emergencies due to absence of adaptive immune responses to infections. The conditions result from either intrinsic defects in T-cell development (ie, severe combined immunodeficiency disease [SCID]) or congenital athymia (eg, complete DiGeorge anomaly). Hematopoietic stem cell transplant provides the only clinically approved cure for SCID, although gene therapy research trials are showing significant promise. For greatest survival, patients should undergo transplant before 3.5 months of age and before the onset of infections. Newborn screening programs have yielded successful early identification and treatment of infants with SCID and congenital athymia in the United States.

  11. Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Ravani, Pietro; Obici, Laura; Dallera, Nadia; Del Barba, Andrea; Negrinelli, Alessandro; Tardanico, Regina; Nardi, Matilde; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2015-06-01

    Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.

  12. Conventional citrus of some scion/rootstock combinations show field tolerance under severe huanglongbing disease pressure

    USDA-ARS?s Scientific Manuscript database

    Although there are no commercial citrus varieties with strong huanglongbing (HLB) resistance, some field tolerance has been observed. The objective of this study was to assess cultivar field tolerance to HLB compared to sweet orange and grapefruit. To expedite the trial, nursery trees were purchased...

  13. Smokers Beware: Study Shows Increased Cadmium Levels in the Brain May Cause Severe Neurological Disorders

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Tobacco is one crop that accumulates cadmium, making smokers susceptible to higher levels of the metal in their bodies. The findings suggest that even a low-level exposure to a heavy metal like cadmium is likely to cause a change in the functions of neurons in the brain and the behavioral response to drugs of abuse.

  14. Smokers Beware: Study Shows Increased Cadmium Levels in the Brain May Cause Severe Neurological Disorders

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Tobacco is one crop that accumulates cadmium, making smokers susceptible to higher levels of the metal in their bodies. The findings suggest that even a low-level exposure to a heavy metal like cadmium is likely to cause a change in the functions of neurons in the brain and the behavioral response to drugs of abuse.

  15. Several recombinant capsid proteins of equine rhinitis a virus show potential as diagnostic antigens.

    PubMed

    Li, Fan; Stevenson, Rachel A; Crabb, Brendan S; Studdert, Michael J; Hartley, Carol A

    2005-06-01

    Equine rhinitis A virus (ERAV) is a significant pathogen of horses and is also closely related to Foot-and-mouth disease virus (FMDV). Despite these facts, knowledge of the prevalence and importance of ERAV infections remains limited, largely due to the absence of a simple, robust diagnostic assay. In this study, we compared the antigenicities of recombinant full-length and fragmented ERAV capsid proteins expressed in Escherichia coli by using sera from experimentally infected and naturally exposed horses. We found that, from the range of antigens tested, recombinant proteins encompassing the C-terminal region of VP1, full-length VP2, and the N-terminal region of VP2 reacted specifically with antibodies present in sera from each of the five experimentally infected horses examined. Antibodies to epitopes on VP2 (both native and recombinant forms) persisted longer postinfection (>105 days) than antibodies specific for epitopes on other fragments. Our data also suggest that B-cell epitopes within the C terminus of VP1 and N terminus of VP2 contribute to a large proportion of the total reactivity of recombinant VP1 and VP2, respectively. Importantly, the reactivity of these VP1 and VP2 recombinant proteins in enzyme-linked immunosorbent assays (ELISAs) correlated well with the results from a range of native antigen-based serological assays using sera from 12 field horses. This study provides promising candidates for development of a diagnostic ERAV ELISA.

  16. Isolation of novel Bacillus species showing high mosquitocidal activity against several mosquito species.

    PubMed

    Hayes, Sabrina R; Hudon, Michael; Park, Hyun-Woo

    2011-05-01

    Two novel mosquitocidal bacteria, VB17 and VB24, identified as new Bacillus species were isolated from dead mosquito larvae obtained in Florida aquatic habitats. Gas chromatographic analysis of fatty acid methyl esters (GC-FAME) and 16S rRNA sequencing indicated that VB24 is closely related to Bacillus sphaericus whereas VB17 does not have a close relationship with either Bacillus thuringiensis or B. sphaericus. Both isolates were significantly more active than B. sphaericus 2362 against Aedes taeniorhynchus, Anopheles quadrimaculatus, Culex quinquefasciatus larvae, and as active as B. sphaericus 2362 against Anopheles gambiae. Interestingly, however, both were not active against Aedes aegypti larvae, indicating some level of insecticidal specificity. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Recent trends in prostate cancer mortality show a continuous decrease in several countries.

    PubMed

    Bouchardy, Christine; Fioretta, Gerald; Rapiti, Elisabetta; Verkooijen, Helena Maria; Rapin, Charles Henry; Schmidlin, France; Miralbell, Raymond; Zanetti, Roberto

    2008-07-15

    Prostate specific antigen (PSA) screening was introduced to detect prostate cancer at an early stage and to reduce prostate cancer-specific mortality. Until results from clinical trials are available, the efficacy of PSA screening in reducing prostate cancer mortality can be estimated by surveillance of prostate cancer mortality trends. Our study analyzes recent trends in prostate cancer mortality in 38 countries. We used the IARC-WHO cancer mortality database and performed joinpoint analysis to examine prostate cancer mortality trends and identified 3 patterns. In USA, and to a lesser extent in Germany, Switzerland, Canada, France, Italy and Spain, prostate cancer-specific mortality decreased to a level lower than before the introduction of PSA screening. In Australia, New Zealand, Austria, Finland, The Netherlands, Norway, United Kingdom, Hungary, Slovakia, Israel, Singapore, Sweden and Portugal, mortality from prostate cancer decreased but rates remain higher than before the introduction of PSA screening. Prostate cancer mortality continued to increase in Belgium, Denmark, Greece, Ireland, Bulgaria, Czech Republic, Belarus, Ukraine, Russian Federation, Romania, Poland, Argentina, Chile, Cuba, Mexico, Japan, China Hong Kong and the Republic of Korea. The trends in prostate cancer mortality rates in examined countries suggest that PSA screening may be effective in reducing mortality from prostate cancer. (c) 2008 Wiley-Liss, Inc.

  18. Predicting Severe Duststorms

    NASA Technical Reports Server (NTRS)

    Woicheshyn, P. M.

    1985-01-01

    Combined human/machine forecasting technique shows promise. Severe duststorms in Great Plains forecast with fair reliability. Forecasts derived from combination of human expertise and variety of meteorological information sources, including all current and recent weather observations, standard National Meteorological Center (NMC) computer analyses for surface and upper air, and NMC 12-, 24-, 36-, and 48-hour prognostication charts generated by Limited Fine Mesh computer model.

  19. Plasma lipid transport in the hedgehog: partial characterization of structure and function of apolipoprotein A-I.

    PubMed

    Sparrow, D A; Laplaud, P M; Saboureau, M; Zhou, G; Dolphin, P J; Gotto, A M; Sparrow, J T

    1995-03-01

    Apart from exhibiting the presence of lipoprotein [a] in its plasma, another interest of the European hedgehog in lipoprotein research lies in the quantitative prominence of a complex spectrum of high density lipoproteins (HDL) and very high density lipoproteins (VHDL) as cholesterol transporters in plasma (Laplaud, P. M. et al. 1989. Biochim. Biophys. Acta. 1005: 143-156). We, therefore, initiated studies in the field of reverse cholesterol transport in the hedgehog. As a first step, we characterized apolipoprotein A-I (apoA-I), the main protein component of hedgehog HDL and VHDL. Proteolytic cleavage of apoA-I (M(r) approx. 27 kDa) using two different enzymes resulted in two sets of peptides that were subsequently purified by high performance liquid chromatography, and that allowed us determination of the complete protein sequence. Hedgehog apoA-I thus consists of 241 amino acid residues and exhibits an overall 58% homology to its human counterpart, i.e., the lowest value observed to date among mammalian species. However, it retained the general organization common to all known apoA-Is, i.e., a series of amphipathic helical segments punctuated by proline residues. Circular dichroism experiments indicated a helical content of approx. 45%, increasing to approx. 58% in the presence of lecithin unilamellar liposomes. Apart from other differences, amino acid composition analysis shows that hedgehog apoA-I contains four isoleucine residues, while this amino acid is totally absent from the corresponding protein in higher mammals. Polyclonal antibodies raised against hedgehog apoA-I failed to detect any cross-reactivity between the animal and human proteins, although comparative prediction of the respective antigenic structures using the Hopp-Woods algorithm indicated that several potentially antigenic sites may occur in similar regions of the protein. Finally, hedgehog apoA-I was shown to be able to activate lecithin:cholesterol acyl transferase, although it was 4 to 5

  20. Apolipoproteins A-I, A-II and E in cholestatic liver disease.

    PubMed

    Florén, C H; Gustafson, A

    1985-04-01

    Apolipoproteins A-I, A-II and E were determined in the plasma of nine patients (five females, four males) with cholestatic liver disease (eight patients with primary biliary cirrhosis and one patient with sclerosing cholangitis). Plasma concentrations were measured by electroimmunoassay in the fasting state, postprandially after ingestion of either 100 g fat as whipping cream or a light mixed meal with or without addition of wheat fibre. Concentrations of apolipoproteins A-I and A-II were low in patients with cholestatic liver disease and A-I levels correlated inversely with the severity of liver disease as measured by bilirubin levels (r = -0.66). No changes in plasma apolipoprotein A-I, A-II or E concentrations occurred postprandially. There was an inverse correlation between plasma concentrations of apolipoproteins A-I and E (p less than 0.05, r = -0.68). A close relation existed between the ratio of apolipoprotein E to apolipoprotein A-I and plasma bile salt concentration (r = 0.80, p less than 0.01) and serum bilirubin (r = 0.76, p less than 0.01). This implies that in cholestatic liver disease apolipoprotein E and A-I levels reflect the degree of cholestasis.

  1. Regulation of the promoter of rat apolipoprotein A-I gene in cultured cells

    SciTech Connect

    Chao, Y.; Pan, T.; Wu, T.; Hao, Q.; Yamin, T.; Kroon, P.A.

    1987-05-01

    In order to study the regulation of the promoter of apolipoprotein (apo) A-I gene, they joined the 5' end of rat apo A-I gene (1.9 Kb) to the coding region of bacterial chloramphenicol acetyltransferase (CAT) gene. The chimeric gene produced high levels of CAT activity in both mouse L cells and Hep G2 cells in transient expression assays. Ethanol increased the levels of rat apo A-I promoter activity in both cells. However, dexamethasone increased rat apo A-I promoter activity only in Hep G2 cells. Similar results were obtained in stable expression cell lines. Nucleotide deletion experiments showed DNA sequences between -149 and -469 base pairs upstream from the rat apo A-I transcription site are required for the high level of expression and that the regulatory sequences are located further upstream. These data demonstrated that the 5' end of rat apo A-I gene contains sequences which are responsible for the regulation of apo A-I expression by ethanol and dexamethasone and that the expression and regulation of rat apo A-I promoter are cell specific.

  2. Lower HDL-C and apolipoprotein A-I are related to higher glomerular filtration rate in subjects without kidney disease[S

    PubMed Central

    Krikken, Jan A.; Gansevoort, Ron T.; Dullaart, Robin P. F.

    2010-01-01

    Animal experiments show that the kidney contributes to apolipoprotein (apo)A-I catabolism. We tested relationships of HDL cholesterol (HDL-C) and apo-I with kidney function in subjects without severe chronic kidney disease. Included was a random sample of the general population (part of the PREVEND cohort). Kidney function [estimated glomerular filtration rate (e-GFR) by two well-established equations and creatinine clearance], HDL-C, triglycerides, apoA-I and insulin resistance (HOMAir) were measured in 2,484 fasting subjects (e-GFR≥45 ml/min/1.73m2) without macroalbuminuria, cardiovascular disease, diabetes, or the use of anti-hypertensives and/or lipid-lowering agents. HDL-C (r = −0.056 to −0.102, P < 0.01 to < 0.001) and apo A-I (r = −0.096 to −0.126, P < 0.001) were correlated inversely with both GFR estimates and creatinine clearance in univariate analyses. Multiple linear regression analyses also demonstrated inverse relationships of HDL-C and apoA-I with all measures of kidney function even after adjustment for age, sex, waist circumference, HOMAir, triglycerides, and urinary albumin excretion (P = 0.053 to 0.004). In conclusion, HDL-C and apoA-I are inversely related to e-GFR and creatinine clearance in subjects without severely compromised kidney function, which fits the concept that the kidney contributes to apoA-I regulation in humans. High glomerular filtration rate may be an independent determinant of a pro-atherogenic lipoprotein profile. PMID:20211930

  3. Upgrade Summer Severe Weather Tool

    NASA Technical Reports Server (NTRS)

    Watson, Leela

    2011-01-01

    The goal of this task was to upgrade to the existing severe weather database by adding observations from the 2010 warm season, update the verification dataset with results from the 2010 warm season, use statistical logistic regression analysis on the database and develop a new forecast tool. The AMU analyzed 7 stability parameters that showed the possibility of providing guidance in forecasting severe weather, calculated verification statistics for the Total Threat Score (TTS), and calculated warm season verification statistics for the 2010 season. The AMU also performed statistical logistic regression analysis on the 22-year severe weather database. The results indicated that the logistic regression equation did not show an increase in skill over the previously developed TTS. The equation showed less accuracy than TTS at predicting severe weather, little ability to distinguish between severe and non-severe weather days, and worse standard categorical accuracy measures and skill scores over TTS.

  4. Correlations Between Serum Apolipoprotein A-I and Formation of Vocal Cord Polyp.

    PubMed

    Zhang, Hui-Ping; Zhang, Rong

    2017-05-01

    This study aims to investigate the correlations between serum apolipoprotein A-I (ApoA-I) and the formation of vocal cord polyps (VCPs). This study used the nonmatched case-control study method. The serum total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, ApoA-I, apolipoprotein B (ApoB), and ApoA-I/ApoB levels of 89 VCP patients and 87 normal volunteers were compared. Additionally, such VCP-related factors as excessive vocal use, vocal abuse, smoking, drinking, and the size of VCPs were analyzed. The two groups did not significantly differ with regard to triglyceride, low-density lipoprotein cholesterol, ApoB, and ApoA-I/ApoB levels (P > 0.05), whereas they did significantly differ with regard to TC, HDL-C, and ApoA-I levels (P < 0.05) according to independent t tests. Logistic regression analysis showed that excessive vocal use and vocal abuse were risk factors for VCPs (P < 0.05), with odds ratio values of 5.675 and 12.781, respectively. The ApoA-I level was negatively associated with VCPs (P < 0.05), with an odds ratio of 0.511; however, TC and HDL-C were not associated with the formation of VCPs (P > 0.05). The size of VCPs in females was negatively correlated with the serum ApoA-I level (r = -0.349, P = 0.032), whereas that in males was not (P > 0.05). As the serum ApoA-I level was negatively correlated with the formation of VCPs, ApoA-I may reduce the risk of VCPs. These findings may facilitate the prevention and treatment of VCPs. Copyright © 2017. Published by Elsevier Inc.

  5. Anti-apolipoprotein A-I antibodies and paraoxonase 1 activity in Systemic Lupus Erythematosus

    PubMed Central

    Ahmed, Mohammed Mahmoud; Elserougy, Eman Mahmoud; Al-Gazzar, Iman Ibrahim; Fikry, Iman Mohamed; Habib, Dawoud Fakhry; Younes, Khaled Mohamed; Salem, Neveen Abd El-hameed

    2013-01-01

    Systemic lupus erythematosus (SLE) patients have an increased risk of atherosclerosis. Identification of at-risk patients and the pathogenesis of atherosclerosis in SLE remain elusive. Paraoxonase 1 (PON1) and anti-apolipoprotein A-I antibody (anti-Apo A-I) appear to have a potential role in premature atherosclerosis in SLE. The aim of this work was to study PON1 activity and anti-Apo A-I antibody in SLE female patients and to demonstrate their relations to disease activity as well as disease related damage. Forty SLE female patients and 40 apparently healthy volunteers were included. Anti-Apo A-I antibodies levels and PON1 activity levels were assessed. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and systemic Lupus International Collaboration Clinics (SLICC)/American College of Rheumatology (ACR) damage index were preformed in all patients. Compared with controls, SLE patients showed significantly lower PON1 activity and significantly higher titers of anti-Apo A-I. Anti-Apo A-I antibody titers correlated inversely with PON1 activity. Elevated titers of anti-Apo A-I antibody and reduced PON activity were related to increased SLEDAI and (SLICC/ACR) damage index scores. We concluded that there is decreased PON1 activity and formation of anti-Apo A-I antibodies in female patients with SLE. SLE-disease activity assessed by SLEDAI and SLE disease related organ damage assessed by SLICC/ACR damage index are negatively correlated with PON1 activity and positively correlated with anti-Apo A-I antibodies. PON1 activity and anti-Apo A-I antibodies might be involved in the pathogenesis of atherosclerosis in SLE patients. PMID:26622215

  6. Age and injury severity.

    PubMed

    Brorsson, B

    1989-01-01

    This study aims at showing if and to what extent injury severity in frontal car crashes increases with the age of front seat occupants. Data on 2658 belted drivers and front seat passengers in Volvo private car series 140, 240 and 740/760, involved in frontal crashes were extracted from the Volvo Car Crash Register. The results show that the risk of injury resulting in "medical observation" does not increase systematically with age. However, the risk of fracture with any localization is more than three times higher among those aged 65-74 than in those aged 18-24, and the risk of fracture in the rib cage is nearly eleven times higher among the older than in the younger age group. It can be concluded that the incidence of specific types of injuries - as exemplified with fractures of any localization and fractures in the rib cage - increases with advancing age.

  7. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier Disease.

    PubMed Central

    Francis, G A; Knopp, R H; Oram, J F

    1995-01-01

    Tangier disease is a rare genetic disorder characterized by extremely low plasma levels of HDL and apo A-I, deposition of cholesteryl esters in tissues, and a high prevalence of cardiovascular disease. We examined the possibility that HDL apolipoprotein-mediated removal of cellular lipids may be defective in Tangier disease. With fibroblasts from normal subjects, purified apo A-I cleared cells of cholesteryl esters, depleted cellular free cholesterol pools available for esterification, and stimulated efflux of radiolabeled cholesterol, phosphatidylcholine, and sphingomyelin. With fibroblasts from two unrelated Tangier patients, however, apo A-I had little or no effect on any of these lipid transport processes. Intact HDL also was unable to clear cholesteryl esters from Tangier cells even though it promoted radiolabeled cholesterol efflux to levels 50-70% normal. Passive desorption of radiolabeled cholesterol or phospholipids into medium containing albumin or trypsinized HDL was normal for Tangier cells. Binding studies showed that the interaction of apo A-I with high-affinity binding sites on Tangier fibroblasts was abnormal. These results indicate that apo A-I has an impaired ability to remove cholesterol and phospholipid from Tangier fibroblasts, possibly because of a defective interaction of apo A-I with cell-surface binding sites. Failure of apo A-I to acquire cellular lipids may account for the rapid catabolism of nascent HDL particles and the low plasma HDL levels in Tangier disease. Images PMID:7615839

  8. Helical structure and stability in human apolipoprotein A-I by hydrogen exchange and mass spectrometry

    PubMed Central

    Chetty, Palaniappan Sevugan; Mayne, Leland; Lund-Katz, Sissel; Stranz, David; Englander, S. Walter; Phillips, Michael C.

    2009-01-01

    Apolipoprotein A-I (apoA-I) stabilizes anti-atherogenic high density lipoprotein particles (HDL) in the circulation and governs their biogenesis, metabolism, and functional interactions. To decipher these important structure–function relationships, it will be necessary to understand the structure, stability, and plasticity of the apoA-I molecule. Biophysical studies show that lipid-free apoA-I contains a large amount of α-helical structure but the location of this structure and its properties are not established. We used hydrogen-deuterium exchange coupled with a fragmentation-separation method and mass spectrometric analysis to study human lipid-free apoA-I in its physiologically pertinent monomeric form. The acquisition of ≈100 overlapping peptide fragments that redundantly cover the 243-residue apoA-I polypeptide made it possible to define the positions and stabilities of helical segments and to draw inferences about their interactions and dynamic properties. Residues 7–44, 54–65, 70–78, 81–115, and 147–178 form α-helices, accounting for a helical content of 48 ± 3%, in agreement with circular dichroism measurements (49%). At 3 to 5 kcal/mol in free energy of stabilization, the helices are far more stable than could be achieved in isolation, indicating mutually stabilizing helix bundle interactions. However the helical structure is dynamic, unfolding and refolding in seconds, allowing facile apoA-I reorganization during HDL particle formation and remodeling. PMID:19850866

  9. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice.

    PubMed Central

    Berthou, L; Duverger, N; Emmanuel, F; Langouët, S; Auwerx, J; Guillouzo, A; Fruchart, J C; Rubin, E; Denèfle, P; Staels, B; Branellec, D

    1996-01-01

    The regulation of liver apolipoprotein (apo) A-I gene expression by fibrates was studied in human apo A-I transgenic mice containing a human genomic DNA fragment driving apo A-I expression in liver. Treatment with fenofibrate (0.5% wt/wt) for 7 d increased plasma human apo A-I levels up to 750% and HDL-cholesterol levels up to 200% with a shift to larger particles. The increase in human apo A-I plasma levels was time and dose dependent and was already evident after 3 d at the highest dose (0.5% wt/wt) of fenofibrate. In contrast, plasma mouse apo A-I concentration was decreased after fenofibrate in nontransgenic mice. The increase in plasma human apo A-I levels after fenofibrate treatment was associated with a 97% increase in hepatic human apo A-I mRNA, whereas mouse apo A-I mRNA levels decreased to 51%. In nontransgenic mice, a similar down-regulation of hepatic apo A-I mRNA levels was observed. Nuclear run-on experiments demonstrated that the increase in human apo A-I and the decrease in mouse apo A-I gene expression after fenofibrate occurred at the transcriptional level. Since part of the effects of fibrates are mediated through the nuclear receptor PPAR (peroxisome proliferator-activated receptor), the expression of the acyl CoA oxidase (ACO) gene was measured as a control of PPAR activation. Both in transgenic and nontransgenic mice, fenofibrate induced ACO mRNA levels up to sixfold. When transgenic mice were treated with gemfibrozil (0.5% wt/wt) plasma human apo A-I and HDL-cholesterol levels increased 32 and 73%, respectively, above control levels. The weaker effect of this compound on human apo A-I and HDL-cholesterol levels correlated with a less pronounced impact on ACO mRNA levels (a threefold increase) suggesting that the level of induction of human apo A-I gene is related to the PPAR activating potency of the fibrate used. Treatment of human primary hepatocytes with fenofibric acid (500 microM) provoked an 83 and 50% increase in apo A-I secretion and

  10. Apolipoprotein A-I Modulates Atherosclerosis Through Lymphatic Vessel-Dependent Mechanisms in Mice.

    PubMed

    Milasan, Andreea; Jean, Gabriel; Dallaire, François; Tardif, Jean-Claude; Merhi, Yahye; Sorci-Thomas, Mary; Martel, Catherine

    2017-09-22

    Subcutaneously injected lipid-free apoA-I (apolipoprotein A-I) reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without increasing high-density lipoprotein-cholesterol concentrations. Lymphatic vessels are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and particular attention has been brought to the role of the collecting lymphatic vessels in early atherosclerosis-related lymphatic dysfunction. In the present study, we address whether and how preservation of collecting lymphatic function contributes to the protective effect of apoA-I. Atherosclerotic Ldlr(-/-) mice treated with low-dose lipid-free apoA-I showed enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr(-/-) mice when compared with albumin-control mice. Treatment of human lymphatic endothelial cells with apoA-I increased the adhesion of human platelets on lymphatic endothelial cells, in a bridge-like manner, a mechanism that could strengthen endothelial cell-cell junctions and limit atherosclerosis-associated collecting lymphatic vessel dysfunction. Experiments performed with blood platelets isolated from apoA-I-treated Ldlr(-/-) mice revealed that apoA-I decreased ex vivo platelet aggregation. This suggests that in vivo apoA-I treatment limits platelet thrombotic potential in blood while maintaining the platelet activity needed to sustain adequate lymphatic function. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  11. 12 CFR Appendixes A-I to Part 171 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false A Appendixes A-I to Part 171 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Appendixes A-I to Part 171 ...

  12. 12 CFR Appendixes A-I to Part 171 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false A Appendixes A-I to Part 171 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Appendixes A-I to Part 171 ...

  13. 12 CFR Appendixes A-I to Part 171 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false A Appendixes A-I to Part 171 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Appendixes A-I to Part 171 ...

  14. Star Shows It Has The Right Stuff

    NASA Astrophysics Data System (ADS)

    2004-01-01

    Astronomers have used an observation by NASA's Chandra X-ray Observatory to make the best case yet that a star can be engulfed by its companion star and survive. This discovery will help astronomers better understand how closely coupled stars, and perhaps even stars and planets, evolve when one of the stars expands enormously in its red giant phase. The binary star system known as V471 Tauri comprises a white dwarf star (the primary) in a close orbit -- one thirtieth of the distance between Mercury and the Sun -- with a normal Sun-like star (the secondary). Chandra's data showed that the hot upper atmosphere of the secondary star has a deficit of carbon atoms relative to nitrogen atoms. "This deficit of carbon atoms is the first clear observational evidence that the normal star was engulfed by its companion in the past," according to Jeremy Drake of the Smithsonian Astrophysical Observatory in Cambridge, MA, who coauthored an article on V471 in The Astrophysical Journal Letters with Marek Sarna of the N. Copernicus Astronomical Center in Poland. The white dwarf star was once a star several times as massive as the Sun. Nuclear fusion reactions in the core of such a star convert carbon into nitrogen over a period of about a billion years. When the fuel in the core of the star is exhausted, the core collapses, triggering more energetic nuclear reactions that cause the star to expand and transform into a red giant before eventually collapsing to become a white dwarf. The carbon-poor material in the core of the red giant is mixed with outer part of the star, so its atmosphere shows a deficit of carbon, as compared with Sun-like stars. The X-ray spectra of a red giant star (top panel) and a Sun-like star (bottom panel) show the large difference in the peaks due to carbon atoms in the two stars. Theoretical calculations indicate that a red giant in a binary system can completely envelop its companion star and dramatically affect its evolution. During this common envelope

  15. Current concepts of severe asthma.

    PubMed

    Ray, Anuradha; Raundhal, Mahesh; Oriss, Timothy B; Ray, Prabir; Wenzel, Sally E

    2016-07-01

    The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development.

  16. Conformation and Lipid Binding of a C-Terminal (198-243) Peptide of Human Apolipoprotein A-I (apoA-I)†

    PubMed Central

    Zhu, Hongli L.; Atkinson, David

    2008-01-01

    Human apolipoprotein A-I (apoA-I) is the principle apolipoprotein of high-density lipoproteins that are critically involved in reverse cholesterol transport. The intrinsically flexibility of apoA-I has hindered studies of the structural and functional details of the protein. Our strategy is to study peptide models representing different regions of apoA-I. Our previous report on [1-44]apoA-I demonstrated that this N-terminal region is unstructured and folds into ~ 60% α-helix with a moderate lipid binding affinity. We now present details of the conformation and lipid interaction of a C-terminal 46 residue peptide, [198-243]apoA-I, encompassing putative helix repeats 10, 9 and the second half of repeat 8 from the C-terminus of apoA-I. Far ultraviolet circular dichroism spectra show that [198-243] apoA-I is also unfolded in aqueous solution. However, self-association induces ~ 50% α-helix in the peptide. The self-associated peptide exists mainly as a tetramer, as determined by native electrophoresis, cross-linking with glutaraldehyde and unfolding data from circular dichroism (CD) and differential scanning calorimetry (DSC). In the presence of a number of lipid mimicking detergents, above their CMC, ~ 60% α-helix was induced in the peptide. In contrast, SDS, an anionic lipid mimicking detergent, induced helical folding in the peptide at a concentration of ~ 0.003% (~ 100 μM), ~ 70 fold below its typical CMC (0.17–0.23% or 6–8 mM). Both monomeric and tetrameric peptide can solublize dimyristoyl phosphatidyl choline (DMPC) liposomes and fold into ~ 60% α-helix. Fractionation by density gradient ultracentrifugation and visualization by negative staining electromicroscopy, demonstrated that the peptide binds to DMPC with high affinity to form at least two sizes of relatively homogenous discoidal HDL-like particles depending on the initial lipid:peptide ratio. The characteristics (lipid:peptide w/w, diameter and density) of both complexes are similar to those of

  17. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia.

    PubMed Central

    Ng, D S; Leiter, L A; Vezina, C; Connelly, P W; Hegele, R A

    1994-01-01

    We report a Canadian kindred with a novel mutation in the apolipoprotein (apo) A-I gene causing analphalipoproteinemia. The 34-yr-old proband, product of a consanguineous marriage, had bilateral retinopathy, bilateral cataracts, spinocerebellar ataxia, and tendon xanthomata. High density lipoprotein cholesterol (HDL-C) was < 0.1 mM and apoA-I was undetectable. Genomic DNA sequencing of the proband's apoA-I gene identified a nonsense mutation at codon [-2], which we designate as Q[-2]X. This mutation causes a loss of endonuclease digestion sites for both BbvI and Fnu4HI. Genotyping identified four additional homozygotes, four heterozygotes, and two unaffected subjects among the first-degree relatives. Q[-2]X homozygosity causes a selective failure to produce any portion of mature apoA-I, resulting in very low plasma level of HDL. Heterozygosity results in approximately half-normal apoA-I and HDL. Gradient gel electrophoresis and differential electroimmunodiffusion assay revealed that the HDL particles of the homozygotes had peak Stokes diameter of 7.9 nm and contained apoA-II without apoA-I (Lp-AII). Heterozygotes had an additional fraction of HDL3-like particles. Two of the proband's affected sisters had documented premature coronary heart disease. This kindred, the third reported apoA-I gene mutation causing isolated complete apoA-I deficiency, appears to be at significantly increased risk for atherosclerosis. Images PMID:8282791

  18. RVX 208: A novel BET protein inhibitor, role as an inducer of apo A-I/HDL and beyond.

    PubMed

    Ghosh, Gopal C; Bhadra, Rajarshi; Ghosh, Raktim K; Banerjee, Kinjal; Gupta, Anjan

    2017-08-01

    Low-density cholesterol (LDL) has been the prime target of currently available lipid-lowering therapies although current research is expanding the focus beyond LDL lowering and has included high-density cholesterol (HDL) also as the target. Bromo and extra-terminal (BET) proteins are implicated in the regulation of transcription of several regulatory genes and regulation of proinflammatory pathways. As atherosclerosis is an inflammatory pathway and studies showed that BET inhibition has a role in inhibiting inflammation, the concept of BET inhibition came in the field of atherosclerosis. RVX 208 is a novel, orally active, BET protein inhibitor and the only BET inhibitor currently available in the field of atherosclerosis. RVX 208 acts primarily by increasing apo A-I (apolipoprotein A-I) and HDL levels. RVX 208 has a novel action of increasing larger, more cardio-protective HDL particles. Post hoc analysis of Phase II trials also showed that RVX 208 reduced major adverse cardiovascular events (MACE) in treated patients, over and above that of apo A-I/HDL increasing action. This MACE reducing actions of RVX 208 were largely due to its novel anti-inflammatory actions. Currently, a phase III trial, BETonMACE, is recruiting patients to look for the effects of RVX 208 in patients with increased risk of atherosclerotic cardiovascular disease. So BET inhibitors act in multiple ways to inhibit and modulate atherosclerosis and would be an emerging and potential option in the management of multifactorial disease like coronary artery disease by inhibiting a single substrate. But we need long-term phase III trial data's to look for effects on real-world patients. © 2017 John Wiley & Sons Ltd.

  19. Thermal Stability of Apolipoprotein A-I in High-Density Lipoproteins by Molecular Dynamics

    PubMed Central

    Jones, Martin K.; Catte, Andrea; Patterson, James C.; Gu, Feifei; Chen, Jianguo; Li, Ling; Segrest, Jere P.

    2009-01-01

    Abstract Apolipoprotein (apo) A-I is an unusually flexible protein whose lipid-associated structure is poorly understood. Thermal denaturation, which is used to measure the global helix stability of high-density lipoprotein (HDL)-associated apoA-I, provides no information about local helix stability. Here we report the use of temperature jump molecular dynamics (MD) simulations to scan the per-residue helix stability of apoA-I in phospholipid-rich HDL. When three 20 ns MD simulations were performed at 500 K on each of two particles created by MD simulations at 310 K, bilayers remained intact but expanded by 40%, and total apoA-I helicity decreased from 95% to 72%. Of significance, the conformations of the overlapping N- and C-terminal domains of apoA-I in the particles were unusually mobile, exposing hydrocarbon regions of the phospholipid to solvent; a lack of buried interhelical salt bridges in the terminal domains correlated with increased mobility. Nondenaturing gradient gels show that 40% expansion of the phospholipid surface of 100:2 particles by addition of palmitoyloleoylphosphatidylcholine exceeds the threshold of particle stability. As a unifying hypothesis, we propose that the terminal domains of apoA-I are phospholipid concentration-sensitive molecular triggers for fusion/remodeling of HDL particles. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling has substantial biomedical implications. PMID:19167289

  20. Human Apolipoprotein A-I-Derived Amyloid: Its Association with Atherosclerosis

    PubMed Central

    Ramella, Nahuel A.; Rimoldi, Omar J.; Prieto, Eduardo D.; Schinella, Guillermo R.; Sanchez, Susana A.; Jaureguiberry, María S.; Vela, María E.

    2011-01-01

    Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis. PMID:21811627

  1. Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Obici, Laura; Tardanico, Regina; Röcken, Christoph; Viola, Battista Fabio; Capistrano, Mariano; Donadei, Simona; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2005-12-01

    Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.

  2. A mass spectrometric determination of the conformation of dimeric apolipoprotein A-I in discoidal high density lipoproteins.

    PubMed

    Silva, R A Gangani D; Hilliard, George M; Li, Ling; Segrest, Jere P; Davidson, W Sean

    2005-06-21

    Discoidal forms of high density lipoproteins (HDL) are critical intermediates between lipid-poor apolipoprotein A-I (apo A-I), the major protein constituent of HDL, and the mature spherical forms that comprise the bulk of circulating particles. Thus, many studies have focused on understanding apoA-I structure in discs reconstituted in vitro. Recent theoretical and experimental work supports a "belt" model for apoA-I in which repeating amphipathic helical domains run parallel to the plane of the lipid disc. However, disc-associated apoA-I can adopt several tertiary arrangements that are consistent with a belt orientation. To distinguish among these, we cross-linked near-neighbor Lys groups in homogeneous 96 A discs containing exactly two molecules of apoA-I. After delipidation and tryptic digestion, mass spectrometry was used to identify 9 intermolecular and 11 intramolecular cross-links. The cross-linking pattern strongly suggests a "double-belt" molecular arrangement for apoA-I in which two apoA-I molecules wrap around the lipid bilayer disc forming two stacked rings in an antiparallel orientation with helix 5 of each apoA-I in juxtaposition (LL5/5 orientation). The data also suggests the presence of an additional double-belt orientation with a shifted helical registry (LL5/2 orientation). Furthermore, a 78 A particle with two molecules of apoA-I fit a similar double-belt motif with evidence for conformational changes in the N-terminus and the region near helix 5. A comparison of this work to a previous study is suggestive that a third molecule of apoA-I can form a hairpin in larger particles containing three molecules of apoA-I.

  3. Increased Binding of Apolipoproteins A-I and E4 to Triglyceride-Rich Lipoproteins is linked to Induction of Hypertriglyceridemia.

    PubMed

    Gorshkova, Irina N; Atkinson, David

    2017-01-01

    Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins. The studies show that the apoA-I and apoE4 forms that induce HTG have a destabilized and more loosely folded conformation in solution than their counterparts not associated with HTG. Disruption of the protein salt bridge networks by the mutations is likely responsible for the observed structural changes. Each apoA-I and apoE4 form that induced HTG show enhanced binding to model TG-rich particles. HTG appeared to positively correlate with the apolipoprotein ability to bind to TG-rich particles. This implies that in vivo, the conformational changes in the apolipoproteins that induce HTG facilitate their binding to plasma TG-rich lipoproteins. We discuss metabolic pathways leading to the development of HTG that may result from enhanced binding of the apolipoproteins to TG-rich lipoproteins in circulation. While various factors may be involved in the development of HTG in humans, it is possible that structural alterations that increase affinity of apolipoproteins to TG-rich lipoproteins may contribute to some cases of this disorder.

  4. VLA Shows "Boiling" in Atmosphere of Betelgeuse

    NASA Astrophysics Data System (ADS)

    1998-04-01

    A team of astronomers says that observations with the National Science Foundation's Very Large Array (VLA) radio telescope show that a neighboring bloated star has giant convective plumes propelling gas from its surface (photosphere) up into the star's atmosphere. This new information contradicts long-held ideas that such stellar atmospheres are more uniform, and may resolve questions about how the star's atmosphere attains its enormous size as well as how dust and gas is driven away from the star. Jeremy Lim of the Academia Sinica Institute of Astronomy & Astrophysics in Taiwan; Chris Carilli, Anthony Beasley, and Ralph Marson of the National Radio Astronomy Observatory (NRAO) in Socorro, NM; and Stephen White of the University of Maryland studied the red-supergiant star Betelgeuse, about 430 light-years away in the constellation Orion. They reported their findings in the April 9 issue of the scientific journal Nature. "These radio-telescope images confirm that Betelgeuse -- already more than 600 times larger than our Sun -- has a dense atmosphere that extends to many times larger still than the star itself," said Lim. "The highest-resolution image shows the star's atmosphere to have a remarkably complex structure." "To our surprise," added White, "the images also show that most of the gas in the atmosphere is only about as hot as that on the surface. Previously, all of it was thought to be very much hotter." The astronomers used the VLA to make images of Betelgeuse at a variety of radio frequencies. The series of radio observations measured the temperature of the star's atmosphere at different heights. Previous observations with the Hubble Space Telescope (HST) at ultraviolet wavelengths showed that the star's atmosphere contains very hot gas at about twice the surface temperature. The VLA images showed that there also is lower-temperature gas throughout the atmosphere. This gas is near the surface temperature at low heights and decreases in temperature

  5. Dengue and Severe Dengue

    MedlinePlus

    ... serotypes increase the risk of developing severe dengue. Global burden of dengue The incidence of dengue has ... accumulation, respiratory distress, severe bleeding, or organ impairment. Warning signs occur 3–7 days after the first ...

  6. Severe Asthma in Children.

    PubMed

    Chipps, Bradley E; Parikh, Neil G; Maharaj, Sheena K

    2017-04-01

    The aim of this study is to characterize, diagnose, evaluate, and treat severe childhood asthma. Understanding the occurrence of the physiologic and clinical presentations of childhood severe asthma, the treatment and response may be predicted by biomarkers, but the patient's response is highly variable. The onset of severe asthma occurs early and is primarily predicted by severity of viral infection and coexistence of the atopic state.

  7. The A's Have It: Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma.

    PubMed

    Yao, Xianglan; Gordon, Elizabeth M; Barochia, Amisha V; Remaley, Alan T; Levine, Stewart J

    2016-08-01

    New treatments are needed for patients with asthma who are refractory to standard therapies, such as individuals with a phenotype of "type 2-low" inflammation. This important clinical problem could potentially be addressed by the development of apolipoprotein A-I (apoA-I) mimetic peptides. ApoA-I interacts with its cellular receptor, the ATP-binding cassette subfamily A, member 1 (ABCA1), to facilitate cholesterol efflux out of cells to form nascent high-density lipoprotein particles. The ability of the apoA-I/ABCA1 pathway to promote cholesterol efflux from cells that mediate adaptive immunity, such as antigen-presenting cells, can attenuate their function. Data from experimental murine models have shown that the apoA-I/ABCA1 pathway can reduce neutrophilic airway inflammation, primarily by suppressing the production of granulocyte-colony stimulating factor. Furthermore, administration of apoA-I mimetic peptides to experimental murine models of allergic asthma has decreased both neutrophilic and eosinophilic airway inflammation, as well as airway hyperresponsiveness and mucous cell metaplasia. Higher serum levels of apoA-I have also been associated with less severe airflow obstruction in patients with asthma. Collectively, these results suggest that the apoA-I/ABCA1 pathway may have a protective effect in asthma, and support the concept of advancing inhaled apoA-I mimetic peptides to clinical trials that can assess their safety and effectiveness. Thus, we propose that the development of inhaled apoA-I mimetic peptides as a new treatment could represent a clinical advance for patients with severe asthma who are unresponsive to other therapies. Published by Elsevier Inc.

  8. High-Density Lipoprotein Biogenesis: Defining the Domains Involved in Human Apolipoprotein A-I Lipidation.

    PubMed

    Pollard, Ricquita D; Fulp, Brian; Sorci-Thomas, Mary G; Thomas, Michael J

    2016-09-06

    The first step in removing cholesterol from a cell is the ATP-binding cassette transporter 1 (ABCA1)-driven transfer of cholesterol to lipid-free or lipid-poor apolipoprotein A-I (apoA-I), which yields cholesterol-rich nascent high-density lipoprotein (nHDL) that then matures in plasma to spherical, cholesteryl ester-rich HDL. However, lipid-free apoA-I has a three-dimensional (3D) conformation that is significantly different from that of lipidated apoA-I on nHDL. By comparing the lipid-free apoA-I 3D conformation of apoA-I to that of 9-14 nm diameter nHDL, we formulated the hypothetical helical domain transitions that might drive particle formation. To test the hypothesis, ten apoA-I mutants were prepared that contained two strategically placed cysteines several of which could form intramolecular disulfide bonds and others that could not form these bonds. Mass spectrometry was used to identify amino acid sequence and intramolecular disulfide bond formation. Recombinant HDL (rHDL) formation was assessed with this group of apoA-I mutants. ABCA1-driven nHDL formation was measured in four mutants and wild-type apoA-I. The mutants contained cysteine substitutions in one of three regions: the N-terminus, amino acids 34 and 55 (E34C to S55C), central domain amino acids 104 and 162 (F104C to H162C), and the C-terminus, amino acids 200 and 233 (L200C to L233C). Mutants were studied in the locked form, with an intramolecular disulfide bond present, or unlocked form, with the cysteine thiol blocked by alkylation. Only small amounts of rHDL or nHDL were formed upon locking the central domain. We conclude that both the N- and C-terminal ends assist in the initial steps in lipid acquisition, but that opening of the central domain was essential for particle formation.

  9. Taking Your Show on the Road.

    ERIC Educational Resources Information Center

    Buchanan, Suzanne

    1998-01-01

    Describes a local interpretation program in New England that uses a motorcoach to take visitors on a day-long tour of several sites in the region. Explains how to create similar programs elsewhere and gives advice for preparing for the tour, orienting tour members, interpreting on the road, pacing tours over a day, and stopping at tour sites. (PVD)

  10. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity

    PubMed Central

    Mohan, Vijee; Gupta, Soni; Thomas, Sherinmol; Mickey, Hanjabam; Charakana, Chaitanya; Chauhan, Vineeta Singh; Sharma, Kapil; Kumar, Rakesh; Tyagi, Kamal; Sarma, Supriya; Gupta, Suresh Kumar; Kilambi, Himabindu Vasuki; Nongmaithem, Sapana; Kumari, Alka; Gupta, Prateek; Sreelakshmi, Yellamaraju; Sharma, Rameshwar

    2016-01-01

    Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS), carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1) involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima’D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future. PMID:27077652

  11. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.

    PubMed

    Mohan, Vijee; Gupta, Soni; Thomas, Sherinmol; Mickey, Hanjabam; Charakana, Chaitanya; Chauhan, Vineeta Singh; Sharma, Kapil; Kumar, Rakesh; Tyagi, Kamal; Sarma, Supriya; Gupta, Suresh Kumar; Kilambi, Himabindu Vasuki; Nongmaithem, Sapana; Kumari, Alka; Gupta, Prateek; Sreelakshmi, Yellamaraju; Sharma, Rameshwar

    2016-01-01

    Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS), carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1) involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.

  12. Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis.

    PubMed

    Gkouskou, K K; Ioannou, M; Pavlopoulos, G A; Georgila, K; Siganou, A; Nikolaidis, G; Kanellis, D C; Moore, S; Papadakis, K A; Kardassis, D; Iliopoulos, I; McDyer, F A; Drakos, E; Eliopoulos, A G

    2016-05-12

    In both humans with long-standing ulcerative colitis and mouse models of colitis-associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies.

  13. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    PubMed

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226.

  14. Serum apolipoproteins A-I and B in 2,854 children from a biracial community: Bogalusa Heart Study.

    PubMed

    Srinivasan, S R; Freedman, D S; Sharma, C; Webber, L S; Berenson, G S

    1986-08-01

    Serum apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) profiles were examined in 2,854 children, 5 to 17 years of age, from a total biracial community. Black boys had higher apo A-I levels than white boys (P less than .001), whereas girls showed no such race-related difference. Black-white difference in apo A-I persisted among boys with similar triglyceride levels provided that triglyceride levels were high. The ratio of high-density lipoprotein cholesterol (HDL-C)/apo A-I was higher in black than in white children, irrespective of sex (P less than .001). Only black children showed sex-related differences for apo A-I (boys greater than girls, P less than .05). Sex-related differences were seen in white children for HDL-C/apo A-I ratio (boys greater than girls, P less than .001) and in children of both races for apoB (girls greater than boys, P less than .01). Age-related changes were more apparent for apo A-I and HDL-C/apo A-I ratio than for apo B. A progressive decrease in apo A-I was noted during sexual maturation only in white boys. The magnitude of inverse association of apo B to HDL-C was less strong in black children (P less than .01). Although apo A-I was inversely correlated with very low-density lipoprotein cholesterol and triglycerides in white children, no association was noted in black children. These findings are indicative of intrinsic metabolic differences among the race-sex groups, resulting in variability in lipoprotein composition and levels and atherogenic potential.

  15. Serving Up Activities for TV Cooking Shows.

    ERIC Educational Resources Information Center

    Katchen, Johanna E.

    This paper documents a presentation given on the use of English-language television cooking shows in English-as-a-Second-Language (ESL) and English-as-a-Foreign-Language (EFL) classrooms in Taiwan. Such shows can be ideal for classroom use, since they have a predictable structure consisting of short segments, are of interest to most students,…

  16. The Language of Show Biz: A Dictionary.

    ERIC Educational Resources Information Center

    Sergel, Sherman Louis, Ed.

    This dictionary of the language of show biz provides the layman with definitions and essays on terms and expressions often used in show business. The overall pattern of selection was intended to be more rather than less inclusive, though radio, television, and film terms were deliberately omitted. Lengthy explanations are sometimes used to express…

  17. 47 CFR 90.505 - Showing required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MOBILE RADIO SERVICES Developmental Operation § 90.505 Showing required. (a) Except as provided in paragraph (b) of this section, each application for developmental operation shall be accompanied by a showing that: (1) The applicant has an organized plan of development leading to a specific objective;...

  18. The Physics of Equestrian Show Jumping

    ERIC Educational Resources Information Center

    Stinner, Art

    2014-01-01

    This article discusses the kinematics and dynamics of equestrian show jumping. For some time I have attended a series of show jumping events at Spruce Meadows, an international equestrian center near Calgary, Alberta, often referred to as the "Wimbledon of equestrian jumping." I have always had a desire to write an article such as this…

  19. The Physics of Equestrian Show Jumping

    ERIC Educational Resources Information Center

    Stinner, Art

    2014-01-01

    This article discusses the kinematics and dynamics of equestrian show jumping. For some time I have attended a series of show jumping events at Spruce Meadows, an international equestrian center near Calgary, Alberta, often referred to as the "Wimbledon of equestrian jumping." I have always had a desire to write an article such as this…

  20. The Language of Show Biz: A Dictionary.

    ERIC Educational Resources Information Center

    Sergel, Sherman Louis, Ed.

    This dictionary of the language of show biz provides the layman with definitions and essays on terms and expressions often used in show business. The overall pattern of selection was intended to be more rather than less inclusive, though radio, television, and film terms were deliberately omitted. Lengthy explanations are sometimes used to express…

  1. Decreased apolipoprotein A-I level indicates poor prognosis in extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Quan, Qi; Chen, Qi; Chen, Ping; Jiang, Li; Li, Tingwei; Qiu, Huijuan; Zhang, Bei

    2016-01-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an invasive lymphoid malignancy with unfavorable survival, for which a prognostic model has not yet been validated. We hypothesized that serum apolipoprotein A-I (ApoA-I) may serve as a novel prognostic marker for ENKTL. A total of 236 newly diagnosed cases of ENKTL were analyzed retrospectively. The optimal cutoff value for the serum ApoA-I level was determined to be 0.95 g/L. A total of 154 and 82 cases were assigned to the high and low ApoA-I groups, respectively. Patients in the low ApoA-I group tended to present with poorer clinical features, a lower complete remission rate (P=0.001), and poor median progression-free survival (P<0.001) and overall survival (P<0.001). Multivariate analysis using Cox model showed that the serum ApoA-I level was an independent prognostic marker of overall survival (P<0.001) and progression-free survival (P<0.001) for ENKTL patients. For cases in the low-risk group, as assessed by International Prognostic Index, Prognosis Index for peripheral T-cell lymphoma, unspecified, and Korean Prognostic Index, the serum ApoA-I level was able to differentiate cases with poor outcomes from cases with good outcomes. Our results showed that the baseline serum ApoA-I level was helpful for predicting ENKTL prognosis.

  2. Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.

    PubMed

    Miles, Rebecca R; Perry, William; Haas, Joseph V; Mosior, Marian K; N'Cho, Mathias; Wang, Jian W J; Yu, Peng; Calley, John; Yue, Yong; Carter, Quincy; Han, Bomie; Foxworthy, Patricia; Kowala, Mark C; Ryan, Timothy P; Solenberg, Patricia J; Michael, Laura F

    2013-03-01

    Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation. Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21,789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I. Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis. Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed. Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest. The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function. Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.

  3. Severe malarial anaemia.

    PubMed

    Casals-Pascual, C; Roberts, D J

    2006-03-01

    This review describes the importance of severe malarial anaemia as a public health problem, and the clinical and pathophysiological aspects of this syndrome. The review also highlights the recent advances in our understanding of the epidemiological, clinical, cellular and molecular aspects of severe malarial anaemia.

  4. TODDLERS WITH ELEVATED AUTISM SYMPTOMS SHOW SLOWED HABITUATION TO FACES

    PubMed Central

    Webb, Sara Jane; Jones, Emily J. H.; Merkle, Kristen; Namkung, Jessica; Toth, Karen; Greenson, Jessica; Murias, Michael; Dawson, Geraldine

    2010-01-01

    We explored social information processing and its relation to social and communicative symptoms in toddlers with Autism Spectrum Disorder (ASD) and their siblings. Toddlers with more severe symptoms of autism showed slower habituation to faces than comparison groups; slower face learning correlated with poorer social skills and lower verbal ability. Unaffected toddlers who were siblings of children with ASD also showed slower habituation to faces compared with toddlers without siblings with ASD. We conclude that slower rates of face learning may be an endophenotype of ASD and is associated with more severe symptoms among affected individuals. PMID:20301009

  5. Management of severe osteoporosis.

    PubMed

    Miller, Paul D

    2016-01-01

    Severe osteoporosis represents a disease of high mortality and morbidity. Recognition of what constitutes and causes severe osteoporosis and aggressive intervention with pharmacological agents with evidence to reduce fracture risk are outlined in this review. This review is a blend of evidence obtained from literature searches from PubMed and The National Library of Medicine (USA), clinical experience and the author's opinions. The review covers the recognition of what constitutes severe osteoporosis, and provides up-to-date references on this sub-set of high risk patients. Severe osteoporosis can be classified by using measurements of bone densitometry, identification of prevalent fractures, and, knowledge of what additional risk factors contribute to high fracture risk. Once recognized, the potential consequences of severe osteoporosis can be mitigated by appropriate selection of pharmacological therapies and modalities to reduce the risk for falling.

  6. A fast semi-quantitative LC-MS method for measurement of intact apolipoprotein A-I reveals novel proteoforms in serum.

    PubMed

    Gåfvels, M; Bengtson, P

    2015-03-10

    Surrogate markers for reverse cholesterol transport (RCT) efficiency such as HDL cholesterol and immune methods for apolipoprotein A-I (ApoA-I) may not fully reflect the actual efficiency of the RCT pathway. Several genetic variants and different posttranslational proteoforms of ApoA-I may unevenly affect the functionality of the HDL particle to efflux cholesterol. A method employing top-down immunoaffinity LC-MS of ApoA-I in order to characterize the most prevalent ApoA-I proteoforms in human plasma is described. Diluted plasma was directly injected into a 2D LC-MS system consisting of an affinity column and an analytical column. Enriched ApoA-I fractions were introduced into the MS and intact or fragmented ApoA-I was analyzed. ApoA-I as detected by the described LC-MS method distributes into at least 14 major potential proteoforms exceeding detection limit in human plasma. Substantial amounts of ApoA-I in plasma were found to occur as truncated, oxidized, glycated and glycosylated proteoforms. Levels of glycated ApoA-I distinguished significantly diabetic from non-diabetic samples. In addition novel truncated and glycosylated proteoforms were detected. ApoA-I proteoforms measured by LC-MS represent a useful approach to augment the clinical picture of ApoA-I and its function in health and disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Polyadenylation site prediction using PolyA-iEP method.

    PubMed

    Kavakiotis, Ioannis; Tzanis, George; Vlahavas, Ioannis

    2014-01-01

    This chapter presents a method called PolyA-iEP that has been developed for the prediction of polyadenylation sites. More precisely, PolyA-iEP is a method that recognizes mRNA 3'ends which contain polyadenylation sites. It is a modular system which consists of two main components. The first exploits the advantages of emerging patterns and the second is a distance-based scoring method. The outputs of the two components are finally combined by a classifier. The final results reach very high scores of sensitivity and specificity.

  8. GOES Satellite Data Shows Tornado Development

    NASA Image and Video Library

    This animation of NOAA's GOES-East satellite data shows the development and movement of the weather system that spawned tornadoes affecting the southern and eastern U.S. states on April 27-29, 2014...

  9. Career development at London Vet Show.

    PubMed

    2016-09-03

    Are you considering a career change? Perhaps you want help to develop within your current role? Either way, you will find a relevant session in the BVA Career Development stream at the London Vet Show in November. British Veterinary Association.

  10. Experimental Drug Shows Promise Against Dangerous Viruses

    MedlinePlus

    ... 166953.html Experimental Drug Shows Promise Against Dangerous Viruses Medicine worked in lab tests against germs that ... researchers say. Coronaviruses are a large family of viruses that infect birds and mammals, including humans. These ...

  11. Laser Therapy Shows Promise Against Eye 'Floaters'

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_167324.html Laser Therapy Shows Promise Against Eye 'Floaters' These spots ... 2017 THURSDAY, July 20, 2017 (HealthDay News) -- A laser treatment can reduce spots in people's vision known ...

  12. TRMM Satellite Shows Heavy Rainfall in Cristina

    NASA Image and Video Library

    NASA's TRMM satellite rainfall data was overlaid on an enhanced visible/infrared image from NOAA's GOES-East satellite showing cloud and rainfall extent. Green areas indicate rainfall at over 20 mm...

  13. Spacecraft Image Mashup Shows Galactic Collision

    NASA Image and Video Library

    This new composite image from the Chandra X-ray Observatory, the Hubble Space Telescope, and the Spitzer Space Telescope shows two colliding galaxies more than a 100 million years after they first ...

  14. Study Shows How Zika Attacks Infant Brain

    MedlinePlus

    ... gov/news/fullstory_162514.html Study Shows How Zika Attacks Infant Brain Virus can copy itself thousands ... New research paints a chilling portrait of how Zika ravages the infant brain. Scientists from the U.S. ...

  15. Do dogs (Canis familiaris) show contagious yawning?

    PubMed

    Harr, Aimee L; Gilbert, Valerie R; Phillips, Kimberley A

    2009-11-01

    We report an experimental investigation into whether domesticated dogs display contagious yawning. Fifteen dogs were shown video clips of (1) humans and (2) dogs displaying yawns and open-mouth expressions (not yawns) to investigate whether dogs showed contagious yawning to either of these social stimuli. Only one dog performed significantly more yawns during or shortly after viewing yawning videos than to the open-mouth videos, and most of these yawns occurred to the human videos. No dogs showed significantly more yawning to the open-mouth videos (human or dog). The percentage of dogs showing contagious yawning was less than chimpanzees and humans showing this behavior, and considerably less than a recently published report investigating this behavior in dogs (Joly-Mascheroni et al. in Biol Lett 4:446-448, 2008).

  16. Show me: automatic presentation for visual analysis.

    PubMed

    Mackinlay, Jock; Hanrahan, Pat; Stolte, Chris

    2007-01-01

    This paper describes Show Me, an integrated set of user interface commands and defaults that incorporate automatic presentation into a commercial visual analysis system called Tableau. A key aspect of Tableau is VizQL, a language for specifying views, which is used by Show Me to extend automatic presentation to the generation of tables of views (commonly called small multiple displays). A key research issue for the commercial application of automatic presentation is the user experience, which must support the flow of visual analysis. User experience has not been the focus of previous research on automatic presentation. The Show Me user experience includes the automatic selection of mark types, a command to add a single field to a view, and a pair of commands to build views for multiple fields. Although the use of these defaults and commands is optional, user interface logs indicate that Show Me is used by commercial users.

  17. Poverty Harder on Women's Hearts, Research Shows

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163168.html Poverty Harder on Women's Hearts, Research Shows Poor females ... reduce the burden of cardiovascular disease around the world," Peters said. The study findings were published online ...

  18. Gene Therapy Shows Promise for Aggressive Lymphoma

    MedlinePlus

    ... fullstory_163824.html Gene Therapy Shows Promise for Aggressive Lymphoma Over one-third of patients appeared disease- ... 2017 (HealthDay News) -- An experimental gene therapy for aggressive non-Hodgkin lymphoma beat back more than a ...

  19. Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase deficiency.

    PubMed

    Munoz, Tatiana; Patel, Jinesh; Badilla-Porras, Ramses; Kronick, Jonathan; Mercimek-Mahmutoglu, Saadet

    2015-01-01

    Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessively inherited inborn error of folate metabolism. We report a new patient with severe MTHFR deficiency who presented at age 4 months with early onset severe scoliosis associated with severe hypotonia. Markedly decreased MTHFR enzyme activity (0.3 nmoles CHO/mg protein/h; reference range>9) and compound heterozygous mutations (c. 1304T>C; p.Phe435Ser and c.1539dup; p.Glu514Argfs∗24) in the MTHFR gene confirmed the diagnosis. She was treated with vitamin B12, folic acid and betaine supplementation and showed improvements in her developmental milestones and hypotonia. To the best of our knowledge, this is the first patient with MTHFR deficiency reported with severe early onset scoliosis. Despite the late diagnosis and treatment initiation, she showed favorable short-term neurodevelopmental outcome. This case suggests that homocysteine measurement should be included in the investigations of patients with developmental delay, hypotonia and scoliosis within first year of life prior to organizing genetic investigations.

  20. Severe childhood malnutrition.

    PubMed

    Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J; Kerac, Marko; Trehan, Indi; Briend, André

    2017-09-21

    The main forms of childhood malnutrition occur predominantly in children <5 years of age living in low-income and middle-income countries and include stunting, wasting and kwashiorkor, of which severe wasting and kwashiorkor are commonly referred to as severe acute malnutrition. Here, we use the term 'severe malnutrition' to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide therapeutic end points. The early detection of severe wasting and kwashiorkor and outpatient therapy for these conditions using ready-to-use therapeutic foods form the cornerstone of modern therapy, and only a small percentage of children require inpatient care. However, the normalization of physiological and metabolic functions in children with malnutrition is challenging, and children remain at high risk of relapse and death. Further research is urgently needed to improve our understanding of the pathophysiology of severe malnutrition, especially the mechanisms causing kwashiorkor, and to develop new interventions for prevention and treatment.

  1. Severe asthma in children

    PubMed Central

    Guilbert, TW; Bacharier, LB; Fitzpatrick, AM

    2015-01-01

    Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of ICS or oral corticosteroids. Children with severe asthma may fall into two categories, difficult-to-treat asthma or severe therapy-resistant asthma. Difficult-to-treat asthma is defined as poor control due to an incorrect diagnosis or comorbidities, poor adherence due to adverse psychological or environmental factors. In contrast, treatment-resistant is defined as difficult asthma despite management of these factors. It is increasingly recognized that severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes that have been described in children with severe asthma. Guideline based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. The recommendation is that children with severe asthma be treated with higher-dose inhaled or oral corticosteroids combined with long-acting beta-agonists and other add on therapies such as antileukotrienes and methylxanthines. It is important to identify and address the influences that make asthma difficult to control including reviewing the diagnosis and the removal of causal or aggravating factors. Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future. PMID:25213041

  2. Severe asthma in children.

    PubMed

    Guilbert, Theresa W; Bacharier, Leonard B; Fitzpatrick, Anne M

    2014-01-01

    Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of inhaled corticosteroids or oral corticosteroids. Children with severe asthma may fall into 2 categories, difficult-to-treat asthma or severe therapy-resistant asthma. Difficult-to-treat asthma is defined as poor control due to an incorrect diagnosis or comorbidities, or poor adherence due to adverse psychological or environmental factors. In contrast, treatment resistant is defined as difficult asthma despite management of these factors. It is increasingly recognized that severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes that have been described in children with severe asthma. Guideline-based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. The recommendation is that children with severe asthma be treated with higher-dose inhaled or oral corticosteroids combined with long-acting β-agonists and other add-on therapies, such as antileukotrienes and methylxanthines. It is important to identify and address the influences that make asthma difficult to control, including reviewing the diagnosis and removing causal or aggravating factors. Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future.

  3. Parthenium Dermatitis Severity Score to Assess Clinical Severity of Disease

    PubMed Central

    Verma, Kaushal K; Bansal, Arika; Bhari, Neetu; Sethuraman, Gomathy

    2017-01-01

    Background: Parthenium dermatitis is the most common type of airborne contact dermatitis in India. It is a chronic disease of a remitting and relapsing course with significant morbidity and distress, but there is no scoring system to assess its severity. Aim: To design a scoring system for the assessment of clinical severity of disease in Parthenium dermatitis and to use this scoring system in various studies to determine its sensitivity, specificity, and reproducibility. Methods and Results: In our first few studies on Parthenium dermatitis, we designed and used a basic clinical severity scoring system based on itching, morphology of the lesions, and areas involved. However, in subsequent studies, we modified it to the present scoring system as Parthenium dermatitis severity score (PDSS). Our studies showed the high sensitivity of PDSS in characterization of the disease severity at the given point of time, as well as to determine the efficacy of a prescribed treatment modality which was reliable and reproducible. Conclusion: Thus, PDSS may be used by clinicians for appropriate scoring of the clinical severity of Parthenium dermatitis and in monitoring the disease response to therapy. PMID:28216730

  4. [Severe multifactorial hyponatremia].

    PubMed

    Manes, Massimo; Radin, Elisabetta; Pellù, Valentina; Caputo, Donatella; Gabrielli, Danila; Molino, Andrea; Paternoster, Giuseppe; Parodi, Emanuele; Nebiolo, Pier Eugenio

    2017-01-01

    Hyponatremia is the most common electrolyte disorder observed in hospitalized patients. The most severe forms are neurological and potentially fatal emergencies; yet increased morbidity, length of hospital stay and costs associated with less severe forms are aspects of major concern. Nephrologists are frequently consulted regarding the therapeutic management and the key pathophysiological issues of hyponatremia, as this latter aspect represents a true challenge in an emergency setting. We report a case of a woman admitted to the emergency room for gait instability caused by a very severe multifactorial hyponatremia with a favourable clinical outcome.

  5. Educational Outreach: The Space Science Road Show

    NASA Astrophysics Data System (ADS)

    Cox, N. L. J.

    2002-01-01

    The poster presented will give an overview of a study towards a "Space Road Show". The topic of this show is space science. The target group is adolescents, aged 12 to 15, at Dutch high schools. The show and its accompanying experiments would be supported with suitable educational material. Science teachers at schools can decide for themselves if they want to use this material in advance, afterwards or not at all. The aims of this outreach effort are: to motivate students for space science and engineering, to help them understand the importance of (space) research, to give them a positive feeling about the possibilities offered by space and in the process give them useful knowledge on space basics. The show revolves around three main themes: applications, science and society. First the students will get some historical background on the importance of space/astronomy to civilization. Secondly they will learn more about novel uses of space. On the one hand they will learn of "Views on Earth" involving technologies like Remote Sensing (or Spying), Communication, Broadcasting, GPS and Telemedicine. On the other hand they will experience "Views on Space" illustrated by past, present and future space research missions, like the space exploration missions (Cassini/Huygens, Mars Express and Rosetta) and the astronomy missions (Soho and XMM). Meanwhile, the students will learn more about the technology of launchers and satellites needed to accomplish these space missions. Throughout the show and especially towards the end attention will be paid to the third theme "Why go to space"? Other reasons for people to get into space will be explored. An important question in this is the commercial (manned) exploration of space. Thus, the questions of benefit of space to society are integrated in the entire show. It raises some fundamental questions about the effects of space travel on our environment, poverty and other moral issues. The show attempts to connect scientific with

  6. Try P.R.A.I.S.E.

    ERIC Educational Resources Information Center

    Wollam, Scott A.

    1979-01-01

    P.R.A.I.S.E. (Positive Reinforcement and Individualized Systematic Economics) is a multifaceted money system which utilizes positive and negative reinforcement and, at the same time, incorporates peer pressure and reinforcement for behavior modification. The system motivates, relates closely to life situations, and can be applied to all areas of…

  7. Severe Exoplanetary Storm

    NASA Image and Video Library

    2009-01-28

    These computer-generated images from NASA Spitzer Space Telescope chart the development of severe weather patterns on the highly eccentric exoplanet HD 80606b during the days after its closest approach to its parent star.

  8. Liquid Crystal Research Shows Deformation By Drying

    NASA Technical Reports Server (NTRS)

    2003-01-01

    These images, from David Weitz's liquid crystal research, show ordered uniform sized droplets (upper left) before they are dried from their solution. After the droplets are dried (upper right), they are viewed with crossed polarizers that show the deformation caused by drying, a process that orients the bipolar structure of the liquid crystal within the droplets. When an electric field is applied to the dried droplets (lower left), and then increased (lower right), the liquid crystal within the droplets switches its alignment, thereby reducing the amount of light that can be scattered by the droplets when a beam is shone through them.

  9. The association between the apolipoprotein B/A-I ratio and coronary calcification may differ depending on kidney function in a healthy population.

    PubMed

    Kim, Seok-Hyung; Oh, Donghwan; Jung, Kwon Soo; Lee, Jung Eun; Kim, Hyunwook; Kim, Hyung Jong; Kim, Beom Seok; Park, Hyeong Cheon; Lee, Byoung Kwon; Choi, Hoon Young

    2017-01-01

    The apolipoprotein B/A-1 ratio has been reported to be one of the strongest risk predictors of cardiovascular events. However, its prognostic value for cardiovascular disease is still uncertain, especially in patients with chronic kidney disease. This study aimed to investigate whether the association between the apolipoprotein B/A-I ratio and coronary artery calcification differed according to kidney function in a healthy population. Of the data from 7,780 participants from the medical records database in Gangnam Severance Hospital from 2005 through 2016, a cross-sectional analysis included participants with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 determined based on the Chronic Kidney Disease -Epidemiology Collaboration equation (n  =  1,800). Mild renal insufficiency was defined as an eGFR of 60-90 mL/min/1.73 m2. Coronary artery calcification measured with computed tomography was defined as an above-zero score. Logistic regression analyses were used to determine the association between coronary calcification and the apolipoprotein B/A-I ratio according to eGFR by adjusting for the influence of confounders. The mean apolipoprotein B/A-I level was significantly higher in the participants with coronary artery calcification than in the participants without coronary artery calcification. The apolipoprotein B/A-I ratio was significantly different according to coronary artery calcification in the participants with normal kidney function, but in the participants with mild renal insufficiency, it was not different. After adjusting for age, male sex, systolic blood pressure, body mass index, current smoking status, and fasting plasma glucose, the apolipoprotein B/A-I ratio was significantly associated with an increased risk of coronary artery calcification in participants with normal kidney function (odds ratio = 2.411, p = 0.011), while in the participants with mild renal insufficiency, the apolipoprotein B/A-I ratio was not associated

  10. Allergy in severe asthma.

    PubMed

    Del Giacco, S R; Bakirtas, A; Bel, E; Custovic, A; Diamant, Z; Hamelmann, E; Heffler, E; Kalayci, Ö; Saglani, S; Sergejeva, S; Seys, S; Simpson, A; Bjermer, L

    2017-02-01

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. ADIPONECTIN IN SEVERE PREECLAMPSIA

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods This case-control study included two groups: (1) patients with severe preeclampsia (n=50) and (2) patients with normal pregnancies (n=150). Pulsed-wave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolically-altered, anti-angiogenic and pro-atherogenic state of severe preeclampsia. PMID:17919115

  12. AIDS control: TN may show the way.

    PubMed

    1999-04-19

    The successful experiences of Tamil Nadu (TN) in the control and prevention of HIV/AIDS provides vital clues for the second phase of the Rs. 1,150-crore World Bank-funded national AIDS control program which will begin in July. The National AIDS Control Organization (NACO) is looking at TN for concrete answers in several areas before it composes its guidelines for the second phase. Key areas of focus in the second phase will be high-risk groups, control of STDs, people living with AIDS, communication structures and blood safety. NACO and the funding agency has been impressed by TN¿s method of mobilizing NGOs in the massive anti-HIV/AIDS campaign and its handling of the cost of the care. In addition to the Tamil Nadu State AIDS Control Society (TNSACS), the AIDS Prevention and Control Project of the Voluntary Health Services (supported by USAID) also contributed to the impressive performance of this State.

  13. Remote sensing of volcanic clouds shows promise

    NASA Astrophysics Data System (ADS)

    Rose, William I.

    An international workshop on the Remote Sensing of Volcanic Clouds was held July 29-August 3, 2001, at Michigan Technological University The workshop's goal was to improve and expand the use of satellite-based remote sensing data for hazard mitigation and other research purposes, such as volcano-atmosphere interactions and chemical and meteorological effects on the troposphere and stratosphere. Forty-six researchers attended, representing 11 countries, 9 universities, and several government meteorological and volcanological organizations, as well as the Volcanic Ash Aviation Centers in Washington, D.C., Anchorage, Montreal, Darwin, London, and Toulouse. (The Volcanic Ash Aviation Centers monitor volcanic ash plumes within their assigned airspace. There are 9 in all and they were created at the request of the International Civil Aviation Organization (ICAO) and other aviation concerns.)

  14. 14. INTERIOR OF 1903 POWERHOUSE SHOWING TURBINEGENERATOR UNIT NO. 18, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. INTERIOR OF 1903 POWERHOUSE SHOWING TURBINE-GENERATOR UNIT NO. 18, MANUFACTURED BY GENERAL ELECTRIC IN 1949 AND RATED AT 150 MEGAWATTS. IT WAS RETIRED FROM SERVICE SEVERAL YEARS AGO. - Commonwealth Electric Company, Fisk Street Electrical Generating Station, 1111 West Cermak Avenue, Chicago, Cook County, IL

  15. 48. Detail of top of wall in S room showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    48. Detail of top of wall in S room showing strap-iron beam tie-back anchored in wall with severely deteriorated beam in place. - Hacienda Azurarera Santa Elena, Sugar Mill Ruins, 1.44 miles North of PR Route 2 Bridge Over Rio De La Plata, Toa Baja, Toa Baja Municipio, PR

  16. This image, looking due south shows the central part of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    This image, looking due south shows the central part of the north wing of the building, a 2 story facade. In the foreground are several utility chases which span this elevation of the building - Department of Energy, Mound Facility, Electronics Laboratory Building (E Building), One Mound Road, Miamisburg, Montgomery County, OH

  17. Apolipoprotein A-I: A Molecule of Diverse Function.

    PubMed

    Mangaraj, Manaswini; Nanda, Rachita; Panda, Suchismita

    2016-07-01

    Apolipoprotein A-I (apo A-I) an indispensable component and a major structural protein of high-density lipoprotein (HDL), plays a vital role in reverse cholesterol transport and cellular cholesterol homeostasis since its identification. Its multifunctional role in immunity, inflammation, apoptosis, viral, bacterial infection etc. has crossed its boundary of its potential of protecting cardiovascular system and lowering cardiovascular disease risk, attributing HDL to be known as a protective fat removal particle. Its structural homology with prostacyclin stabilization factor has contributed to its anti-clotting and anti-aggregatory effect on platelet which has potentiated its cardio-protective role as well as its therapeutic efficacy against Alzheimer's disease. The binding affinity and neutralising action against endotoxin lipopolysaccharide, reduces the toxic manifestations of septic shock. As a negative acute phase protein, it blocks T-cell signalling of macrophages. However the recently identified anti-tumor activity of apo A-I has been highlighted in various models of melanoma, lung cancer, ovarian cancer, lymphoblastic leukaemia, gastric as well as pancreatic cancers. These cancer fighting effects are directed towards regression of tumor size and distant metastasis by its immuno modulatory activity as well as its clearing effect on serum lysophospholipids. This lowering effect on lysophospholipid concentration is utilized by apo A-I mimetic peptides to be used in retarding tumor cell proliferation and as a potential cancer therapeutic agent. Not only that, it inhibits the tumor associated neo-angiogenesis as well as brings down the matrix degrading enzymes associated with tumor metastasis. However this efficient therapeutic potential of apo A-I as an anti tumor agent awaits further future experimental studies in humans.

  18. Laser entertainment and light shows in education

    NASA Astrophysics Data System (ADS)

    Sabaratnam, Andrew T.; Symons, Charles

    2002-05-01

    Laser shows and beam effects have been a source of entertainment since its first public performance May 9, 1969, at Mills College in Oakland, California. Since 1997, the Photonics Center, NgeeAnn Polytechnic, Singapore, has been using laser shows as a teaching tool. Students are able to exhibit their creative skills and learn at the same time how lasers are used in the entertainment industry. Students will acquire a number of skills including handling three- phase power supply, operation of cooling system, and laser alignment. Students also acquire an appreciation of the arts, learning about shapes and contours as they develop graphics for the shows. After holography, laser show animation provides a combination of the arts and technology. This paper aims to briefly describe how a krypton-argon laser, galvanometer scanners, a polychromatic acousto-optic modulator and related electronics are put together to develop a laser projector. The paper also describes how students are trained to make their own laser animation and beam effects with music, and at the same time have an appreciation of the operation of a Class IV laser and the handling of optical components.

  19. State Data Show Gains in Reading

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2007-01-01

    Schools taking part in the federal Reading First program are showing significant progress in boosting students' reading fluency and comprehension, according to state-reported data compiled and released by the U.S. Department of Education last week. In releasing for the first time detailed, multiyear data on how Reading First schools are performing…

  20. See you at London Vet Show.

    PubMed

    2016-11-05

    London Vet Show is fast approaching: it takes place from November 17 to 18 and is being held at ExCeL London for the first time. Zoe Davies, marketing manager, highlights some of what BVA is offering at the event. British Veterinary Association.

  1. Showing R-Rated Videos in School.

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    1999-01-01

    Since 1990, there have been at least six published court decisions concerning teachers' use of controversial videos in public schools. A relevant district policy led the Colorado Supreme Court to uphold a teacher's termination for showing 12th graders an R-rated 1900 Bertolucci film on fascism. Implications are discussed. (MLH)

  2. A Talk Show from the Past.

    ERIC Educational Resources Information Center

    Gallagher, Arlene F.

    1991-01-01

    Describes a two-day activity in which elementary students examine voting rights, the right to assemble, and women's suffrage. Explains the game, "Assemble, Reassemble," and a student-produced talk show with five students playing the roles of leaders of the women's suffrage movement. Profiles Elizabeth Cady Stanton, Lucretia Mott, Susan…

  3. State Data Show Gains in Reading

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2007-01-01

    Schools taking part in the federal Reading First program are showing significant progress in boosting students' reading fluency and comprehension, according to state-reported data compiled and released by the U.S. Department of Education last week. In releasing for the first time detailed, multiyear data on how Reading First schools are performing…

  4. Tilapia show immunization response against Ich

    USDA-ARS?s Scientific Manuscript database

    This study compares the immune response of Nile tilapia and red tilapia against parasite Ichthyophthirius multifiliis (Ich) using a cohabitation challenge model. Both Nile and red tilapia showed strong immune response post immunization with live Ich theronts by IP injection or immersion. Blood serum...

  5. Showing Enantiomorphous Crystals of Tartaric Acid

    ERIC Educational Resources Information Center

    Andrade-Gamboa, Julio

    2007-01-01

    Most of the articles and textbooks that show drawings of enantiomorphous crystals use an inadequate view to appreciate the fact that they are non-superimposable mirror images of one another. If a graphical presentation of crystal chirality is not evident, the main attribute of crystal enantiomorphism can not be recognized by students. The classic…

  6. Show Them You Really Want the Job

    ERIC Educational Resources Information Center

    Perlmutter, David D.

    2012-01-01

    Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

  7. EFFECT OF REPETITIVE FILM SHOWINGS ON LEARNING.

    ERIC Educational Resources Information Center

    MCTAVISH, C.L.; AND OTHERS

    A DETERMINATION OF THE INCREMENT IN LEARNING ATTRIBUTABLE SOLELY TO ONE, TWO, AND THREE REPETITIONS OF A FILM OVER AND ABOVE A SINGLE SHOWING WAS INVESTIGATED. THE SUBJECTS WERE 319 COLLEGE FRESHMEN WHO WERE DIVIDED INTO FOUR GROUPS AND WHO WERE SHOWN FOUR GENERAL SCIENCE FILMS. EACH GROUP SAW ONE OF THE FILMS ONCE, A SECOND FILM TWICE, A THIRD…

  8. Show Them You Really Want the Job

    ERIC Educational Resources Information Center

    Perlmutter, David D.

    2012-01-01

    Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

  9. A Talk Show from the Past.

    ERIC Educational Resources Information Center

    Gallagher, Arlene F.

    1991-01-01

    Describes a two-day activity in which elementary students examine voting rights, the right to assemble, and women's suffrage. Explains the game, "Assemble, Reassemble," and a student-produced talk show with five students playing the roles of leaders of the women's suffrage movement. Profiles Elizabeth Cady Stanton, Lucretia Mott, Susan…

  10. Showing Enantiomorphous Crystals of Tartaric Acid

    ERIC Educational Resources Information Center

    Andrade-Gamboa, Julio

    2007-01-01

    Most of the articles and textbooks that show drawings of enantiomorphous crystals use an inadequate view to appreciate the fact that they are non-superimposable mirror images of one another. If a graphical presentation of crystal chirality is not evident, the main attribute of crystal enantiomorphism can not be recognized by students. The classic…

  11. Study Shows Bachelors' Job Situation Improves

    ERIC Educational Resources Information Center

    Physics Today, 1978

    1978-01-01

    The survey shows a definite improvement in the number of jobs which were available for the holders of a Bachelors' Degree in Physics and Astronomy in 1967-77 as compared to 1968-69. The number of students majoring in physics and astronomy is on the rise, and many of them pursue graduate programs in those fields. (GA)

  12. Formation of stable nanodiscs by bihelical apolipoprotein A-I mimetic peptide.

    PubMed

    Kariyazono, Hirokazu; Nadai, Ryo; Miyajima, Rin; Takechi-Haraya, Yuki; Baba, Teruhiko; Shigenaga, Akira; Okuhira, Keiichiro; Otaka, Akira; Saito, Hiroyuki

    2016-02-01

    Nanodiscs are composed of scaffold protein or peptide such as apolipoprotein A-I (apoA-I) and phospholipids. Although peptide-based nanodiscs have an advantage to modulate the size of nanodiscs by changing phospholipid/peptide ratios, they are usually less stable than apoA-I-based nanodiscs. In this study, we designed a novel nanodisc scaffold peptide (NSP) that has proline-punctuated bihelical amphipathic structure based on apoA-I mimetic peptides. NSP formed α-helical structure on 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) nanodiscs prepared by cholate dialysis method. Dynamic light scattering measurements demonstrated that diameters of NSP nanodiscs vary depending upon POPC/NSP ratios. Comparison of thermal unfolding of nanodiscs monitored by circular dichroism measurements demonstrated that NSP forms much more stable nanodiscs with POPC than monohelical peptide, 4F, exhibiting comparable stability to apoA-I-POPC nanodiscs. Intrinsic Trp fluorescence measurements showed that Trp residues of NSP exhibit more hydrophobic environment than that of 4 F on nanodiscs, suggesting the stronger interaction of NSP with phospholipids. Thus, the bihelical structure of NSP appears to increase the stability of nanodiscs because of the enhanced interaction of peptides with phospholipids. In addition, NSP as well as 4F spontaneously solubilized POPC vesicles into nanodiscs without using detergent. These results indicate that bihelical NSP forms nanodiscs with comparable stability to apoA-I and has an ability to control the size of nanodiscs simply by changing phospholipid/peptide ratios. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  13. Immunolocalization of cubilin, megalin, apolipoprotein J, and apolipoprotein A-I in the uterus and oviduct.

    PubMed

    Argraves, W Scott; Morales, Carlos R

    2004-12-01

    Spermatozoa maturation and capacitation occurring in the male and female reproductive tracts, respectively, involves the remodeling of the spermatozoa plasma membrane. Apolipoprotein J (apoJ) and apolipoprotein A-I (apoA-I) have been implicated in the process of lipid exchange from the spermatozoa plasma membrane to epithelial cells lining the male reproductive tract. Evidence suggests that this process is mediated by the cooperative action of the endocytic lipoprotein receptors megalin and cubilin, which are expressed at the apical surface of absorptive epithelia in various tissues, including the efferent ducts and epididymis. Here, we investigated the possibility that these receptors and their lipid-binding ligands, apoJ and apoA-I, might function similarly in the female reproductive tract. We show that megalin and cubilin are expressed in the uterine epithelium at all stages of the estrous cycle, maximally during estrous and metestrous stages. In the oviduct, there is pronounced expression of both megalin and cubilin in the nonciliated cells of the proximal oviduct and epithelial cells of the distal oviduct, particularly during estrous and metestrous stages. In both uterine and oviduct epithelial cells, megalin and cubilin were located on the apical regions of the cells, consistent with a distribution at the cell surface and in endosomes. ApoJ and apoA-I were both detected in apical regions of uterine and oviduct epithelial cells. Secretory cells of the uterine glands were found to express apoJ and apoA-I suggesting that the glands are a site of synthesis for both proteins. In summary, our findings indicate that megalin and cubilin function within the female reproductive tract, possibly mediating uterine and oviduct epithelial cell endocytosis of apoJ/apoA-I-lipid complexes and thus playing a role in lipid efflux from the sperm plasma membrane, a major initiator of capacitation.

  14. Severe aortic stenosis: forgotten associations.

    PubMed

    Godinho, Ana Rita; Amorim, Sandra; Campelo, Manuel; Martins, Elisabete; Lopez Rodriguez, Elisa; Coelho, Rosa; Macedo, Guilherme; Maciel, Maria Júlia

    2014-09-01

    The authors present the case of a 68-year-old man with predominantly right heart failure in the context of severe aortic stenosis associated with pulmonary hypertension. Anemia was diagnosed which, after endoscopic study, was considered to be secondary to angiodysplasia and a diagnosis of Heyde syndrome was made. After valve replacement surgery the patient's heart failure improved and hemoglobin levels stabilized. We present this case to show the need to recognize less common associations of severe aortic stenosis, in order to provide immediate and appropriate treatment.

  15. Male genital leiomyomas showing androgen receptor expression.

    PubMed

    Suárez-Peñaranda, José Manuel; Vieites, Begoña; Evgenyeva, Elena; Vázquez-Veiga, Hugo; Forteza, Jeronimo

    2007-12-01

    Genital leiomyoma in men include those superficial leiomyomas arising in the scrotum and the areola. They are unusual neoplasms: few cases have been reported in the literature and they usually escape clinical diagnosis. Three cases of male genital leiomyomas are reported: two in the scrotum and one in the areola. They were all conservatively excised and the behaviour was completely benign in all cases. Histopathological examination showed the typical findings of superficial leiomyomas, with some minor differences between cases arising in the scrotum and those from the areola. Immunohistochemical findings not only confirmed the smooth muscle nature of all cases but also showed unequivocal immunostaining for androgen receptors in the leiomyomas from the scrotum. Immunostaining for androgen receptors in scrotal leiomyomas is, as far as we are aware, a previously unknown characteristic of male genital leiomyomas. This finding supports the role of steroid hormones in the growth of genital leiomyomas, similar to leiomyomas found in other locations.

  16. Human platelet sulfotransferase shows seasonal rhythms.

    PubMed

    Marazziti, D; Palego, L; Mazzanti, C; Silvestri, S; Cassano, G B

    1995-04-01

    Our study aimed to investigate the possible presence of seasonal changes in platelet phenolsulfotransferase (ST) in a group of 20 healthy, drug-free subjects of both sexes between 24 and 37 years of age. Blood samples were taken four times a year in the period immediately following the equinoxes and the solstices. The results showed that both Sts underwent seasonal changes: the lowest values were found in autumn and in winter, and the highest in the summer. A positive correlation between the two STs and the length of the photoperiod was observed in winter whereas in the spring we detected a negative correlation between the TL ST and the photoperiod length. Future studies should clarify whether platelet ST of patients with mood disorders shows a similar seasonality.

  17. Study shows gasohol ups car emissions

    SciTech Connect

    Not Available

    1980-04-04

    Evaporative emissions by cars using gasohol were examined by General Motors Corp. The study showed an increase in emissions by as much as 51% over cars using unleaded gasoline. It is stated that cold-start driveability was worse with gasohol and there was a 0.9 to 3.7% decrease in fuel economy. The use of gasohol, however, did produce lower HC, CO and NO exhaust emissions than gasoline.

  18. [Severe depression : psychoanalysis].

    PubMed

    Bouvet de la Maisonneuve, O

    2009-12-01

    The indication for psychoanalysis in severe depression is not clear. And yet, demands for this type of intervention are increasing, despite the absence of any form of consensus on the subject. Freud considered depression as a failure of analytical efforts and, based on this observation, revised his theory, in particular to include the notions of narcissism and the death drive. Many analysts have been reluctant to follow his teachings on this last point and provide depressed patients with analytical-type therapies aimed at restoring narcissism. Melanie Klein pushed Freud's ideas about depression even further and brought such therapies back to the heart of analytical practice. Jacques Lacan took the debate to another level by proposing an overhaul of the principles on which analysis has been based. Today, while following certain precautionary rules, true psychoanalyses can be proposed to patients with severe depression, whether of the bipolar, recurring or even neurotic type that can reach this level of severity.

  19. Severe Weather training

    NASA Astrophysics Data System (ADS)

    Ter Pelkwijk, H.

    2009-09-01

    Our environmental models, such as the models we use for weather prediction, are getting better and better. Within the operational meteorology there is a growing tendency to use models to produce automatic forecasts. For the forecaster this means more work is done on a weather dependent base and less routine work. An example of weather dependent work is the analysis of severe weather events. These will not occur very often, and when they occur different people will be on shift. This means a small chance to gain expertise in this field which becomes more and more complex. Within KNMI we have made a Severe Weather Catalogue which we can use to train the forecaster. In this presentation I will tell something about the ideas behind the Severe Weather Catalogue, how it works, the training of the forecasters and the problems we face.

  20. Software for portable laser light show system

    NASA Astrophysics Data System (ADS)

    Buruchin, Dmitrey J.; Leonov, Alexander F.

    1995-04-01

    Portable laser light show system LS-3500-10M is connected to the parallel port of IBM PC/AT compatible computer. Computer performs output of digital control data describing images. Specially designed control device is used to convert digital data coming from parallel port to the analog signal driving scanner. Capabilities of even cost nothing 286 computer are quite enough for laser graphics control. Technology of scanning used in laser graphics system LS-3500-10M essentially differs from widely spread systems based on galvanometers with mobile core or with mobile magnet. Such devices are based on the same principle of work as electrically driven servo-mechanism. As scanner we use elastic system with hydraulic dampen oscillations and opened loop. For most of applications of laser graphics such system provides satisfactory precision and speed of scanning. LS-3500-10M software gives user ability to create on PC and play his own laser graphics demonstrations. It is possible to render recognizable text and pictures using different styles, 3D and abstract animation. All types of demonstrations can be mixed in slide-show. Time synchronization is supported. Software has the following features: (1) Different types of text output. Built-in text editor for typing and editing of textural information. Different fonts can be used to display text. User can create his own fonts using specially developed font editor. (2) Editor of 3D animation with library of predefined shapes. (3) Abstract animation provided by software routines. (4) Support of different graphics files formats (PCX or DXF). Original algorithm of raster image tracing was implemented. (5) Built-in slide-show editor.

  1. Latest European coelacanth shows Gondwanan affinities.

    PubMed

    Cavin, Lionel; Forey, Peter L; Buffetaut, Eric; Tong, Haiyan

    2005-06-22

    The last European fossil occurrence of a coelacanth is from the Mid-Cretaceous of the English Chalk (Turonian, 90 million years ago). Here, we report the discovery of a coelacanth from Late Cretaceous non-marine rocks in southern France. It consists of a left angular bone showing structures that imply close phylogenetic affinities with some extinct Mawsoniidae. The closest relatives are otherwise known from Cretaceous continental deposits of southern continents and suggest that the dispersal of freshwater organisms from Africa to Europe occurred in the Late Cretaceous.

  2. Molars and incisors: show your microarray IDs

    PubMed Central

    2013-01-01

    Background One of the key questions in developmental biology is how, from a relatively small number of conserved signaling pathways, is it possible to generate organs displaying a wide range of shapes, tissue organization, and function. The dentition and its distinct specific tooth types represent a valuable system to address the issues of differential molecular signatures. To identify such signatures, we performed a comparative transcriptomic analysis of developing murine lower incisors, mandibular molars and maxillary molars at the developmental cap stage (E14.5). Results 231 genes were identified as being differentially expressed between mandibular incisors and molars, with a fold change higher than 2 and a false discovery rate lower than 0.1, whereas only 96 genes were discovered as being differentially expressed between mandibular and maxillary molars. Numerous genes belonging to specific signaling pathways (the Hedgehog, Notch, Wnt, FGF, TGFβ/BMP, and retinoic acid pathways), and/or to the homeobox gene superfamily, were also uncovered when a less stringent fold change threshold was used. Differential expressions for 10 out of 12 (mandibular incisors versus molars) and 9 out of 10 selected genes were confirmed by quantitative reverse transcription-PCR (qRT-PCR). A bioinformatics tool (Ingenuity Pathway Analysis) used to analyze biological functions and pathways on the group of incisor versus molar differentially expressed genes revealed that 143 genes belonged to 9 networks with intermolecular connections. Networks with the highest significance scores were centered on the TNF/NFκB complex and the ERK1/2 kinases. Two networks ERK1/2 kinases and tretinoin were involved in differential molar morphogenesis. Conclusion These data allowed us to build several regulatory networks that may distinguish incisor versus molar identity, and may be useful for further investigations of these tooth-specific ontogenetic programs. These programs may be dysregulated in

  3. Show Me the Invisible: Visualizing Hidden Content

    PubMed Central

    Geymayer, Thomas; Steinberger, Markus; Lex, Alexander; Streit, Marc; Schmalstieg, Dieter

    2014-01-01

    Content on computer screens is often inaccessible to users because it is hidden, e.g., occluded by other windows, outside the viewport, or overlooked. In search tasks, the efficient retrieval of sought content is important. Current software, however, only provides limited support to visualize hidden occurrences and rarely supports search synchronization crossing application boundaries. To remedy this situation, we introduce two novel visualization methods to guide users to hidden content. Our first method generates awareness for occluded or out-of-viewport content using see-through visualization. For content that is either outside the screen’s viewport or for data sources not opened at all, our second method shows off-screen indicators and an on-demand smart preview. To reduce the chances of overlooking content, we use visual links, i.e., visible edges, to connect the visible content or the visible representations of the hidden content. We show the validity of our methods in a user study, which demonstrates that our technique enables a faster localization of hidden content compared to traditional search functionality and thereby assists users in information retrieval tasks. PMID:25325078

  4. Severe blastomycosis in infants.

    PubMed

    Pelly, Lorine; Al Juaid, Alaa; Fanella, Sergio

    2014-11-01

    Blastomycosis is a dimorphic fungal infection that can be manifested as pulmonary or extrapulmonary disease. Disease in infants is rare, even in endemic areas. We report a case of severe blastomycosis in a 4-month-old infant, as well as details of 2 other cases from our center and a brief review of infant blastomycosis.

  5. [Severe psoriasis: 160 cases].

    PubMed

    Jalal, O; Houass, S; Laissaoui, K; Hocar, O; Charioui, S; Amal, S

    2005-02-01

    Psoriasis is a frequent dermatosis, its prevalence is estimated of between 1 and 3 p. 100. The severe forms may threaten the functional and life prognosis of patients. We conducted a retrospective study on 160 cases of severe psoriasis collected between 1990 and 2001. We included patients exhibiting severe psoriasis: pustular, erythrodermic or arthropathic psoriasis, the generalized forms that had developed for more than 6 months, without positive response to treatment and the forms with a PASI greater than 50. The patients' ages ranged from 6 to 85 years with a clear male predominance (96 men, 64 women). Nine familial cases were collected. Erythroderma was noted in 87 cases, pustular psoriasis in 31, generalized psoriasis in 31 and psoriatic rheumatism in 15 (4 of which were associated with pustular psoriasis). Local treatment with topical corticosteroids or a Vitamin D derivative was recommended in respectively 41.8 and 13.75 p. 100 of cases. The administration of general treated relied on methotrexate and was required in 68.75 p. 100 of cases. Progression was usually good, relapses were often noted when treatment was stopped. Four patients died. Although the diagnosis of psoriasis is often easy, the severe forms are still difficult to treat. Treatment is complicated, sometimes disappointing and often necessitates heavy and aggressive treatments that require strict surveillance.

  6. Severe storms forecast systems

    NASA Technical Reports Server (NTRS)

    Kaplan, M.; Zack, J.

    1980-01-01

    Two research tasks are described: (1) the improvement and enhancement of an existing mesoscale numerical simulation system, and (2) numerical diagnostic studies associated with an individual case of severe storm development (April 10, 1979 in the Red River Valley of Texas and Oklahoma).

  7. Lemurs and macaques show similar numerical sensitivity

    PubMed Central

    Jones, Sarah M.; Pearson, John; DeWind, Nicholas K.; Paulsen, David; Tenekedjieva, Ana-Maria; Brannon, Elizabeth M.

    2013-01-01

    We investigated the precision of the approximate number system (ANS) in three lemur species (Lemur catta, Eulemur mongoz, and Eulemur macaco flavifrons), one Old World monkey species (Macaca mulatta) and humans (Homo sapiens). In Experiment 1, four individuals of each nonhuman primate species were trained to select the numerically larger of two visual arrays on a touchscreen. We estimated numerical acuity by modeling Weber fractions (w) and found quantitatively equivalent performance among all four nonhuman primate species. In Experiment 2, we tested adult humans in a similar procedure, and they outperformed the four nonhuman species but showed qualitatively similar performance. These results indicate that the ANS is conserved over the primate order. PMID:24068469

  8. Surveys show support for green 'activities'.

    PubMed

    Baillie, Jonathan

    2012-03-01

    Two independently conducted surveys on sustainability - one into the 'views and values' of NHS 'leaders', and the other questioning the public about the importance of the 'green agenda' in the NHS, and their opinions on how the service might most effectively reduce its carbon footprint, form the basis of Sustainability in the NHS: Health Check 2012, a new NHS Sustainable Development Unit (NHS SDU) publication. As HEJ editor Jonathan Baillie reports, the new document also presents updated data on the 'size' of the carbon footprint of the NHS in England, showing that, although good work by a number of Trusts in the past two years has seen healthcare-generated carbon emissions start to 'level off', the biggest contributors have been the current health service spending review, and the increased national availability of renewable energy.

  9. Microbiological and environmental issues in show caves.

    PubMed

    Saiz-Jimenez, Cesareo

    2012-07-01

    Cultural tourism expanded in the last half of the twentieth century, and the interest of visitors has come to include caves containing archaeological remains. Some show caves attracted mass tourism, and economical interests prevailed over conservation, which led to a deterioration of the subterranean environment and the rock art. The presence and the role of microorganisms in caves is a topic that is often ignored in cave management. Knowledge of the colonisation patterns, the dispersion mechanisms, and the effect on human health and, when present, over rock art paintings of these microorganisms is of the utmost importance. In this review the most recent advances in the study of microorganisms in caves are presented, together with the environmental implications of the findings.

  10. Mesenchymal stem cells show radioresistance in vivo.

    PubMed

    Singh, Sarvpreet; Kloss, Frank R; Brunauer, Regina; Schimke, Magdalena; Jamnig, Angelika; Greiderer-Kleinlercher, Brigitte; Klima, Günter; Rentenberger, Julia; Auberger, Thomas; Hächl, Oliver; Rasse, Michael; Gassner, Robert; Lepperdinger, Günter

    2012-04-01

    Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.

  11. Ghrelin levels increase after pictures showing food.

    PubMed

    Schüssler, Petra; Kluge, Michael; Yassouridis, Alexander; Dresler, Martin; Uhr, Manfred; Steiger, Axel

    2012-06-01

    The neuropeptide ghrelin is a major signal for food intake in various species including humans. After exogenous ghrelin administration, food intake and body weight increase in rodents. In normal human subjects, ghrelin administration increases self-rated appetite and calorie intake and prompts the imagination of favorite meals. It is unclear so far whether ghrelin levels are affected by external cues such as sight of food. We investigated the influence of pictures showing food compared to neutral pictures on ghrelin levels in young normal male subjects (n = 8). The study consisted of two consecutive sessions with a one-week interval. During each session, blood for later analysis of plasma concentrations of ghrelin was collected between 08:15 and 13:00 every 15 min (between 10:30 and 11:30 every 10 min). Breakfast and lunch was provided at 08:30 and 12:00, respectively. Fifty pictures were presented from 10:30 to 10:45 showing neutral images during the first session and food contents during the second session. As expected, ghrelin levels increased before each meal independent of the picture contents. In addition, ghrelin levels during the 30-min interval following the presentation of pictures with food increased significantly compared to the 30-min interval before this presentation (area under the curve (AUC): 188 % vs. 158 %, P < 0.05). The difference in the increases between the two picture conditions was also significant (P < 0.05). Our findings suggest that sight of food elevates ghrelin levels in healthy volunteers.

  12. [Separation and purification of human apolipoproteins A-I and C-III by chromatofocusing].

    PubMed

    Cheng, B

    1993-08-01

    Human very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were isolated and purified by a process of combined dextran sulfate precipitation and density gradient ultracentrifugation. Chromatofocusing, which separates protein based on differences in isoelectric point, was used to separate apolipoprotein A-I (apoA-I) and apolipoprotein C-III from human HDL and VLDL, respectively. Discontinuous SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and analytical isoelectric focusing (IEF) were used to study the purity of different fractions. Both purified apoA-I and apoC-III showed single bands on SDS-PAGE at molecular weights of 28183 and 9400 Daltons, respectively. As determined by IEF in the presence of 8 mol/L urea, apoA-I had eight isoforms with pI of 5.66-5.87. The pI's of the three isoproteins of apoC-III (C-III0, C-III1 and C-III2) were 5.06, 4.88 and 4.72, respectively. Chromatofocusing, a new simple technique combining the high resolving power of IEF with the high capacity of ion-exchange column chromatography, is extremely valuable for large-scale purification of the major apolipoproteins of VLDL and HDL.

  13. Accretion Discs Show Their True Colours

    NASA Astrophysics Data System (ADS)

    2008-07-01

    Desert, in Chile, as well as several other telescopes, including STFC's UKIRT. The standard picture of the accretion disc is therefore vindicated. The authors believe that further measurements could eventually provide valuable insight into how and where the disc ends, and how material is being supplied to the disc.

  14. Cassini UVIS Observations Show Active Saturn's Rings

    NASA Astrophysics Data System (ADS)

    Esposito, L.; Colwell, J. E.; UVIS Team

    2004-12-01

    interior of such a body has been shielded from external meteoritic bombardment, and thus contains purer ice. Since the amount of meteoroid pollution provides a rough clock to estimate the age of the rings (Cuzzi and Estrada), these random events reset that clock locally, making the material at that radial location younger and purer. As these purer ring particles collide with others, they exchange regolith, and the range of purer water ice spectrum spreads radially. The radial variation we interpret as due to differential pollution in our data set is consistent with the disruption of several small bodies in the A ring in the last 107 to 108 years. When the small moon Pan (Showalter 1991, R ~ 10 km, now residing in the nearby Encke Gap) is eventually shattered by an external impact (Colwell et al 2000), the gap will close up, and for some 10 to 100 million years thereafter a brighter radial swath of purer water ice at its former location will gradually spread and darken.

  15. Temperature Data Shows Warming in 2001

    NASA Technical Reports Server (NTRS)

    2002-01-01

    TThe figure above depicts how much air temperatures near the Earth's surface changed relative to the global mean temperature from 1951 to 1980. NASA researchers used maps of urban areas derived from city lights data to account for the 'heat island' effect of cities. The red and orange colors show that temperatures are warmer in most regions of the world when compared to the 1951 to 1980 'normal' temperatures. Warming around the world has been widespread, but it is not present everywhere. The largest warming is in Northern Canada, Alaska and Siberia, as indicated by the deeper red colors. The lower 48 United States have become warmer recently, but only enough to make the temperatures comparable to what they were in the 1930s. The scale on the bottom of these temperature anomaly images represent degrees in Celsius. The negative numbers represent cooling and the positive numbers depict warming. Overall, the air temperature near the Earth's surface has warmed by 1oF (0.6oC) globally, on average, over the last century. For more information and additional images, read Satellites Shed Light on a Warmer World. Image courtesy Goddard Institute for Space Studies (GISS).

  16. Temperature Data Shows Warming in 2001

    NASA Technical Reports Server (NTRS)

    2002-01-01

    TThe figure above depicts how much air temperatures near the Earth's surface changed relative to the global mean temperature from 1951 to 1980. NASA researchers used maps of urban areas derived from city lights data to account for the 'heat island' effect of cities. The red and orange colors show that temperatures are warmer in most regions of the world when compared to the 1951 to 1980 'normal' temperatures. Warming around the world has been widespread, but it is not present everywhere. The largest warming is in Northern Canada, Alaska and Siberia, as indicated by the deeper red colors. The lower 48 United States have become warmer recently, but only enough to make the temperatures comparable to what they were in the 1930s. The scale on the bottom of these temperature anomaly images represent degrees in Celsius. The negative numbers represent cooling and the positive numbers depict warming. Overall, the air temperature near the Earth's surface has warmed by 1oF (0.6oC) globally, on average, over the last century. For more information and additional images, read Satellites Shed Light on a Warmer World. Image courtesy Goddard Institute for Space Studies (GISS).

  17. First K2 mutiplanatary system showing TTVs

    NASA Astrophysics Data System (ADS)

    Barros, Susana C. C.

    2015-08-01

    In traditional transit timing variations (TTVs) analysis of multi-planetary systems, the individual TTVs are first derived from transit fitting and later modeled using n-body dynamic simulations to constrain planetary masses.I will show that fitting simultaneously the transit light curves with the system dynamics (photo-dynamical model) increases the precision of the TTV measurements and helps constrain the system architecture. I will exemplify the advantages of applying this photo-dynamical model to a multi-planetary system found in K2 data very close to 3:2 mean motion resonance. In this case the period of the larger TTV variations (libration period) is much longer (~1.5 years) than the duration of the K2 observations (~80 days). However, our method allows to detect the short period TTVs produced by the orbital conjunctions between the planets that in turn permits to uniquely characterize the system. Therefore, our method can be used to constrain the masses of near-resonant systems even when the full libration curve is not observed and hence will help understanding evolution of these interesting systems.

  18. Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase.

    PubMed

    Thöny, Beat; Calvo, Ana C; Scherer, Tanja; Svebak, Randi M; Haavik, Jan; Blau, Nenad; Martinez, Aurora

    2008-07-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters. Primary inherited defects in TH have been associated with l-DOPA responsive and non-responsive dystonia and infantile parkinsonism. In this study, we show that both the cofactor (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro. Activity measurements and synthesis of the enzyme by in vitro transcription-translation revealed a complex regulation by the cofactor including both enzyme inactivation and conformational stabilization. Oral BH(4) supplementation to mice increased TH activity and protein levels in brain extracts, while the Th-mRNA level was not affected. All together our results indicate that the molecular mechanisms for the stabilization are a primary folding-aid effect of BH(4) and a secondary effect by increased synthesis and binding of catecholamine ligands. Our results also establish that orally administered BH(4) crosses the blood-brain barrier and therapeutic regimes based on BH(4) supplementation should thus consider the effect on TH. Furthermore, BH(4) supplementation arises as a putative therapeutic agent in the treatment of brain disorders associated with TH misfolding, such as for the human TH isoform 1 mutation L205P.

  19. NASA GIBS Use in Live Planetarium Shows

    NASA Astrophysics Data System (ADS)

    Emmart, C. B.

    2015-12-01

    The American Museum of Natural History's Hayden Planetarium was rebuilt in year 2000 as an immersive theater for scientific data visualization to show the universe in context to our planet. Specific astrophysical movie productions provide the main daily programming, but interactive control software, developed at AMNH allows immersive presentation within a data aggregation of astronomical catalogs called the Digital Universe 3D Atlas. Since 2006, WMS globe browsing capabilities have been built into a software development collaboration with Sweden's Linkoping University (LiU). The resulting Uniview software, now a product of the company SCISS, is operated by about fifty planetariums around that world with ability to network amongst the sites for global presentations. Public presentation of NASA GIBS has allowed authoritative narratives to be presented within the range of data available in context to other sources such as Science on a Sphere, NASA Earth Observatory and Google Earth KML resources. Specifically, the NOAA supported World Views Network conducted a series of presentations across the US that focused on local ecological issues that could then be expanded in the course of presentation to national and global scales of examination. NASA support of for GIBS resources in an easy access multi scale streaming format like WMS has tremendously enabled particularly facile presentations of global monitoring like never before. Global networking of theaters for distributed presentations broadens out the potential for impact of this medium. Archiving and refinement of these presentations has already begun to inform new types of documentary productions that examine pertinent, global interdependency topics.

  20. The earliest published electrocardiogram showing ventricular preexcitation.

    PubMed

    Von Knorre, Georg H

    2005-03-01

    When in 1930, Wolff, Parkinson, and White published what is today known as the WPW, or preexcitation syndrome, they, and subsequently others, found few comparable cases in the preceding literature. Among these the report of Cohn and Fraser, published in 1913, was the earliest. However, another even earlier documentation in a 1909 article by Hoffmann escaped notice till now. The ECG of a patient with paroxysmal tachycardia reveals a short PR interval and a delta-wave-induced widening of the QRS complex, even though the reproduced tachycardia was not preexcitation related. The interpretation of this poorly reproduced ECG can be confirmed by another and more detailed description of the patient in an electrocardiography textbook published in 1914 by the same author. Thus, the earliest publication of an ECG showing ventricular preexcitation now can be dated back to 1909. Moreover, the Hoffmann monograph contains two additional examples of the WPW syndrome not noticed until now. All three cases published by Hoffmann had their first ECG recordings in 1912 or earlier.

  1. The great American medicine show revisited.

    PubMed

    Tomes, Nancy

    2005-01-01

    Since the late 1800s, changes in the advertising and marketing of medicinal drugs have produced heated debates in the United States. With the emergence of the modern prescription drug between 1938 and 1951, concerns that once focused primarily on patients' use of over-the-counter drugs were broadened to include physicians and their "doctors' drugs" as well. The medical profession's growing control over their patients' drug choices inevitably heightened the scrutiny of their own performance as consumers. Although deeply divided over issues of the patient's role in medical decision making, consumer activists and physician reformers expressed similar concerns about the impact of aggressive pharmaceutical marketing and advertising on the doctor-patient relationship, and starting in the late 1950s they employed strikingly similar strategies to counter the new corporate "medicine show." Yet their efforts to promote a more rational use of prescription drugs have usually been too little and too late to offset the effectiveness of pharmaceutical advertising and mar-keting activities.

  2. NASA's SDO Shows Moon Transiting the Sun

    NASA Image and Video Library

    2017-09-28

    On Nov. 22, 2014 from 5:29 to 6:04 p.m. EST., the moon partially obscured the view of the sun from NASA's Solar Dynamics Observatory. This phenomenon, which is called a lunar transit, could only be seen from SDO's point of view. In 2014, SDO captured four such transits -- including its longest ever recorded, which occurred on Jan. 30, and lasted two and a half hours. SDO imagery during a lunar transit always shows a crisp horizon on the moon -- a reflection of the fact that the moon has no atmosphere around it to distort the light from the sun. The horizon is so clear in these images that mountains and valleys in the terrain can be seen. Credit: NASA/SDO NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  3. Ancient bacteria show evidence of DNA repair

    PubMed Central

    Johnson, Sarah Stewart; Hebsgaard, Martin B.; Christensen, Torben R.; Mastepanov, Mikhail; Nielsen, Rasmus; Munch, Kasper; Brand, Tina; Gilbert, M. Thomas P.; Zuber, Maria T.; Bunce, Michael; Rønn, Regin; Gilichinsky, David; Froese, Duane; Willerslev, Eske

    2007-01-01

    Recent claims of cultivable ancient bacteria within sealed environments highlight our limited understanding of the mechanisms behind long-term cell survival. It remains unclear how dormancy, a favored explanation for extended cellular persistence, can cope with spontaneous genomic decay over geological timescales. There has been no direct evidence in ancient microbes for the most likely mechanism, active DNA repair, or for the metabolic activity necessary to sustain it. In this paper, we couple PCR and enzymatic treatment of DNA with direct respiration measurements to investigate long-term survival of bacteria sealed in frozen conditions for up to one million years. Our results show evidence of bacterial survival in samples up to half a million years in age, making this the oldest independently authenticated DNA to date obtained from viable cells. Additionally, we find strong evidence that this long-term survival is closely tied to cellular metabolic activity and DNA repair that over time proves to be superior to dormancy as a mechanism in sustaining bacteria viability. PMID:17728401

  4. Modelling runway incursion severity.

    PubMed

    Wilke, Sabine; Majumdar, Arnab; Ochieng, Washington Y

    2015-06-01

    Analysis of the causes underlying runway incursions is fundamental for the development of effective mitigation measures. However, there are significant weaknesses in the current methods to model these factors. This paper proposes a structured framework for modelling causal factors and their relationship to severity, which includes a description of the airport surface system architecture, establishment of terminological definitions, the determination and collection of appropriate data, the analysis of occurrences for severity and causes, and the execution of a statistical analysis framework. It is implemented in the context of U.S. airports, enabling the identification of a number of priority interventions, including the need for better investigation and causal factor capture, recommendations for airfield design, operating scenarios and technologies, and better training for human operators in the system. The framework is recommended for the analysis of runway incursions to support safety improvements and the methodology is transferable to other areas of aviation safety risk analysis.

  5. Severe low turnover osteoporosis.

    PubMed

    Pietrogrande, Luca

    2007-08-01

    Severe osteoporosis, a situation with fractures, can worsen in the case of poor response to usual therapies, such as bisphosphonates associated with calcium and vitamin D, especially if bone turnover is strongly suppressed. One way of inverting the poor evolution of non-responders is to use Teriparatide. The case of a non-responder is reported, with considerations about the possibility of detecting these patients before a new fracture takes place.

  6. Clinical review: Severe asthma

    PubMed Central

    Papiris, Spyros; Kotanidou, Anastasia; Malagari, Katerina; Roussos, Charis

    2002-01-01

    Severe asthma, although difficult to define, includes all cases of difficult/therapy-resistant disease of all age groups and bears the largest part of morbidity and mortality from asthma. Acute, severe asthma, status asthmaticus, is the more or less rapid but severe asthmatic exacerbation that may not respond to the usual medical treatment. The narrowing of airways causes ventilation perfusion imbalance, lung hyperinflation, and increased work of breathing that may lead to ventilatory muscle fatigue and life-threatening respiratory failure. Treatment for acute, severe asthma includes the administration of oxygen, β2-agonists (by continuous or repetitive nebulisation), and systemic corticosteroids. Subcutaneous administration of epinephrine or terbutaline should be considered in patients not responding adequately to continuous nebulisation, in those unable to cooperate, and in intubated patients not responding to inhaled therapy. The exact time to intubate a patient in status asthmaticus is based mainly on clinical judgment, but intubation should not be delayed once it is deemed necessary. Mechanical ventilation in status asthmaticus supports gas-exchange and unloads ventilatory muscles until aggressive medical treatment improves the functional status of the patient. Patients intubated and mechanically ventilated should be appropriately sedated, but paralytic agents should be avoided. Permissive hypercapnia, increase in expiratory time, and promotion of patient-ventilator synchronism are the mainstay in mechanical ventilation of status asthmaticus. Close monitoring of the patient's condition is necessary to obviate complications and to identify the appropriate time for weaning. Finally, after successful treatment and prior to discharge, a careful strategy for prevention of subsequent asthma attacks is imperative. PMID:11940264

  7. Severe congenital neutropenias.

    PubMed

    Skokowa, Julia; Dale, David C; Touw, Ivo P; Zeidler, Cornelia; Welte, Karl

    2017-06-08

    Severe congenital neutropenias are a heterogeneous group of rare haematological diseases characterized by impaired maturation of neutrophil granulocytes. Patients with severe congenital neutropenia are prone to recurrent, often life-threatening infections beginning in their first months of life. The most frequent pathogenic defects are autosomal dominant mutations in ELANE, which encodes neutrophil elastase, and autosomal recessive mutations in HAX1, whose product contributes to the activation of the granulocyte colony-stimulating factor (G-CSF) signalling pathway. The pathophysiological mechanisms of these conditions are the object of extensive research and are not fully understood. Furthermore, severe congenital neutropenias may predispose to myelodysplastic syndromes or acute myeloid leukaemia. Molecular events in the malignant progression include acquired mutations in CSF3R (encoding G-CSF receptor) and subsequently in other leukaemia-associated genes (such as RUNX1) in a majority of patients. Diagnosis is based on clinical manifestations, blood neutrophil count, bone marrow examination and genetic and immunological analyses. Daily subcutaneous G-CSF administration is the treatment of choice and leads to a substantial increase in blood neutrophil count, reduction of infections and drastic improvement of quality of life. Haematopoietic stem cell transplantation is the alternative treatment. Regular clinical assessments (including yearly bone marrow examinations) to monitor treatment course and detect chromosomal abnormalities (for example, monosomy 7 and trisomy 21) as well as somatic pre-leukaemic mutations are recommended.

  8. Epidemiology of severe trauma.

    PubMed

    Alberdi, F; García, I; Atutxa, L; Zabarte, M

    2014-12-01

    Major injury is the sixth leading cause of death worldwide. Among those under 35 years of age, it is the leading cause of death and disability. Traffic accidents alone are the main cause, fundamentally in low- and middle-income countries. Patients over 65 years of age are an increasingly affected group. For similar levels of injury, these patients have twice the mortality rate of young individuals, due to the existence of important comorbidities and associated treatments, and are more likely to die of medical complications late during hospital admission. No worldwide, standardized definitions exist for documenting, reporting and comparing data on severely injured trauma patients. The most common trauma scores are the Abbreviated Injury Scale (AIS), the Injury Severity Score (ISS) and the Trauma and Injury severity Score (TRISS). Documenting the burden of injury also requires evaluation of the impact of post-trauma impairments, disabilities and handicaps. Trauma epidemiology helps define health service and research priorities, contributes to identify disadvantaged groups, and also facilitates the elaboration of comparable measures for outcome predictions.

  9. Sidekick or star of the show?

    NASA Image and Video Library

    2017-02-13

    This image was captured by the NASA/ESA Hubble Space Telescope’s Advanced Camera for Surveys (ACS), a highly efficient wide-field camera covering the optical and near-infrared parts of the spectrum. While this lovely image contains hundreds of distant stars and galaxies, one vital thing is missing — the object Hubble was actually studying at the time! This is not because the target has disappeared. The ACS actually uses two detectors: the first captures the object being studied — in this case an open star cluster known as NGC 299 — while the other detector images the patch of space just ‘beneath’ it. This is what can be seen here. Technically, this picture is merely a sidekick of the actual object of interest — but space is bursting with activity, and this field of bright celestial bodies offers plenty of interest on its own. It may initially seem to show just stars, but a closer look reveals many of these tiny objects to be galaxies. The spiral galaxies have arms curving out from a bright centre. The fuzzier, less clearly shaped galaxies might be ellipticals. Some of these galaxies contain millions and millions of stars, but are so distant that all of their starry residents are contained within just a small pinprick of light that appears to be the  same size as a single star! The bright blue dots are very hot stars, sometimes distorted into crosses by the struts supporting Hubble’s secondary mirror. The redder dots are cooler stars, possibly in the red giant phase when a dying star cools and expands.

  10. Starving neurons show sex difference in autophagy.

    PubMed

    Du, Lina; Hickey, Robert W; Bayir, Hülya; Watkins, Simon C; Tyurin, Vladimir A; Guo, Fengli; Kochanek, Patrick M; Jenkins, Larry W; Ren, Jin; Gibson, Greg; Chu, Charleen T; Kagan, Valerian E; Clark, Robert S B

    2009-01-23

    Sex-dependent differences in adaptation to famine have long been appreciated, thought to hinge on female versus male preferences for fat versus protein sources, respectively. However, whether these differences can be reduced to neurons, independent of typical nutrient depots, such as adipose tissue, skeletal muscle, and liver, was heretofore unknown. A vital adaptation to starvation is autophagy, a mechanism for recycling amino acids from organelles and proteins. Here we show that segregated neurons from males in culture are more vulnerable to starvation than neurons from females. Nutrient deprivation decreased mitochondrial respiration, increased autophagosome formation, and produced cell death more profoundly in neurons from males versus females. Starvation-induced neuronal death was attenuated by 3-methyladenine, an inhibitor of autophagy; Atg7 knockdown using small interfering RNA; or L-carnitine, essential for transport of fatty acids into mitochondria, all more effective in neurons from males versus females. Relative tolerance to nutrient deprivation in neurons from females was associated with a marked increase in triglyceride and free fatty acid content and a cytosolic phospholipase A2-dependent increase in formation of lipid droplets. Similar sex differences in sensitivity to nutrient deprivation were seen in fibroblasts. However, although inhibition of autophagy using Atg7 small interfering RNA inhibited cell death during starvation in neurons, it increased cell death in fibroblasts, implying that the role of autophagy during starvation is both sex- and tissue-dependent. Thus, during starvation, neurons from males more readily undergo autophagy and die, whereas neurons from females mobilize fatty acids, accumulate triglycerides, form lipid droplets, and survive longer.

  11. DAST in Flight Showing Diverging Wingtip Oscillations

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Two BQM-34 Firebee II drones were modified with supercritical airfoils, called the Aeroelastic Research Wing (ARW), for the Drones for Aerodynamic and Structural Testing (DAST) program, which ran from 1977 to 1983. In this view of DAST-1 (Serial # 72-1557), taken on June 12, 1980, severe wingtip flutter is visible. Moments later, the right wing failed catastrophically and the vehicle crashed near Cuddeback Dry Lake. Before the drone was lost, it had made two captive and two free flights. Its first free flight, on October 2, 1979, was cut short by an uplink receiver failure. The drone was caught in midair by an HH-3 helicopter. The second free flight, on March 12, 1980, was successful, ending in a midair recovery. The third free flight, made on June 12, was to expand the flutter envelope. All of these missions launched from the NASA B-52. From 1977 to 1983, the Dryden Flight Research Center, Edwards, California, (under two different names) conducted the DAST Program as a high-risk flight experiment using a ground-controlled, pilotless aircraft. Described by NASA engineers as a 'wind tunnel in the sky,' the DAST was a specially modified Teledyne-Ryan BQM-34E/F Firebee II supersonic target drone that was flown to validate theoretical predictions under actual flight conditions in a joint project with the Langley Research Center, Hampton, Virginia. The DAST Program merged advances in electronic remote control systems with advances in airplane design. Drones (remotely controlled, missile-like vehicles initially developed to serve as gunnery targets) had been deployed successfully during the Vietnamese conflict as reconnaissance aircraft. After the war, the energy crisis of the 1970s led NASA to seek new ways to cut fuel use and improve airplane efficiency. The DAST Program's drones provided an economical, fuel-conscious method for conducting in-flight experiments from a remote ground site. DAST explored the technology required to build wing structures with less than

  12. DAST in Flight Showing Diverging Wingtip Oscillations

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Two BQM-34 Firebee II drones were modified with supercritical airfoils, called the Aeroelastic Research Wing (ARW), for the Drones for Aerodynamic and Structural Testing (DAST) program, which ran from 1977 to 1983. In this view of DAST-1 (Serial # 72-1557), taken on June 12, 1980, severe wingtip flutter is visible. Moments later, the right wing failed catastrophically and the vehicle crashed near Cuddeback Dry Lake. Before the drone was lost, it had made two captive and two free flights. Its first free flight, on October 2, 1979, was cut short by an uplink receiver failure. The drone was caught in midair by an HH-3 helicopter. The second free flight, on March 12, 1980, was successful, ending in a midair recovery. The third free flight, made on June 12, was to expand the flutter envelope. All of these missions launched from the NASA B-52. From 1977 to 1983, the Dryden Flight Research Center, Edwards, California, (under two different names) conducted the DAST Program as a high-risk flight experiment using a ground-controlled, pilotless aircraft. Described by NASA engineers as a 'wind tunnel in the sky,' the DAST was a specially modified Teledyne-Ryan BQM-34E/F Firebee II supersonic target drone that was flown to validate theoretical predictions under actual flight conditions in a joint project with the Langley Research Center, Hampton, Virginia. The DAST Program merged advances in electronic remote control systems with advances in airplane design. Drones (remotely controlled, missile-like vehicles initially developed to serve as gunnery targets) had been deployed successfully during the Vietnamese conflict as reconnaissance aircraft. After the war, the energy crisis of the 1970s led NASA to seek new ways to cut fuel use and improve airplane efficiency. The DAST Program's drones provided an economical, fuel-conscious method for conducting in-flight experiments from a remote ground site. DAST explored the technology required to build wing structures with less than

  13. Surface-induced assembly of apolipoprotein A-I: Implications for symmetry-driven non-cooperative clustering

    NASA Astrophysics Data System (ADS)

    Winford, Sidney; Tobin, Moriah; Gross, Eitan

    2012-03-01

    In condensed matter physics the geometry of a crystal is determined by the mechanism of condensation. In biology, the link between clustering mechanisms and the shape of a protein crystal is not well defined. To gain more insight into the problem, we studied clustering of apolipoprotein A-I (apo A-I) on a solid surface using AFM. The amyloidogenic protein apo A-I is the main protein component of high density lipoprotein and thus reduces the risk of atherosclerosis. We found that apo A-I clustered to form nano-scale, symmetrical clusters on mica. Statistical analysis of size distribution for several thousand clusters suggested that the clustering reaction followed a non-cooperative kinetic scheme characterized by a single equilibrium constant of 0.92·106 M-1 and a change in free energy (ΔG) of -0.03 kJ mole-1/residue. This is close to ΔG of-0.04 kJ mole-1/residue for apo A-I binding to phospholipid membrane; and 30-fold smaller than ΔG for β-amyloid formation by apo A-I. The high symmetry of the clusters is consistent with an isotropic diffusion coefficient of protein monomers on the surface of the substrate. This previously unrecognized link between protein clustering mechanism and the symmetry of the growth pattern may have important implications in medicine, pharmaceutics and polymer science.

  14. 54. View from ground level in building no. 105 showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    54. View from ground level in building no. 105 showing lower radar scanner switch at open port door. Note incoming waveguide and control switch at lower left of photograph and note several waveguides leaving top of scanner switch around the circumference of switch. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

  15. Quantification of serum apolipoproteins A-I and B-100 in clinical samples using an automated SISCAPA-MALDI-TOF-MS workflow.

    PubMed

    van den Broek, Irene; Nouta, Jan; Razavi, Morteza; Yip, Richard; Bladergroen, Marco R; Romijn, Fred P H T M; Smit, Nico P M; Drews, Oliver; Paape, Rainer; Suckau, Detlev; Deelder, André M; van der Burgt, Yuri E M; Pearson, Terry W; Anderson, N Leigh; Cobbaert, Christa M

    2015-06-15

    A fully automated workflow was developed and validated for simultaneous quantification of the cardiovascular disease risk markers apolipoproteins A-I (apoA-I) and B-100 (apoB-100) in clinical sera. By coupling of stable-isotope standards and capture by anti-peptide antibodies (SISCAPA) for enrichment of proteotypic peptides from serum digests to matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS detection, the standardized platform enabled rapid, liquid chromatography-free quantification at a relatively high throughput of 96 samples in 12h. The average imprecision in normo- and triglyceridemic serum pools was 3.8% for apoA-I and 4.2% for apoB-100 (4 replicates over 5 days). If stored properly, the MALDI target containing enriched apoA-1 and apoB-100 peptides could be re-analyzed without any effect on bias or imprecision for at least 7 days after initial analysis. Validation of the workflow revealed excellent linearity for daily calibration with external, serum-based calibrators (R(2) of 0.984 for apoA-I and 0.976 for apoB-100 as average over five days), and absence of matrix effects or interference from triglycerides, protein content, hemolysates, or bilirubins. Quantification of apoA-I in 93 normo- and hypertriglyceridemic clinical sera showed good agreement with immunoturbidimetric analysis (slope = 1.01, R(2) = 0.95, mean bias = 4.0%). Measurement of apoB-100 in the same clinical sera using both methods, however, revealed several outliers in SISCAPA-MALDI-TOF-MS measurements, possibly as a result of the lower MALDI-TOF-MS signal intensity (slope = 1.09, R(2) = 0.91, mean bias = 2.0%). The combination of analytical performance, rapid cycle time and automation potential validate the SISCAPA-MALDI-TOF-MS platform as a valuable approach for standardized and high-throughput quantification of apoA-I and apoB-100 in large sample cohorts. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. AD-1 multiple exposure showing wing sweep

    NASA Technical Reports Server (NTRS)

    1980-01-01

    This photograph is a multiple exposure showing the AD-1 aircraft with its wing swept at different angles between zero and 60 degrees. The Ames-Dryden-1 (AD-1) aircraft was designed to investigate the concept of an oblique (pivoting) wing. The wing could be rotated on its center pivot, so that it could be set at its most efficient angle for the speed at which the aircraft was flying. NASA Ames Research Center Aeronautical Engineer Robert T. Jones conceived the idea of an oblique wing. His wind tunnel studies at Ames (Moffett Field, CA) indicated that an oblique wing design on a supersonic transport might achieve twice the fuel economy of an aircraft with conventional wings. The oblique wing on the AD-1 pivoted about the fuselage, remaining perpendicular to it during slow flight and rotating to angles of up to 60 degrees as aircraft speed increased. Analytical and wind tunnel studiesthat Jones conducted at Ames indicated that a transport-sized oblique-wing aircraft flying at speeds of up to Mach 1.4 (1.4 times the speed of sound) would have substantially better aerodynamic performance than aircraft with conventional wings. The AD-1 structure allowed the project to complete all of its technical objectives. The type of low-speed, low-cost vehicle - as expected - exhibited aeroelastic and pitch-roll-coupling effects that contributed to poor handling at sweep angles above 45 degrees. The fiberglass structure limited the wing stiffness that would have improved the handling qualities. Thus, after completion of the AD-1 project, there was still a need for a transonic oblique-wing research aircraft to assess the effects of compressibility, evaluate a more representative structure, and analyze flight performance at transonic speeds (those on either side of the speed of sound). The aircraft was delivered to the Dryden Flight Research Center, Edwards, CA, in March 1979 and its first flight was on December 21, 1979. Piloting the aircraft on that flight, as well as on its last

  17. AD-1 multiple exposure showing wing sweep

    NASA Technical Reports Server (NTRS)

    1980-01-01

    This photograph is a multiple exposure showing the AD-1 aircraft with its wing swept at different angles between zero and 60 degrees. The Ames-Dryden-1 (AD-1) aircraft was designed to investigate the concept of an oblique (pivoting) wing. The wing could be rotated on its center pivot, so that it could be set at its most efficient angle for the speed at which the aircraft was flying. NASA Ames Research Center Aeronautical Engineer Robert T. Jones conceived the idea of an oblique wing. His wind tunnel studies at Ames (Moffett Field, CA) indicated that an oblique wing design on a supersonic transport might achieve twice the fuel economy of an aircraft with conventional wings. The oblique wing on the AD-1 pivoted about the fuselage, remaining perpendicular to it during slow flight and rotating to angles of up to 60 degrees as aircraft speed increased. Analytical and wind tunnel studiesthat Jones conducted at Ames indicated that a transport-sized oblique-wing aircraft flying at speeds of up to Mach 1.4 (1.4 times the speed of sound) would have substantially better aerodynamic performance than aircraft with conventional wings. The AD-1 structure allowed the project to complete all of its technical objectives. The type of low-speed, low-cost vehicle - as expected - exhibited aeroelastic and pitch-roll-coupling effects that contributed to poor handling at sweep angles above 45 degrees. The fiberglass structure limited the wing stiffness that would have improved the handling qualities. Thus, after completion of the AD-1 project, there was still a need for a transonic oblique-wing research aircraft to assess the effects of compressibility, evaluate a more representative structure, and analyze flight performance at transonic speeds (those on either side of the speed of sound). The aircraft was delivered to the Dryden Flight Research Center, Edwards, CA, in March 1979 and its first flight was on December 21, 1979. Piloting the aircraft on that flight, as well as on its last

  18. Medicine's moment of misrule: the medical student show.

    PubMed

    Hayter, Charles R R

    2006-01-01

    Medical student shows are a prominent feature of medical student life around the world. Following a traditional vaudeville format of skits and songs, the shows are notorious for their exuberance, bawdiness, and lack of political correctness. Despite their widespread prevalence and sometimes hostile reactions, there has been no previous study of these shows. Based on research of scripts, programs, reviews, and oral history, this article explores their history and content and argues that, far from being irrelevant frivolities, these shows serve several important functions. These include the fostering of communal spirit, the development of skills in teamwork, and the collective ventilation of emotional reactions to the process of becoming a doctor. They are one offshoot of the ancient and important tradition of misrule in Western society.

  19. Mercury's Core Molten, Radar Study Shows

    NASA Astrophysics Data System (ADS)

    2007-05-01

    100 times, and showed that Mercury's spin axis is almost, but not exactly, perpendicular to the plane of its rotation around the Sun," Margot said. Margot worked with Stanton Peale of the University of California, Santa Barbara, Raymond Jurgens and Martin Slade of NASA's Jet Propulsion Laboratory, and Igor Holin of the Space Research Institute in Moscow. The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under cooperative agreement by Associated Universities, Inc. The Arecibo Observatory is part of the National Astronomy and Ionosphere Center, which is operated by Cornell University under a cooperative agreement with the NSF. Part of this work was supported by the Jet Propulsion Laboratory, operated by Caltech under contract with NASA.

  20. Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease.

    PubMed

    Yao, Xianglan; Gordon, Elizabeth M; Figueroa, Debbie M; Barochia, Amisha V; Levine, Stewart J

    2016-08-01

    Emerging roles are being recognized increasingly for apolipoproteins in the pathogenesis and treatment of lung diseases on the basis of their ability to suppress inflammation, oxidative stress, and tissue remodeling, and to promote adaptive immunity and host defense. Apolipoproteins, such as apolipoprotein E (apoE) and apolipoprotein A-I (apoA-I), are important components of lipoprotein particles that facilitate the transport of cholesterol, triglycerides, and phospholipids between plasma and cells. ApoE-containing lipoprotein particles are internalized into cells by low-density lipoprotein receptors (LDLRs), whereas apoA-I can interact with the ATP-binding cassette subfamily A member 1 (ABCA1) transporter to efflux cholesterol and phospholipids out of cells. ApoE and apoA-I also mediate receptor-independent effects, such as binding to and neutralizing LPS. Both apoE and apoA-I are expressed by lung cells, which allows apoE/LDLR- and apoA-I/ABCA1-dependent pathways to modulate normal lung health and the pathogenesis of respiratory diseases, including asthma, acute lung injury, cancer, emphysema, pulmonary fibrosis, and pulmonary hypertension. Data from human studies and research using experimental murine model systems have shown that both apoE and apoA-I pathways play primarily protective roles in lung biology and respiratory disease. Furthermore, apolipoprotein mimetic peptides, corresponding to the LDLR-binding domain of apoE or the class A amphipathic α-helical structure of apoA-I, have antiinflammatory and antioxidant effects that attenuate the severity of lung disease in murine models. Thus, the development of inhaled apolipoprotein mimetic peptides as a novel treatment paradigm could represent a significant advance for patients with respiratory disease who do not respond to current therapies.

  1. Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease

    PubMed Central

    Yao, Xianglan; Gordon, Elizabeth M.; Figueroa, Debbie M.; Barochia, Amisha V.

    2016-01-01

    Emerging roles are being recognized increasingly for apolipoproteins in the pathogenesis and treatment of lung diseases on the basis of their ability to suppress inflammation, oxidative stress, and tissue remodeling, and to promote adaptive immunity and host defense. Apolipoproteins, such as apolipoprotein E (apoE) and apolipoprotein A-I (apoA-I), are important components of lipoprotein particles that facilitate the transport of cholesterol, triglycerides, and phospholipids between plasma and cells. ApoE-containing lipoprotein particles are internalized into cells by low-density lipoprotein receptors (LDLRs), whereas apoA-I can interact with the ATP-binding cassette subfamily A member 1 (ABCA1) transporter to efflux cholesterol and phospholipids out of cells. ApoE and apoA-I also mediate receptor-independent effects, such as binding to and neutralizing LPS. Both apoE and apoA-I are expressed by lung cells, which allows apoE/LDLR- and apoA-I/ABCA1-dependent pathways to modulate normal lung health and the pathogenesis of respiratory diseases, including asthma, acute lung injury, cancer, emphysema, pulmonary fibrosis, and pulmonary hypertension. Data from human studies and research using experimental murine model systems have shown that both apoE and apoA-I pathways play primarily protective roles in lung biology and respiratory disease. Furthermore, apolipoprotein mimetic peptides, corresponding to the LDLR-binding domain of apoE or the class A amphipathic α-helical structure of apoA-I, have antiinflammatory and antioxidant effects that attenuate the severity of lung disease in murine models. Thus, the development of inhaled apolipoprotein mimetic peptides as a novel treatment paradigm could represent a significant advance for patients with respiratory disease who do not respond to current therapies. PMID:27073971

  2. Predicting eczema severity beyond childhood.

    PubMed

    Hon, Kam Lun; Tsang, Yin-Ching K; Poon, Terence Chuen W; Pong, Nga Hin; Kwan, Matthew; Lau, Shirley; Chiu, Yuen-Chun; Wong, Hin-Hei; Leung, Ting-Fan

    2016-02-01

    We evaluated factors associated with eczema severity in adolescence. Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test for common food and aeroallergens, highest serum IgE level and eosinophil count were evaluated. Patients with paired NESSs (childhood-NESS is NESS performed at <10 years of age; adolescence-NESS is NESS performed at age >10 years) were further analyzed. Adolescence-NESS (n=383 patients) was associated with eczema onset in infancy, dust mite and food allergen sensitization, dietary avoidance, use of wet wrap, traditional Chinese medicine, immunomodulant (azathioprine or cyclosporine), high IgE level, eosinophil count, but not with family/personal history of atopy. Eighty-two patients had both childhood-NESS and adolescence-NESS (mean follow-up of 6.8 years) showing that adolescence-NESS was associated with childhood- NESS severity grades (P=0.034). Of these patients, 48% remained in the same severity grades, whereas 39% improved, and 13% deteriorated from childhood to adolescence. It is not possible to assure parents that their child can outgrow eczema. In eczema prognosis research, long-term follow-up is warranted.

  3. [Severe edematous dermatomyositis].

    PubMed

    Goussot, R; Wettlé, C; Le Coz, C; Cribier, B; Lipsker, D

    2016-03-01

    Edematous dermatomyositis is a rare entity with localized or generalized subcutaneous edema and only 21 cases have been reported in the literature. It is considered to be a severe form of dermatomyositis which needs quick therapeutic decision. We report 2 cases with difficult therapeutic decisions. Two patients aged 23 and 80 years were admitted in hospital for DM with typical cutaneous and muscular involvement without any sign of gravity and which have been treated by steroids: methylprednisolone bolus and prednisone. They both then developed severe edema of the upper limbs as well as worsening of the cutaneous and muscular symptoms with dysphagia. The addition of mycophenolate mofetil and intravenous immunoglobulin has permitted in the case of the first patient the disappearance of the cutaneous symptoms in particular the edema with restitution of the muscular force and withdrawal of the dysphagia and swallowing symptoms. The therapeutic failure for the second patient was due to a refusal of the treatment and a probable paraneoplastic context. Subcutaneous edema localized or generalized must not be confused with periorbital erythematous edema, classically observed in DM, nor with DM with mucinosis. Potential marker of gravity, it is often associated to important muscular weakness and dysphagia. In this case, an aggressive treatment associating corticosteroids, immunosuppressive therapy and intravenous immunoglobulin is necessary. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Structures of apolipoprotein A-I in high density lipoprotein generated by electron microscopy and biased simulations.

    PubMed

    Zhu, Lin; Petrlova, Jitka; Gysbers, Peter; Hebert, Hans; Wallin, Stefan; Jegerschöld, Caroline; Lagerstedt, Jens O

    2017-07-25

    Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) is a key protein for the transport of cholesterol from the vascular wall to the liver. The formation and structure of nascent HDL, composed of apoA-I and phospholipids, is critical to this process. The HDL was assembled in vitro from apoA-I, cholesterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at a 1:4:50 molar ratio. The structure of HDL was investigated in vitreous samples, frozen at cryogenic temperatures, as well as in negatively stained samples by transmission electron microscopy. Low resolution electron density maps were next used as restraints in biased Monte Carlo simulations of apolipoprotein A-I dimers, with an initial structure derived from atomic resolution X-ray structures. Two final apoA-I structure models for the full-length structure of apoA-I dimer in the lipid bound conformation were generated, showing a nearly circular, flat particle with an uneven particle thickness. The generated structures provide evidence for the discoidal, antiparallel arrangement of apoA-I in nascent HDL, and propose two preferred conformations of the flexible N-termini. The novel full-length structures of apoA-I dimers deepens the understanding to the structure-function relationship of nascent HDL with significance for the prevention of lipoprotein-related disease. The biased simulation method used in this study provides a powerful and convenient modelling tool with applicability for structural studies and modelling of other proteins and protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis.

    PubMed

    Garber, Caren; Plotnikova, Natalia; Au, Shiu-chung; Sorensen, Eric P; Gottlieb, Alice

    2015-08-01

    Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly safe and effective in the elderly and non-elderly cohorts. Within the elderly population, biologics may be a safer option than conventional systemic agents.

  6. A cellular study of teosinte Zea mays ssp. parviglumis (Poaceae) caryopsis development showing several processes conserved in maize

    USDA-ARS?s Scientific Manuscript database

    Although recent molecular studies elucidate the genetic background leading to changed morphology of maize female inflorescence and the structure of the caryopsis during the domestication of maize (Zea mays ssp. mays) from its wild progenitor teosinte (Zea mays ssp. parviglumis), the mechanisms under...

  7. LEAD SEVERING CONTRIVANCE

    DOEpatents

    Widmaier, W.

    1958-04-01

    A means for breaking an electrical circuit within an electronic tube during the process of manufacture is described. Frequently such circuits must be employed for gettering or vapor coating purposes, however, since an external pair of corector pins having no use after manufacture, is undesirable, this invention permits the use of existing leads to form a temporary circuit during manufacture, and severing it thereafter. One portion of the temporary circuit, made from a springy material such as tungsten, is spot welded to a fusable member. To cut the circuit an external radiant heat source melts the fusable member, allowing the tensed tungsten spring to contract and break the circuit. This inexpensive arrangement is particularly useful when the tube has a great many external leads crowded into the tube base.

  8. Severe storm electricity

    NASA Technical Reports Server (NTRS)

    Arnold, R. T.; Rust, W. D.

    1984-01-01

    Successful ground truth support of U-2 overflights was been accomplished. Data have been reduced for 4 June 1984 and some of the results have been integrated into some of MSFC's efforts. Staccato lightning (multiply branched, single stroke flash with no continuing current) is prevalent within the rainfree region around the main storm updraft and this is believed to be important, i.e., staccato flashes might be an important indicator of severe storm electrification. Results from data analysis from two stations appear to indicate that charge center heights can be estimated from a combination of intercept data with data from the fixed laboratory at NSSL. An excellent data base has been provided for determining the sight errors and efficiency of NSSL's LLP system. Cloud structures, observable in a low radar reflectivity region and on a scale smaller than is currently resolved by radar, which appear to be related to electrical activity are studied.

  9. Measurement by phase severance

    SciTech Connect

    Noyes, H.P.

    1987-03-01

    It is claimed that the measurement process is more accurately described by ''quasi-local phase severance'' than by ''wave function collapse''. The approach starts from the observation that the usual route to quantum mechanics starting from the Hamilton-Jacobi equations throws away half the degrees of freedom, namely, the classical initial state parameters. To overcome this difficulty, the full set of Hamilton-Jacobi equations is interpreted as operator equations acting on a state vector. The measurement theory presented is based on the conventional S-matrix boundary condition of N/sub A/ free particles in the distant past and N/sub B/ free particles in the distant future and taking the usual free particle wave functions, multiplied by phase factors.

  10. Terlipressin Induced Severe Hyponatremia.

    PubMed

    Šíma, Martin; Pokorný, Miroslav; Paďour, František; Slanař, Ondřej

    2016-01-01

    Terlipressin is a vasopressin analogue used for its vasoconstrictor effect in the treatment of variceal bleeding. Despite its good safety profile compared to vasopressin, some adverse reactions may occur during its use - e.g. hyponatremia. We describe a case of a cirrhotic patient with active variceal bleeding treated during two separate hospitalizations with terlipressin. In both drug treatment periods, severe laboratory hyponatremia developed. After terlipressin discontinuation, mineral disbalance corrected rapidly. Positive dechallenge and rechallenge corresponding to the drug administration schedule confirms the causality between terlipressin administration and hyponatremia. Hyponatremia was preceded with substantial fluid retention in both episodes. In this case report we want to highlight the need for fluid balance monitoring immediately after first terlipressin dose, which may individually predict the patient risk for the development of hyponatremia as other risk factors have rather limited predictive value in real clinical settings.

  11. Nutrition in Severe Dementia

    PubMed Central

    Pivi, Glaucia Akiko Kamikado; Bertolucci, Paulo Henrique Ferreira; Schultz, Rodrigo Rizek

    2012-01-01

    An increasing proportion of older adults with Alzheimer's disease or other dementias are now surviving to more advanced stages of the illness. Advanced dementia is associated with feeding problems, including difficulty in swallowing and respiratory diseases. Patients become incompetent to make decisions. As a result, complex situations may arise in which physicians and families decide whether artificial nutrition and hydration (ANH) is likely to be beneficial for the patient. The objective of this paper is to present methods for evaluating the nutritional status of patients with severe dementia as well as measures for the treatment of nutritional disorders, the use of vitamin and mineral supplementation, and indications for ANH and pharmacological therapy. PMID:22645608

  12. Decreased apolipoprotein A-I level indicates poor prognosis in extranodal natural killer/T-cell lymphoma, nasal type

    PubMed Central

    Quan, Qi; Chen, Qi; Chen, Ping; Jiang, Li; Li, Tingwei; Qiu, Huijuan; Zhang, Bei

    2016-01-01

    Background Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an invasive lymphoid malignancy with unfavorable survival, for which a prognostic model has not yet been validated. We hypothesized that serum apolipoprotein A-I (ApoA-I) may serve as a novel prognostic marker for ENKTL. Patients and methods A total of 236 newly diagnosed cases of ENKTL were analyzed retrospectively. Results The optimal cutoff value for the serum ApoA-I level was determined to be 0.95 g/L. A total of 154 and 82 cases were assigned to the high and low ApoA-I groups, respectively. Patients in the low ApoA-I group tended to present with poorer clinical features, a lower complete remission rate (P=0.001), and poor median progression-free survival (P<0.001) and overall survival (P<0.001). Multivariate analysis using Cox model showed that the serum ApoA-I level was an independent prognostic marker of overall survival (P<0.001) and progression-free survival (P<0.001) for ENKTL patients. For cases in the low-risk group, as assessed by International Prognostic Index, Prognosis Index for peripheral T-cell lymphoma, unspecified, and Korean Prognostic Index, the serum ApoA-I level was able to differentiate cases with poor outcomes from cases with good outcomes. Conclusion Our results showed that the baseline serum ApoA-I level was helpful for predicting ENKTL prognosis. PMID:27051293

  13. Lipid-Free Apolipoprotein A-I Reduces Progression of Atherosclerosis by Mobilizing Microdomain Cholesterol and Attenuating the Number of CD131 Expressing Cells: Monitoring Cholesterol Homeostasis Using the Cellular Ester to Total Cholesterol Ratio.

    PubMed

    Kaul, Sushma; Xu, Hao; Zabalawi, Manal; Maruko, Elisa; Fulp, Brian E; Bluemn, Theresa; Brzoza-Lewis, Kristina L; Gerelus, Mark; Weerasekera, Ranjuna; Kallinger, Rachel; James, Roland; Zhang, Yi Sherry; Thomas, Michael J; Sorci-Thomas, Mary G

    2016-11-07

    Atherosclerosis is a chronic inflammatory disorder whose development is inversely correlated with high-density lipoprotein concentration. Current therapies involve pharmaceuticals that significantly elevate plasma high-density lipoprotein cholesterol concentrations. Our studies were conducted to investigate the effects of low-dose lipid-free apolipoprotein A-I (apoA-I) on chronic inflammation. The aims of these studies were to determine how subcutaneously injected lipid-free apoA-I reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without sustained elevations in plasma high-density lipoprotein cholesterol concentrations. Ldlr(-/-) and Ldlr(-/-) apoA-I(-/-) mice were fed a Western diet for a total of 12 weeks. After 6 weeks, a subset of mice from each group received subcutaneous injections of 200 μg of lipid-free human apoA-I 3 times a week, while the other subset received 200 μg of albumin, as a control. Mice treated with lipid-free apoA-I showed a decrease in cholesterol deposition and immune cell retention in the aortic root compared with albumin-treated mice, regardless of genotype. This reduction in atherosclerosis appeared to be directly related to a decrease in the number of CD131 expressing cells and the esterified cholesterol to total cholesterol content in several immune cell compartments. In addition, apoA-I treatment altered microdomain cholesterol composition that shifted CD131, the common β subunit of the interleukin 3 receptor, from lipid raft to nonraft fractions of the plasma membrane. ApoA-I treatment reduced lipid and immune cell accumulation within the aortic root by systemically reducing microdomain cholesterol content in immune cells. These data suggest that lipid-free apoA-I mediates beneficial effects through attenuation of immune cell lipid raft cholesterol content, which affects numerous types of signal transduction pathways that rely on microdomain integrity for assembly and

  14. Site-specific Nitration of Apolipoprotein A-I at Tyrosine 166 Is Both Abundant within Human Atherosclerotic Plaque and Dysfunctional*

    PubMed Central

    DiDonato, Joseph A.; Aulak, Kulwant; Huang, Ying; Wagner, Matthew; Gerstenecker, Gary; Topbas, Celalettin; Gogonea, Valentin; DiDonato, Anthony J.; Tang, W. H. Wilson; Mehl, Ryan A.; Fox, Paul L.; Plow, Edward F.; Smith, Jonathan D.; Fisher, Edward A.; Hazen, Stanley L.

    2014-01-01

    We reported previously that apolipoprotein A-I (apoA-I) is oxidatively modified in the artery wall at tyrosine 166 (Tyr166), serving as a preferred site for post-translational modification through nitration. Recent studies, however, question the extent and functional importance of apoA-I Tyr166 nitration based upon studies of HDL-like particles recovered from atherosclerotic lesions. We developed a monoclonal antibody (mAb 4G11.2) that recognizes, in both free and HDL-bound forms, apoA-I harboring a 3-nitrotyrosine at position 166 apoA-I (NO2-Tyr166-apoA-I) to investigate the presence, distribution, and function of this modified apoA-I form in atherosclerotic and normal artery wall. We also developed recombinant apoA-I with site-specific 3-nitrotyrosine incorporation only at position 166 using an evolved orthogonal nitro-Tyr-aminoacyl-tRNA synthetase/tRNACUA pair for functional studies. Studies with mAb 4G11.2 showed that NO2-Tyr166-apoA-I was easily detected in atherosclerotic human coronary arteries and accounted for ∼8% of total apoA-I within the artery wall but was nearly undetectable (>100-fold less) in normal coronary arteries. Buoyant density ultracentrifugation analyses showed that NO2-Tyr166-apoA-I existed as a lipid-poor lipoprotein with <3% recovered within the HDL-like fraction (d = 1.063–1.21). NO2-Tyr166-apoA-I in plasma showed a similar distribution. Recovery of NO2-Tyr166-apoA-I using immobilized mAb 4G11.2 showed an apoA-I form with 88.1 ± 8.5% reduction in lecithin-cholesterol acyltransferase activity, a finding corroborated using a recombinant apoA-I specifically designed to include the unnatural amino acid exclusively at position 166. Thus, site-specific nitration of apoA-I at Tyr166 is an abundant modification within the artery wall that results in selective functional impairments. Plasma levels of this modified apoA-I form may provide insights into a pathophysiological process within the diseased artery wall. PMID:24558038

  15. Influence of C-terminal α-helix hydrophobicity and aromatic amino acid content on apolipoprotein A-I functionality.

    PubMed

    Lyssenko, Nicholas N; Hata, Mami; Dhanasekaran, Padmaja; Nickel, Margaret; Nguyen, David; Chetty, Palaniappan Sevugan; Saito, Hiroyuki; Lund-Katz, Sissel; Phillips, Michael C

    2012-03-01

    The apoA-I molecule adopts a two-domain tertiary structure and the properties of these domains modulate the ability to form HDL particles. Thus, human apoA-I differs from mouse apoA-I in that it can form smaller HDL particles; the C-terminal α-helix is important in this process and human apoA-I is unusual in containing aromatic amino acids in the non-polar face of this amphipathic α-helix. To understand the influence of these aromatic amino acids and the associated high hydrophobicity, apoA-I variants were engineered in which aliphatic amino acids were substituted with or without causing a decrease in overall hydrophobicity. The variants human apoA-I (F225L/F229A/Y236A) and apoA-I (F225L/F229L/A232L/Y236L) were compared to wild-type (WT) apoA-I for their abilities to (1) solubilize phospholipid vesicles and form HDL particles of different sizes, and (2) mediate cellular cholesterol efflux and create nascent HDL particles via ABCA1. The loss of aromatic residues and concomitant decrease in hydrophobicity in apoA-I (F225L/F229A/Y236A) has no effect on protein stability, but reduces by a factor of about three the catalytic efficiencies (V(max)/K(m)) of vesicle solubilization and cholesterol efflux; also, relatively large HDL particles are formed. With apoA-I (F225L/F229L/A232L/Y236L) where the hydrophobicity is restored by the presence of only leucine residues in the helix non-polar face, the catalytic efficiencies of vesicle solubilization and cholesterol efflux are similar to those of WT apoA-I; this variant forms smaller HDL particles. Overall, the results show that the hydrophobicity of the non-polar face of the C-terminal amphipathic α-helix plays a critical role in determining apoA-I functionality but aromatic amino acids are not required. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Folded functional lipid-poor apolipoprotein A-I obtained by heating of high-density lipoproteins: relevance to high-density lipoprotein biogenesis.

    PubMed

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-03-15

    HDL (high-density lipoproteins) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apoA-I (apolipoprotein A-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL to produce lipid-poor apoA-I. Analysis of the isolated lipid-poor fraction showed a protein/lipid weight ratio of 3:1, with apoA-I, PC (phosphatidylcholine) and CE (cholesterol ester) at approximate molar ratios of 1:8:1. Compared with lipid-free apoA-I, lipid-poor apoA-I showed slightly altered secondary structure and aromatic packing, reduced thermodynamic stability, lower self-associating propensity, increased adsorption to phospholipid surface and comparable ability to remodel phospholipids and form reconstituted HDL. Lipid-poor apoA-I can be formed by heating of either plasma or reconstituted HDL. We propose the first structural model of lipid-poor apoA-I which corroborates its distinct biophysical properties and postulates the lipid-induced ordering of the labile C-terminal region. In summary, HDL heating produces folded functional monomolecular lipid-poor apoA-I that is distinct from lipid-free apoA-I. Increased adsorption to phospholipid surface and reduced C-terminal disorder may help direct lipid-poor apoA-I towards HDL biogenesis.

  17. The Impact of Plant Enemies Shows a Phylogenetic Signal

    PubMed Central

    Gilbert, Gregory S.; Briggs, Heather M.; Magarey, Roger

    2015-01-01

    The host ranges of plant pathogens and herbivores are phylogenetically constrained, so that closely related plant species are more likely to share pests and pathogens. Here we conducted a reanalysis of data from published experimental studies to test whether the severity of host-enemy interactions follows a similar phylogenetic signal. The impact of herbivores and pathogens on their host plants declined steadily with phylogenetic distance from the most severely affected focal hosts. The steepness of this phylogenetic signal was similar to that previously measured for binary-response host ranges. Enemy behavior and development showed similar, but weaker phylogenetic signal, with oviposition and growth rates declining with evolutionary distance from optimal hosts. Phylogenetic distance is an informative surrogate for estimating the likely impacts of a pest or pathogen on potential plant hosts, and may be particularly useful in early assessing risk from emergent plant pests, where critical decisions must be made with incomplete host records. PMID:25893581

  18. Effect of amino acid distribution of amphipathic helical peptide derived from human apolipoprotein A-I on membrane curvature sensing.

    PubMed

    Tanaka, Masafumi; Takamura, Yuki; Kawakami, Toru; Aimoto, Saburo; Saito, Hiroyuki; Mukai, Takahiro

    2013-03-01

    Amphipathic helix, which senses membrane curvature, is of growing interest. Here we explore the effect of amino acid distribution of amphipathic helical peptide derived from the C-terminal region (residues 220-241) of human apolipoprotein (apo) A-I on membrane curvature sensing. This peptide preferred a curved membrane in a manner similar to full-length apoA-I, although its model peptide did not sense membrane curvature. Substitution of several residues both on the polar and non-polar faces of the amphipathic helix had no significant effect on sensing, suggestive of the elaborate molecular architecture in the C-terminal helical region of apoA-I to exert lipid efflux function. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Severe storm electricity

    NASA Technical Reports Server (NTRS)

    Rust, W. D.; Macgorman, D. R.; Taylor, W.; Arnold, R. T.

    1984-01-01

    Severe storms and lightning were measured with a NASA U2 and ground based facilities, both fixed base and mobile. Aspects of this program are reported. The following results are presented: (1) ground truth measurements of lightning for comparison with those obtained by the U2. These measurements include flash type identification, electric field changes, optical waveforms, and ground strike location; (2) simultaneous extremely low frequency (ELF) waveforms for cloud to ground (CG) flashes; (3) the CG strike location system (LLP) using a combination of mobile laboratory and television video data are assessed; (4) continued development of analog-to-digital conversion techniques for processing lightning data from the U2, mobile laboratory, and NSSL sensors; (5) completion of an all azimuth TV system for CG ground truth; (6) a preliminary analysis of both IC and CG lightning in a mesocyclone; and (7) the finding of a bimodal peak in altitude lightning activity in some storms in the Great Plains and on the east coast. In the forms on the Great Plains, there was a distinct class of flash what forms the upper mode of the distribution. These flashes are smaller horizontal extent, but occur more frequently than flashes in the lower mode of the distribution.

  20. Storm severity detection (RF)

    NASA Technical Reports Server (NTRS)

    Johnson, R. L.; Goodman, S. J.

    1985-01-01

    Atmospheric electrical emissions occurring in association with Hurricane Alicia were observed by two crossed baseline phase linear interferometers. The sensors were located in San Antonio, Texas, and at Marshall Space Flight Center (MSFC), Huntsville, Alabama. An analysis of the data has indicated that the direction finding (DF) performance of the San Antonio site was extremely good while the DF performance at the MSFC site evidenced erratic behavior. A check of the data acquisition hardware revealed an intermitted problem in one of the radio receiver channels. Since the system has experienced several lightning strikes during the early spring of 1984, it was necessary to ship the entire rack of equipment back to SwRI for refurbishment. Analysis of the DF data from the interferometer site at San Antonio is being done. A limited subset of the MSFC data acquired during Hurricane Alicia has been found to be valid. These were data which satisfied the phase linearity criteria. Approximately 2,000 location estimates have been produced on the valid data. The results of the DF analysis and the location data are being correlated with the McIDAS data base at Marshall Space Flight Center, and with the radar summary data provided by the Hurricane Research Division using the National weather Service radar Facility at Galveston, Texas.

  1. Severe Exoplanetary Storm

    NASA Technical Reports Server (NTRS)

    2009-01-01

    These computer-generated images chart the development of severe weather patterns on the highly eccentric exoplanet HD 80606b during the days after its closest approach to its parent star. An exoplanet is a planet that orbits a star other than our sun.

    The images were produced by computer simulations that modeled NASA's Spitzer Space Telescope's measurements of heat radiating from the planet. The six frames are evenly spaced in time, starting from 4.4 days after the planet's close approach to the star, a moment known as 'periastron,' and running through 8.9 days after periastron. The blue glow of the crescent is starlight that has been scattered and reflected by the planet. The starlight appears blue because the planet is a very efficient absorber of red light. The night side appears reddish orange as it glows with its own internal heat.

    These theoretical models allow astronomers to better understand weather patterns on distant planets. While direct telescopic observations of the atmospheres of such worlds may be many decades away, such simulations give us a clue to what we may see when it becomes possible.

    The Spitzer observations themselves spanned the relatively brief period when the heating of the planet was most intense, running from 20 hours prior to 10 hours after periastron. The data were taken in Nov. of 2007.

    HD 80606b is located 190 light-years away in the constellation Ursa Major. Its star can be seen with binoculars.

  2. Storm severity detection (RF)

    NASA Technical Reports Server (NTRS)

    Johnson, R. L.; Goodman, S. J.

    1985-01-01

    Atmospheric electrical emissions occurring in association with Hurricane Alicia were observed by two crossed baseline phase linear interferometers. The sensors were located in San Antonio, Texas, and at Marshall Space Flight Center (MSFC), Huntsville, Alabama. An analysis of the data has indicated that the direction finding (DF) performance of the San Antonio site was extremely good while the DF performance at the MSFC site evidenced erratic behavior. A check of the data acquisition hardware revealed an intermitted problem in one of the radio receiver channels. Since the system has experienced several lightning strikes during the early spring of 1984, it was necessary to ship the entire rack of equipment back to SwRI for refurbishment. Analysis of the DF data from the interferometer site at San Antonio is being done. A limited subset of the MSFC data acquired during Hurricane Alicia has been found to be valid. These were data which satisfied the phase linearity criteria. Approximately 2,000 location estimates have been produced on the valid data. The results of the DF analysis and the location data are being correlated with the McIDAS data base at Marshall Space Flight Center, and with the radar summary data provided by the Hurricane Research Division using the National weather Service radar Facility at Galveston, Texas.

  3. Severe acute malnutrition.

    PubMed

    Nel, E D

    2016-05-01

    The mortality and morbidity associated with severe acute malnutrition (SAM) remain high. A summary of recent studies that are of interest to clinicians treating children with SAM is provided. Three important themes emerged in 2015: the use of anthropometry in the diagnosis of SAM and its correlation with body composition; the composition of ready-to-use therapeutic feeds (RUTF); and an improved understanding of the pathophysiology of SAM. Standard anthropometry does not accurately predict body composition and mid-upper arm circumference more accurately reflects fat mass in children. As single measure, mid-upper arm circumference identifies those children who are most likely to die from SAM and is not influenced by dehydration. However, a significant proportion of SAM children requiring treatment will not be detected. Present RUTF formulations are deficient in long chain polyunsaturated fatty acids. Current evidence suggests that preformed docosahexaenoic acid should be added and/or the content of linoleic acid reduced in RUTF. In contrast to an animal model, stabile children with SAM have the same cardiac index as children without SAM. The situation in haemodynamically unstable children is unknown, continued conservative use of intravenous fluids seems advisable. A reduction in variability of the faecal DNA virome may account for increased susceptibility to malnutrition in vulnerable children.

  4. Gender differences in addiction severity.

    PubMed

    Díaz-Mesa, Eva M; García-Portilla, Paz; Fernández-Artamendi, Sergio; Sáiz, Pilar A; Bobes Bascarán, Teresa; Casares, María José; Fonseca, Eduardo; Al-Halabí, Susana; Bobes, Julio

    2016-06-14

    Gender has been associated with substance use disorders (SUD). However, there are few studies that have evaluated gender differences in a global and a standardized way, and with a large sample of patients with SUD. Our goal is to analyze the role of gender in addiction severity throughout multiple life domains, using the Addiction Severity Index-6 (ASI-6). A naturalistic, multicenter and prospective study was conducted. A total of 221 patients with SUD (80.1% men) were interviewed with the ASI-6. Our results indicate that the Recent Summary Scores (RSSs) of men and women are similar, with the exception of Psychiatric and Partner- Problems, where women showed higher severity (p = .017 and p = .013, respectively). Statistically significant gender differences were found in certain aspects of the ASI-6 domains: men have more problems of physical health, legal issues, and alcohol and other substance use; and woman score higher in problems of mental health, social network, subjective evaluations of SUD consequences, and treatment needs. These results should be taken into account to improve the identification, prevention, and treatment of SUD.

  5. Ectasia and Severe Atherosclerosis

    PubMed Central

    Adiloglu, Ali K.; Can, Rabia; Nazli, Cem; Ocal, Ahmet; Ergene, Oktay; Tinaz, Gulgun; Kisioglu, Nesimi

    2005-01-01

    To date, there has been no convincing evidence for an association between Chlamydia pneumoniae or Helicobacter pylori and ectasia. In this case-control study, we have investigated the association of H. pylori and C. pneumoniae seropositivity with ectasia, severe coronary atherosclerosis, and normal vessels, which were so classified by coronary angiography. We have also evaluated the influence of these infections on inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6). Of the 796 patients undergoing coronary angiography for suspected ischemic heart disease, 244 patients were recruited. Of these, 91 had normal vessels, 88 had 3 or more obstructed vessels, and 65 had ectatic vessels without atherosclerosis. Eighty-seven atherosclerotic patients (98.9%) were positive for C. pneumoniae IgG, as were 64 ectatic patients (98.5%) and 76 controls (83.5%) (P < 0.001). Forty-two atherosclerotic patients (47.7%) were positive for C. pneumoniae IgM, as were 43 ectatic patients (66.2%) and 43 controls (47.3%) (P = 0.036). Seventy-two atherosclerotic patients (81.8%) were positive for H. pylori IgA, as were 26 ectatic patients (40.0%) and 44 controls (48.4%) (P < 0.001). High-sensitive CRP levels were significantly higher in ectatic patients (5.639 mg/L) than in controls (4.390 mg/L) (P = 0.032), and IL-6 levels were significantly higher in atherosclerotic patients (33.92 U/L) than in controls (14.01 U/L) (P < 0.001). Interleukin-6 levels were higher in H. pylori seropositive patients, and hsCRP levels were higher in C. pneumoniae seropositive patients, when compared with seronegatives. We suggest that, as in atherosclerosis, C. pneumoniae infection is related to ectasia, with raised CRP levels. PMID:15902817

  6. Closeup view of portion of swingspan truss showing members and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Close-up view of portion of swing-span truss showing members and their pin connections at joints. The vertical member (hanger) shown is a portion of a small secondary truss added in each subdivided panel to help support the bottom chord. The track timber ties span the distance (16'-0') center to center of trusses, rest on the bottom chord and support the track. Note: Several of the members shown are eyebars. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  7. 26. A typical outer rod room, or rack room, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. A typical outer rod room, or rack room, showing the racks for the nine horizontal control rods (HCRs) that would be inserted or withdrawn from the pile to control the rate of reaction. In this case, it is the 105-F Reactor in February 1945. The view is looking away from the pile, which is out of the picture on the left. Several of the cooling water hose reels for the rods can be seen at the end of the racks near the wall. D-8323 - B Reactor, Richland, Benton County, WA

  8. Elevated homocysteine reduces apolipoprotein A-I expression in hyperhomocysteinemic mice and in males with coronary artery disease.

    PubMed

    Mikael, Leonie G; Genest, Jacques; Rozen, Rima

    2006-03-03

    Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. A polymorphism in methylenetetrahydrofolate reductase (MTHFR) is the most common genetic cause of mild hyperhomocysteinemia. To examine mechanisms by which an elevation in plasma homocysteine leads to vascular disease, we first performed microarray analyses in livers of Mthfr-deficient mice and identified differentially expressed genes that are involved in lipid and cholesterol metabolism. Microarrays and RT-PCR showed decreased mRNA for apolipoprotein A (ApoA)-IV and for ApoA-I and increased mRNA for cholesterol 7alpha hydroxylase (Cyp7A1) in Mthfr(+/-) mice compared with Mthfr(+/+) mice. Western blotting revealed that ApoA-I protein levels in liver and plasma of Mthfr(+/-) mice were 52% and 62% of levels in the respective tissues of Mthfr(+/+) mice. We also performed Western analysis for plasma ApoA-I protein levels in 60 males with coronary artery disease and identified a significant (P<0.01) negative correlation (-0.33) between ApoA-I and plasma homocysteine levels. This cohort also displayed a negative correlation (-0.24, P=0.06) between high-density lipoprotein cholesterol and plasma homocysteine. Treatment of HepG2 cells with supraphysiological levels of 5 mmol/L homocysteine reduced peroxisome proliferator-activated receptor (PPAR) alpha and ApoA-I protein levels and decreased ApoA-I promoter activity. Transfection with a PPARalpha construct upregulated ApoA-I and MTHFR. Our results suggest that hyperhomocysteinemia may increase risk of atherosclerosis by decreasing expression of ApoA-I and increasing expression of CYP7A1.

  9. Apolipoprotein A-II-mediated Conformational Changes of Apolipoprotein A-I in Discoidal High Density Lipoproteins*

    PubMed Central

    Gauthamadasa, Kekulawalage; Vaitinadin, Nataraja Sarma; Dressman, James L.; Macha, Stephen; Homan, Reyn; Greis, Kenneth D.; Silva, R. A. Gangani D.

    2012-01-01

    It is well accepted that HDL has the ability to reduce risks for several chronic diseases. To gain insights into the functional properties of HDL, it is critical to understand the HDL structure in detail. To understand interactions between the two major apolipoproteins (apos), apoA-I and apoA-II in HDL, we generated highly defined benchmark discoidal HDL particles. These particles were reconstituted using a physiologically relevant phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) incorporating two molecules of apoA-I and one homodimer of apoA-II per particle. We utilized two independent mass spectrometry techniques to study these particles. The techniques are both sensitive to protein conformation and interactions and are namely: 1) hydrogen deuterium exchange combined with mass spectrometry and 2) partial acetylation of lysine residues combined with MS. Comparison of mixed particles with apoA-I only particles of similar diameter revealed that the changes in apoA-I conformation in the presence of apoA-II are confined to apoA-I helices 3–4 and 7–9. We discuss these findings with respect to the relative reactivity of these two particle types toward a major plasma enzyme, lecithin:cholesterol acyltransferase responsible for the HDL maturation process. PMID:22235130

  10. Radial-immunodiffusion assay of human apolipoprotein A-I with use of two monoclonal antibodies combined.

    PubMed

    Marcovina, S; Di Cola, G; Catapano, A L

    1986-12-01

    We produced and characterized several monoclonal antibodies directed toward human plasma apolipoprotein A-I. Two of them, A-I-12 and A-I-57, individually precipitated purified or native high-density lipoprotein in agarose gel by double immunodiffusion. Because radial immunodiffusion performed with a single monoclonal antibody gave faint and diffuse rings of precipitation, we developed and optimized working conditions for using these two monoclonal antibodies combined to determine apolipoprotein A-I in human plasma. This combination gave easy-to-measure, clear, sharp rings, and linear and parallel standard curves for HDL3 (the primary standard) and a reference serum (the secondary standard). Moreover, no pretreatment of samples with dissociating agents or detergents is necessary. The assay was complete after overnight incubation, as compared with two to three days when polyclonal antisera were used. Apolipoprotein A-I concentrations as measured in 128 normolipidemic subjects and in 72 patients with various lipid disorders by the radial immunodiffusion technique with monoclonal antibodies (x) compared well (r = 0.882; y = 1.029x-0.036) with those measured by radial immunodiffusion with polyclonal antisera (y).

  11. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  12. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  13. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  14. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  15. 22 CFR 214.13 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Responsibilities within A.I.D. 214.13 Section... Establishment of Advisory Committees § 214.13 Responsibilities within A.I.D. (a) The A.I.D. Office or Bureau seeking establishment of a new A.I.D. advisory committee: (1) Justifies the need for the advisory...

  16. Corneal vesicles accumulate collagen VI associated with tissue remodeling in apolipoprotein a-I deficiency: a case report.

    PubMed

    Namba, Hiroyuki; Narumi, Mari; Susa, Shinji; Ohe, Rintaro; Kato, Takeo; Yamakawa, Mitsunori; Yamashita, Hidetoshi

    2017-02-08

    Apo A-I deficiency clinically shows low serum levels of HDL cholesterol and corneal opacity at a young age. Histopathological evaluations of affected corneas are not enough, and the mechanism of corneal opacity is still unclear. A 61-year-old woman suffered from blurred vision with a corneal opacity. She had significantly reduced serum levels of high-density lipoprotein cholesterol and Apo A-I, stenosis of the coronary arteries, and ischemic heart failure. On genetic examination, a homozygous mutation of Apo A-ITsukuba was identified. Histopathological examination of the corneal button after PKP showed numerous vesicles in the corneal stroma, which were more prominent in the deep stroma than in the shallow stroma. Collagen VI was observed in some of those vesicles. We experienced a rare case of corneal opacity due to Apo A-I deficiency. Our histopathological findings indicated that structural changes in corneal collagen fibrils contribute to the formation of stromal vesicles.

  17. Showing and Telling Farming: Agricultural Shows and Re-Imaging British Agriculture

    ERIC Educational Resources Information Center

    Holloway, Lewis

    2004-01-01

    Some actors in the ''mainstream'' agricultural sector are beginning to engage in strategies of influencing public perceptions of farming, responding to public anxieties over industrialised agriculture and to a supposed separation of non-farming publics from food production. This paper focuses on agricultural shows as sites and events central to…

  18. Showing and Telling Farming: Agricultural Shows and Re-Imaging British Agriculture

    ERIC Educational Resources Information Center

    Holloway, Lewis

    2004-01-01

    Some actors in the ''mainstream'' agricultural sector are beginning to engage in strategies of influencing public perceptions of farming, responding to public anxieties over industrialised agriculture and to a supposed separation of non-farming publics from food production. This paper focuses on agricultural shows as sites and events central to…

  19. A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients1[S

    PubMed Central

    Cubedo, Judit; Padró, Teresa; García-Arguinzonis, Maisa; Vilahur, Gemma; Miñambres, Inka; Pou, Jose María; Ybarra, Juan; Badimon, Lina

    2015-01-01

    Diabetic (DM) patients have exacerbated atherosclerosis and high CVD burden. Changes in lipid metabolism, lipoprotein structure, and dysfunctional HDL are characteristics of diabetes. Our aim was to investigate whether serum ApoA-I, the main protein in HDL, was biochemically modified in DM patients. By using proteomic technologies, we have identified a 26 kDa ApoA-I form in serum. MS analysis revealed this 26 kDa form as a novel truncated variant lacking amino acids 1-38, ApoA-IΔ(1-38). DM patients show a 2-fold increase in ApoA-IΔ(1-38) over nondiabetic individuals. ApoA-IΔ(1-38) is found in LDL, but not in VLDL or HDL, with an increase in LDL3 and LDL4 subfractions. To identify candidate mechanisms of ApoA-I truncation, we investigated potentially involved enzymes by in silico data mining, and tested the most probable molecule in an established animal model of diabetes. We have found increased hepatic cathepsin D activity as one of the potential proteases involved in ApoA-I truncation. Cathepsin D-cleaved ApoA-I exhibited increased LDL binding affinity and decreased antioxidant activity against LDL oxidation. In conclusion, we show for the first time: a) presence of a novel truncated ApoA-I form, ApoA-IΔ(1-38), in human serum; b) ApoA-IΔ(1-38) is transported by LDL; c) ApoA-IΔ(1-38) is increased in dense LDL fractions of DM patients; and d) cathepsin D-ApoA-I truncation may lead to ApoA-IΔ(1-38) binding to LDLs, increasing their susceptibility to oxidation and contributing to the high cardiovascular risk of DM patients. PMID:26168996

  20. [A man with severe traumatic brain injury].

    PubMed

    Oudeman, Eline A; Martins Jarnalo, Carine O; van Ouwerkerk, Willem J R

    2013-01-01

    We present a 41-year-old man with severe traumatic brain injury. Cranial imaging studies revealed cerebral contusion and a longitudinal fracture of the temporal bone. Several days later brain herniated into the left external auditory canal. Imaging studies showed the known skull fracture with a direct connection between the external acoustic meatus and the intracranial structures.

  1. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false A.I.D. Advisory Committee Representative. 214... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each advisory committee used by A.I.D., the Administrator designates an A.I.D., employee to serve as the A.I.D...

  2. 22 CFR 214.31 - A.I.D. Advisory Committee Representative.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false A.I.D. Advisory Committee Representative. 214... MANAGEMENT Operation of Advisory Committees § 214.31 A.I.D. Advisory Committee Representative. (a) For each advisory committee used by A.I.D., the Administrator designates an A.I.D., employee to serve as the A.I.D...

  3. Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity

    PubMed Central

    Nguyen, Quyen L.; Corey, Catherine; White, Pamela; Watson, Annie; Gladwin, Mark T.; Simon, Marc A.

    2017-01-01

    Accumulating evidence suggests that altered cellular metabolism is systemic in pulmonary hypertension (PH) and central to disease pathogenesis. However, bioenergetic changes in PH patients and their association with disease severity remain unclear. Here, we hypothesize that alteration in bioenergetic function is present in platelets from PH patients and correlates with clinical parameters of PH. Platelets isolated from controls and PH patients (n = 28) were subjected to extracellular flux analysis to determine oxygen consumption and glycolytic rates. Platelets from PH patients showed greater glycolytic rates than controls. Surprisingly, this was accompanied by significant increases in the maximal capacity for oxygen consumption, leading to enhanced respiratory reserve capacity in PH platelets. This increased platelet reserve capacity correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and right ventricular stroke work index in PH patients and was abolished by the inhibition of fatty acid oxidation (FAO). Consistent with a shift to FAO, PH platelets showed augmented enzymatic activity of carnitine palmitoyltransferase-1 and electron transport chain complex II. These data extend the observation of a metabolic alteration in PH from the pulmonary vascular axis to the hematologic compartment and suggest that measurement of platelet bioenergetics is potentially useful in assessment of disease progression and severity. PMID:28289721

  4. Bioenergetic programming of macrophages by the apolipoprotein A-I mimetic peptide 4F.

    PubMed

    Datta, Geeta; Kramer, Philip A; Johnson, Michelle S; Sawada, Hirotaka; Smythies, Lesley E; Crossman, David K; Chacko, Balu; Ballinger, Scott W; Westbrook, David G; Mayakonda, Palgunachari; Anantharamaiah, G M; Darley-Usmar, Victor M; White, C Roger

    2015-05-01

    The apoA-I (apolipoprotein A-I) mimetic peptide 4F favours the differentiation of human monocytes to an alternatively activated M2 phenotype. The goal of the present study was to test whether the 4F-mediated differentiation of MDMs (monocyte-derived macrophages) requires the induction of an oxidative metabolic programme. 4F treatment induced several genes in MDMs that play an important role in lipid metabolism, including PPARγ (peroxisome-proliferator-activated receptor γ) and CD36. Addition of 4F was associated with a significant increase in FA (fatty acid) uptake and oxidation compared with vehicle treatment. Mitochondrial respiration was assessed by measurement of the OCR (oxygen-consumption rate). 4F increased basal and ATP-linked OCR as well as maximal uncoupled mitochondrial respiration. These changes were associated with a significant increase in ΔΨm (mitochondrial membrane potential). The increase in metabolic activity in 4F-treated MDMs was attenuated by etomoxir, an inhibitor of mitochondrial FA uptake. Finally, addition of the PPARγ antagonist T0070907 to 4F-treated MDMs reduced the expression of CD163 and CD36, cell-surface markers for M2 macrophages, and reduced basal and ATP-linked OCR. These results support our hypothesis that the 4F-mediated differentiation of MDMs to an anti-inflammatory phenotype is due, in part, to an increase in FA uptake and mitochondrial oxidative metabolism.

  5. Novel pathways of apolipoprotein A-I metabolism in HDL of different sizes in humans

    PubMed Central

    Mendivil, Carlos O.; Furtado, Jeremy; Morton, Allyson M.; Wang, Liyun; Sacks, Frank M.

    2015-01-01

    Objective A prevailing concept is that HDL is secreted into the systemic circulation as a small mainly discoidal particle; which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol; and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans. Approach and results We studied the metabolism of apolipoproteinA-I in four standard HDL sizes by endogenous isotopic labeling in six overweight adults with low HDLc and in six adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large, similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apoA-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1–4 days, and then was cleared. Enlargement of very small and medium to large and very large HDL, and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower whereas medium, large and very large HDL were cleared faster in the low HDLc group. Conclusions A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes, across the common range of HDLc concentrations. PMID:26543096

  6. [Respiratory problems in severe scoliosis].

    PubMed

    Barois, A

    1999-01-01

    In kyphoscoliosis restrictive ventilatory defect occurs. In idiopathic scoliosis vital capacity failure is significantly correlated with Cobb angle, vertebral rotation, and thoracic lordosis. Maximum voluntary ventilation is the most affected measurement. Forced expiratory volume in 1 second is reduced. Residual volume remains longtime normal. Hypoxemia due to decrease of diffusing capacity occurs, with initially reflex hyperventilation hypocapnia, and secondary hypercapnia. Pulmonary hypertension and cor pulmonale is related to hypoventilation and hypoxia. The lung situated on the concave side of the scoliosis curve shows a more functional derangement. Ventilatory pattern consists of low tidal volume and high respiratory rate with increase of ventilatory work. Scoliosis that appears in the earlier stage of the life has the worst respiratory prognosis (before 5 years of age) with impairement of lung and thoracic growth. To stimulate pulmonary and thoracic growth, intermittent ventilatory assistance by pressure preset ventilator should be performed as soon as possible and pursued up to 8 years of age, at least, more if necessity. In over 60 degrees angle idiopathic scoliosis, respiratory failure appears after 40 to 50 years of age. Non invasive ventilatory assistance with preset pressure ventilator by oral way in moderate cases and nocturnal nasal ventilation by volume ventilator or inspiratory assistance ventilator, in the most severe cases are efficient. In very severe and acute respiratory insufficiency (scoliosis over 90 degrees) ventilation by intubation then tractheostomy may be required. Earlier orthopedic management and surgical procedure to correct and stabilize spinal deformities is the best to prevent respiratory insufficiency. For scoliosis below 60 degrees, post operative pulmonary complications are very low, with no requirement of post operative ventilatory support. In very severe respiratory insufficiency treatment of respiratory failure precedes, and

  7. Severe tomato allergy (Lycopersicon esculentum).

    PubMed

    Zacharisen, Michael C; Elms, Nancy P; Kurup, Viswanath P

    2002-01-01

    Although tomatoes are a commonly consumed food, severe allergic reactions to tomatoes are unusual or rarely reported. Previously reported allergic manifestations to tomato include urticaria/angioedema, dermatitis, oral allergy syndrome, rhinitis, and abdominal pain. The aim of this study was to report two patients with significant immediate hypersensitivity reactions to tomato and characterize the responsible allergen. We reviewed the history and documentation of tomato-specific immunoglobulin E (IgE) of two patients with adverse symptoms after ingesting tomato. Fresh tomato extracts prepared from the skin, seeds, and flesh of red, ripe tomatoes were evaluated for total protein content and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to characterize the tomato protein. IgE enzyme-linked immunosorbent assay (ELISA) using the patients' serum against the various tomato extracts was accomplished and IgE immunoblot was performed. Percutaneous skin tests or radioallergosorbent tests (RASTs) were positive to tomato in both patients. Both adults experienced laryngeal edema and one had anaphylaxis. Similar total protein contents were found in each of the tomato extracts and gel electrophoresis revealed similar protein profile for skin and seed extracts with protein bands discernible at molecular weights of 21, 33, and 43 kDa. One patient reacted specifically to a 43-kDa protein band on IgE immunoblot. The two cases show that severe allergic reactions to tomato occur in adults and one is associated with IgE binding to a 43-kDa protein.

  8. Apolipoprotein A-I and its mimetics for the treatment of atherosclerosis

    PubMed Central

    Smith, Jonathan D

    2011-01-01

    Although statin treatment leads consistently to a reduction in major adverse coronary events and death in clinical trials, approximately 60 to 70% residual risk of these outcomes still remains. One frontier of investigational drug research is treatment to increase HDL, the ‘good cholesterol’ that is associated with a reduced risk of coronary artery disease. HDL and its major protein apolipoprotein A-I (apoAI) are protective against atherosclerosis through several mechanisms, including the ability to mediate reverse cholesterol transport. This review focuses on the preclinical and clinical findings for two types of therapies for the treatment of atherosclerosis: apoAI-containing compounds and apoAI mimetic peptides. Both of these therapies have excellent potential to be useful clinically to promote atherosclerosis regression and stabilize existing plaques, but significant hurdles must be overcome in order to develop these approaches into safe and effective therapies. PMID:20730693

  9. Natural resource management: A. I. D. 's experience in Nepal. Occasional paper

    SciTech Connect

    Chew, S.T.

    1990-10-01

    Since 1980, the Agency for International Development (A.I.D.) has invested about $77 million in projects to improve Nepal's natural resource management. The paper reviews the two largest projects; it also describes how USAID/Nepal is supporting multidonor forestry projects. The review identifies several important lessons. USAID/Nepal has been more effective in influencing policymaking and institutional changes when supporting multidonor projects than when acting alone. The reviewed projects underscore the difficulty of implementing large projects that involve technologies far beyond the host country's capabilities. More importantly, they demonstrate that support for resource conservation need not always be technically sophisticated, but sometimes can -- and should -- begin by integrating research and extension activities into existing agricultural and rural development projects. To gain farmer support, such activities should increase livestock and tree production without compromising food crop production. Efforts to decentralize forestry management should not stop at the local government but should involve the affected communities themselves.

  10. Severe Weather Planning for Schools

    ERIC Educational Resources Information Center

    Watson, Barbara McNaught; Strong, Christopher; Bunting, Bill

    2008-01-01

    Flash floods, severe thunderstorms, and tornadoes occur with rapid onset and often no warning. Decisions must be made quickly and actions taken immediately. This paper provides tips for schools on: (1) Preparing for Severe Weather Emergencies; (2) Activating a Severe Weather Plan; (3) Severe Weather Plan Checklist; and (4) Periodic Drills and…

  11. Glycation of Apoprotein A-I Is Associated With Coronary Artery Plaque Progression in Type 2 Diabetic Patients

    PubMed Central

    Pu, Li Jin; Lu, Lin; Zhang, Rui Yan; Du, Run; Shen, Ying; Zhang, Qi; Yang, Zheng Kun; Chen, Qiu Jing; Shen, Wei Feng

    2013-01-01

    OBJECTIVE To investigate whether glycation level of apoprotein (apo)A-I is associated with coronary artery disease (CAD) and plaque progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Among 375 consecutive type 2 diabetic patients undergoing quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), 82 patients with nonsignificant stenosis (luminal diameter narrowing <30% [group I]) and 190 patients with significant CAD (luminal diameter stenosis ≥70% [group II]) were included for analysis of apoA-I glycation level and serum activity of lecithin: cholesterol acyltransferase (LCAT). The control group had 136 healthy subjects. At the 1-year follow-up, angiography and IVUS were repeated mainly in group II patients for plaque progression assessment. RESULTS Relative intensity of apoA-I glycation by densitometry was increased, and serum LCAT activity was decreased stepwise across groups control, I, and II. These two measurements were associated with the number of diseased coronary arteries and extent index in group II. During 1-year follow-up, QCA detected 45 patients with plaque progression in 159 subjects, and IVUS found 38 patients with plaque progression in 127 subjects. Baseline relative intensity of apoA-I glycation was significantly increased in patients with plaque progression compared with those without, with values associated with changes in QCA and IVUS measurements. Multivariable regression analysis revealed that baseline relative intensity of apoA-I glycation was an independent determinant of CAD and plaque progression in type 2 diabetic patients. CONCLUSIONS ApoA-I glycation level is associated with the severity of CAD and coronary artery plaque progression in type 2 diabetic patients. PMID:23230102

  12. Endotoxin contamination of apolipoprotein A-I: effect on macrophage proliferation--a cautionary tale.

    PubMed

    Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S

    2015-05-01

    This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation>90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages.

  13. Endotoxin Contamination of Apolipoprotein A-I: Effect on Macrophage Proliferation – A Cautionary Tale

    PubMed Central

    Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S.

    2015-01-01

    This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation >90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages. PMID:25778625

  14. Case of Cronkhite Canada syndrome shows improvement with enteral supplements.

    PubMed

    Lipin, S P; Paul, Baby; Nazimudeen, E; Jacob, Baiju Sam

    2012-04-01

    Cronkhite-Canada syndrome (CCS) is a rare nonfamilial syndrome characterized by marked epithelial disturbances in the GI tract and epidermis. Cronkhite and Canada described the first 2 cases in 1955. Since then only about 450 cases have been reported worldwide. Here we report a 33 year old Indian male admitted with history of loose stools and abdominal pain, loose stools associated with weight loss, generalized weakness, significant amount of hair loss as well as hyperpigmentation of his palms and soles. On subsequent days of the stay in the hospital he developed hypogeusia and showed onychodystrophy. Endoscopy of Upper GI and Lower GI tract revealed severe gastroduodenitis with polyp in duodenum and multiple polyps whole throughout the colon respectively. Biopsy report showed eosinophilic gastritis and hamartomatous polyps in colon as well as in duodenum. He was started on high protein supplement, proton pump inhibitors and zinc-vitamin supplement and he showed a complete recovery in symptoms within 5 months of initiation of treatment. Hence, early diagnosis and initiation of appropriate treatment helped the patient to improve in symptoms from such a rare disease.

  15. Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

    PubMed

    Barfield, Whitney L; Uaesoontrachoon, Kitipong; Wu, Chung-Sheih; Lin, Stephen; Chen, Yue; Wang, Paul C; Kanaan, Yasmine; Bond, Vernon; Hoffman, Eric P

    2014-08-01

    A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.

  16. Borrelia burgdorferi shows specificity of binding to glycosphingolipids.

    PubMed Central

    Backenson, P B; Coleman, J L; Benach, J L

    1995-01-01

    Live but not fixed or heat-killed Borrelia burgdorferi bound to galactocerebroside, lactosylceramide, and ceramide trihexoside. In addition, this organism bound to the disialoganglioside GD1a and the trisialoganglioside GT1b but not to gangliosides GM1, GD1b, GM2, and GM3 and not to asialo GM1. This adhesion pattern confirmed earlier findings of binding to galactocerebroside and places this organism within a prokaryotic group which binds to lactosylceramide. The binding to GD1a and GT1b, both of which carry terminal as well as multiple sialic acids, indicates that B. burgdorferi can show specificity of binding within a group of acidic gangliosides. Adhesion could not be inhibited by several concentrations of sugars and sialic acid, indicating more complex binding requirements than for terminal carbohydrates alone. Low-passage strains adhered to the four substrates in greater numbers than strains in culture for long periods of time. OspB mutants in general bound better or at least equally well to several of the glycosphingolipids, and preincubation of substrates with soluble recombinant and affinity-purified Osp did not inhibitor or weakly inhibited the binding of the organisms. These findings suggest that outer surface lipoproteins A and B are not directly involved in adhesion to glycosphingolipids. PMID:7622201

  17. IV thrombolysis in very severe and severe ischemic stroke

    PubMed Central

    Lees, Kennedy R.; Collas, David; Rand, Viiu-Marika; Mikulik, Robert; Toni, Danilo; Wahlgren, Nils; Ahmed, Niaz

    2015-01-01

    Objective: To study the safety of off-label IV thrombolysis in patients with very severe stroke (NIH Stroke Scale [NIHSS] scores >25) compared with severe stroke (NIHSS scores 15–25), where treatment is within European regulations. Methods: Data were analyzed from 57,247 patients with acute ischemic stroke receiving IV tissue plasminogen activator in 793 hospitals participating in the Safe Implementation of Thrombolysis in Stroke (SITS) International Stroke Thrombolysis Registry (2002–2013). Eight hundred sixty-eight patients (1.5%) had NIHSS scores >25 and 19,995 (34.9%) had NIHSS scores 15–25. Outcome measures were parenchymal hemorrhage, symptomatic intracerebral hemorrhage, mortality, and functional outcome. Results: Parenchymal hemorrhage occurred in 10.7% vs 11.0% (p = 0.79), symptomatic intracerebral hemorrhage per SITS-MOST (SITS–Monitoring Study) in 1.4% vs 2.5% (p = 0.052), death at 3 months in 50.4% vs 26.9% (p < 0.001), and functional independence at 3 months in 14.0% vs 29.0% (p < 0.001) of patients with NIHSS scores >25 and NIHSS scores 15–25, respectively. Multivariate adjustment did not change findings from univariate comparisons. Posterior circulation stroke was more common in patients with NIHSS scores >25 (36.2% vs 7.4%, p < 0.001), who were also more often obtunded or comatose on presentation (58.4% vs 7.1%, p < 0.001). Of patients with NIHSS scores >25, 26.2% were treated >3 hours from symptom onset vs 14.5% with NIHSS scores of 15–25. Conclusions: Our data show no excess risk of cerebral hemorrhage in patients with NIHSS score >25 compared to score 15–25, suggesting that the European contraindication to IV tissue plasminogen activator treatment at NIHSS levels >25 may be unwarranted. Increased mortality and lower rates of functional independence in patients with NIHSS score >25 are explained by higher stroke severity, impaired consciousness on presentation due to posterior circulation ischemia, and longer treatment delays. PMID

  18. Ferrous polycrystalline shape-memory alloy showing huge superelasticity.

    PubMed

    Tanaka, Y; Himuro, Y; Kainuma, R; Sutou, Y; Omori, T; Ishida, K

    2010-03-19

    Shape-memory alloys, such as Ni-Ti and Cu-Zn-Al, show a large reversible strain of more than several percent due to superelasticity. In particular, the Ni-Ti-based alloy, which exhibits some ductility and excellent superelastic strain, is the only superelastic material available for practical applications at present. We herein describe a ferrous polycrystalline, high-strength, shape-memory alloy exhibiting a superelastic strain of more than 13%, with a tensile strength above 1 gigapascal, which is almost twice the maximum superelastic strain obtained in the Ni-Ti alloys. Furthermore, this ferrous alloy has a very large damping capacity and exhibits a large reversible change in magnetization during loading and unloading. This ferrous shape-memory alloy has great potential as a high-damping and sensor material.

  19. ESP precharger shows promise in solving ash-resistivity problems

    SciTech Connect

    Schwieger, B.

    1984-09-01

    Recent tests of a temperature-controlled electrode charger (TCEP) show that it may be an economical fix for both high-resistivity-related problems and increased particulate loadings resulting from application of a particular SO2 control strategy. The TCEP would reportedly be relatively easy to install in an existing precipitator. Operation of the TCEP in a low-sulfur coal flue gas stream is demonstrated as well as the pipe-manifold design of the TCEP. Several advantages to this design are presented. Two of them include: the welded pipe structure is simple to fabricate and is very durable; and the structural rigidity of the system effectively distributes the rapping force and provides effective cleaning. An economical analysis by Denver Research Institute is presented which indicates that the installation of two TCEPs in the ESP was half the cost of SO3 conditioning and less expensive than a fabric filter.

  20. Impact Factors Show Increased Use of AGU Journals in 2008

    NASA Astrophysics Data System (ADS)

    Ford, Barbara Meyers

    2009-07-01

    The latest numbers released from Journal Citation Reports (JCR), published annually by Thomson Reuters, show large increases in the impact factor (IF) for several AGU journals. IFs are one way for publishers to know that readers have found their journals useful and of value in research. A journal's IF is calculated by taking the total number of citations to articles published by a given journal in the past 2 years and dividing it by the total number of papers published by the journal in the same time period. More generally, it can be seen as the frequency with which articles in a journal have been cited over the past year. The numbers speak for themselves (see Table 1).

  1. Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process.

    PubMed

    Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto

    2014-01-01

    Discoidal high-density lipoproteins (D-HDL) are critical intermediates in reverse cholesterol transport. Most of the present knowledge of D-HDL is based on studies with reconstituted lipoprotein complexes of apolipoprotein A-I (apoA-I) obtained by cholate dialysis (CD). D-HDL can also be generated by the direct microsolubilization (DM) of phospholipid vesicles at the gel/fluid phase transition temperature, a process mechanistically similar to the "in vivo" apoAI lipidation via ABCA1. We compared the apoA-I configuration in D-HDL reconstituted with dimyristoylphosphatidylcholine by both procedures using fluorescence resonance energy transfer measurements with apoA-I tryptophan mutants and fluorescently labeled cysteine mutants. Results indicate that apoA-I configuration in D-HDL depends on the reconstitution process and are consistent with a "double belt" molecular arrangement with different helix registry. As reported by others, a configuration with juxtaposition of helices 5 of each apoAI monomer (5/5 registry) predominates in D-HDL obtained by CD. However, a configuration with helix 5 of one monomer juxtaposed with helix 2 of the other (5/2 registry) would predominate in D-HDL generated by DM. Moreover, we also show that the kinetics of cholesterol efflux from macrophage cultures depends on the reconstitution process, suggesting that apoAI configuration is important for this HDL function. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Bioinformatic Analysis of Plasma Apolipoproteins A-I and A-II Revealed Unique Features of A-I/A-II HDL Particles in Human Plasma

    PubMed Central

    Kido, Toshimi; Kurata, Hideaki; Kondo, Kazuo; Itakura, Hiroshige; Okazaki, Mitsuyo; Urata, Takeyoshi; Yokoyama, Shinji

    2016-01-01

    Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency. Thus, overall HDL concentration almost exclusively depends on HDL with apoA-I without apoA-II (LpAI) while concentration of HDL containing apoA-I and apoA-II (LpAI:AII) is constant having a fixed molar ratio of 2 : 1 regardless of total HDL and apoA-I concentration. Distribution of apoA-I between LpAI and LpAI:AII is consistent with a model of statistical partitioning regardless of sex and CETP genotype. The analysis also indicated that LpA-I accommodates on average 4 apoA-I molecules and has a clearance rate indistinguishable from LpAI:AII. Independent evidence indicated LpAI:A-II has a diameter 20% smaller than LpAI, consistent with a model having two apoA-I and one apoA-II. The functional contribution of these particles is to be investigated. PMID:27526664

  3. Adenoma Detection Rate: I Will Show You Mine if You Show Me Yours

    PubMed Central

    Oliveira Ferreira, Alexandre; Fidalgo, Catarina; Palmela, Carolina; Costa Santos, Maria Pia; Torres, Joana; Nunes, Joana; Loureiro, Rui; Ferreira, Rosa; Barjas, Elídio; Glória, Luísa; Santos, António Alberto; Cravo, Marília

    2017-01-01

    Background Colorectal cancer (CRC) is the first cause of cancer-related mortality in Portugal. CRC screening reduces disease-specific mortality. Colonoscopy is currently the preferred method for screening as it may contribute to the reduction of CRC incidence. This beneficial effect is strongly associated with the adenoma detection rate (ADR). Aim Our aim was to evaluate the quality of colonoscopy at our unit by measuring the currently accepted quality parameters and publish them as benchmarking indicators. Methods From 5,860 colonoscopies, 654 screening procedures (with and without previous fecal occult blood testing) were analyzed. Results The mean age of the patients was 66.4 ± 7.8 years, and the gender distribution was 1:1. The overall ADR was 36% (95% confidence interval [CI] 32–39), the mean number of adenomas per colonoscopy was 0.66 (95% CI 0.56–0.77), and the sessile serrate lesion detection rate was 1% (95% CI 0–2). The bowel preparation was rated as adequate in 496 (76%) patients. The adjusted cecal intubation rate (CIR) was 93.7% (95% CI 91.7–95.8). Most colonoscopies were performed under monitored anesthesia care (53%), and 35% were unsedated. The use of sedation (propofol or midazolam based) was associated with a higher CIR with an odds ratio of 3.60 (95% CI 2.02–6.40, p < 0.001). Conclusion Our data show an above-standard ADR. The frequency of poor bowel preparation and the low sessile serrated lesion detection rate were acknowledged, and actions were implemented to improve both indicators. Quality auditing in colonoscopy should be compulsory, and while many units may do so internally, this is the first national report from a high-throughput endoscopy unit. PMID:28848785

  4. Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition.

    PubMed

    Karavia, Eleni A; Hatziri, Aikaterini; Kalogeropoulou, Christina; Papachristou, Nikolaos I; Xepapadaki, Eva; Constantinou, Caterina; Natsos, Anastasios; Petropoulou, Peristera-Ioanna; Sasson, Shlomo; Papachristou, Dionysios J; Kypreos, Kyriakos E

    2015-11-05

    Recently, we showed that deficiency in apolipoprotein A-I (ApoA-I) sensitizes mice to diet-induced obesity, glucose intolerance and NAFLD. Here we investigated the potential involvement of ApoA-I in the pharmacological effects of metformin on glucose intolerance and NAFLD development. Groups of apoa1-deficient (apoa1(-/-)) and C57BL/6 mice fed western-type diet were either treated with a daily dose of 300 mg/kg metformin for 18 weeks or left untreated for the same period. Then, histological and biochemical analyses were performed. Metformin treatment led to a comparable reduction in plasma insulin levels in both C57BL/6 and apoa1(-/-) mice following intraperitoneal glucose tolerance test. However, only metformin-treated C57BL/6 mice maintained sufficient peripheral insulin sensitivity to effectively clear glucose following the challenge, as indicated by a [(3)H]-2-deoxy-D-glucose uptake assay in isolated soleus muscle. Similarly, deficiency in ApoA-I ablated the effect of metformin on hepatic lipid deposition and NAFLD development. Gene expression analysis indicated that the effects of ApoA-I on metformin treatment may be independent of adenosine monophosphate-activated protein kinase (AMPK) activation and de novo lipogenesis. Interestingly, metformin treatment reduced mitochondrial oxidative phosphorylation function only in apoa1(-/-) mice. Our data show that the role of ApoA-I in diabetes extends to the modulation of the pharmacological actions of metformin, a common drug for the treatment of type 2 diabetes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats

    PubMed Central

    Zhang, Zhenghao; Datta, Geeta; Zhang, Yun; Miller, Andrew P.; Mochon, Paulina; Chen, Yiu-Fai; Chatham, John; Anantharamaiah, G. M.; White, C. Roger

    2009-01-01

    Systemic inflammation induces a multiple organ dysfunction syndrome that contributes to morbidity and mortality in septic patients. Since increasing plasma apolipoprotein A-I (apoA-I) and HDL may reduce the complications of sepsis, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in rats undergoing cecal ligation and puncture (CLP) injury. Male Sprague-Dawley rats were randomized to undergo CLP or sham surgery. IL-6 levels were significantly elevated in plasma by 6 h after CLP surgery compared with shams. In subsequent studies, CLP rats were further subdivided to receive vehicle or 4F (10 mg/kg) by intraperitoneal injection, 6 h after sepsis induction. Sham-operated rats received saline. Echocardiographic studies showed a reduction in left ventricular end-diastolic volume, stroke volume, and cardiac output (CO) 24 h after CLP surgery. These changes were associated with reduced blood volume and left ventricular filling pressure. 4F treatment improved blood volume status, increased CO, and reduced plasma IL-6 in CLP rats. Total cholesterol (TC) and HDL were 79 ± 5 and 61 ± 4 mg/dl, respectively, in sham rats. TC was significantly reduced in CLP rats (54 ± 3 mg/dl) due to a reduction in HDL (26 ± 3 mg/dl). 4F administration to CLP rats attenuated the reduction in TC (69 ± 4 mg/dl) and HDL (41 ± 3 mg/dl) and prevented sepsis-induced changes in HDL protein composition. Increased plasma HDL in 4F-treated CLP rats was associated with an improvement in CO and reduced mortality. It is proposed that protective effects of 4F are related to its ability to prevent the sepsis-induced reduction in plasma HDL. PMID:19561306

  6. Hydrocarbon shows in the scientific ocean drilling programs

    SciTech Connect

    Katz, B.J. ); Emeis, K.C. )

    1990-05-01

    For more than 20 yr, two major programs, the Deep Sea Drilling Project (DSDP) and the Ocean Drilling Program (ODP), have been coring the deep oceans for scientific purposes. For technological as well as financial reasons, drilling was and is performed without a riser. Precruise preparation, therefore, is aimed at preventing an accidental hydrocarbon discovery. During the course of drilling, at the more than 700 locations studied to date, numerous black shales of various ages were encountered. Many of these represent thermally immature hydrocarbon source rocks. Although these organic-rich rocks (up to 34 wt.% total organic carbon) by themselves did not pose a safety problem, hydrocarbon shows were detected on no less than ten legs. These shows represent heavy (C{sub 15+}), thermally generated hydrocarbons. Commonly, these shows can be attributed to migration through a porous and permeable network into the penetrated section. In these situations, migration commonly occurs over distances on the order of several tens of miles from a more mature, structurally deeper section (e.g., Challenger Knoll, DSDP Site 2). There are, however, instances where there is strong geochemical evidence for in-situ hydrocarbon generation. In-situ hydrocarbon generation appears to be the result of anomalous thermal conditions associated with high heat flow, igneous and/or hydrothermal activity (e.g., Tyrrhenian Sea, ODP Site 652). Such conditions are more commonly associated with young marginal basins. The distribution of these shows provides valuable information on the long-term exploratory potential of the deep oceans and continental margins.

  7. A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype.

    PubMed

    Tougaard, Birgitte G; Pedersen, Katja Venborg; Krag, Søren Rasmus; Gilbertson, Janet A; Rowczenio, Dorota; Gillmore, Julian D; Birn, Henrik

    2016-09-01

    Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A-I amyloid protein. We describe the identification of apo A-I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Phylogenetic distribution of apolipoproteins A-I and E in vertebrates as determined by Western blot analysis.

    PubMed

    Duggan, A E; Callard, I P

    2001-08-01

    A putative apolipoprotein E (apoE) has been identified in the HDL and VHDL fractions of the turtle. This observation is of particular interest considering apoE has been reported absent in the domestic hen (Hermier et al., '95; Biochim Biophys Acta: 105-118, 1995) and thus presumed absent in nonmammalian vertebrates altogether. As a result, partial amino acid sequencing of this protein was performed and revealed that one fragment shared 41% sequence identity to human apoE. Western blot analysis using antisera to apoE demonstrated cross-reactivity to a 34-kDa protein (putative apoE) in turtle plasma. Further investigation using anti-apoE antibody in Western blot analysis detected immunoreactive apoE in the plasma of lamprey, spiny dogfish, skate, and alligator, but not in flounder, newt or python; its absence in several species of birds was confirmed. Using anti-apoA-I antibody, apoA-I was detected in all vertebrate groups except a representative teleost (flounder). Apo-A-I antibody cross-reacted weakly with some putative apoE proteins (chicken, spiny dogfish and skate) and the reverse was true for anti-apoE, which cross-reacted with putative apoA-I in birds, reptiles, and elasmobranchs, confirming the molecular similarity and phylogenetic relatedness of these two proteins.

  9. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  10. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  11. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  12. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  13. 22 CFR 224.39 - Appeal to A.I.D. Administrator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Appeal to A.I.D. Administrator. 224.39 Section... CIVIL REMEDIES ACT § 224.39 Appeal to A.I.D. Administrator. (a) Any defendant who has filed a timely... appeal such decision to the A.I.D. Administrator by filing a notice of appeal with the A.I.D...

  14. Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I*

    PubMed Central

    Chan, Gary K. L.; Witkowski, Andrzej; Gantz, Donald L.; Zhang, Tianqi O.; Zanni, Martin T.; Jayaraman, Shobini; Cavigiolio, Giorgio

    2015-01-01

    High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo. PMID:25759391

  15. High-density lipoprotein apolipoprotein A-I kinetics in obesity.

    PubMed

    Ooi, Esther M M; Watts, Gerald F; Farvid, Maryam S; Chan, Dick C; Allen, Michael C; Zilko, Simon R; Barrett, P Hugh R

    2005-06-01

    Low plasma concentrations of high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (apoA-I) are independent predictors of coronary artery disease and are often associated with obesity and the metabolic syndrome. However, the underlying kinetic determinants of HDL metabolism are not well understood. We pooled data from 13 stable isotope studies to investigate the kinetic determinants of apoA-I concentrations in lean and overweight-obese individuals. We also examined the associations of HDL kinetics with age, sex, BMI, fasting plasma glucose, fasting insulin, Homeostasis Model Assessment score, and concentrations of apoA-I, triglycerides, HDL-cholesterol and low-density lipoprotein-cholesterol. Compared with lean individuals, overweight-obese individuals had significantly higher HDL apoA-I fractional catabolic rate (0.21+/-0.01 vs. 0.33+/-0.01 pools/d; p<0.001) and production rate (PR; 11.3+/-4.4 vs. 15.8+/-2.77 mg/kg per day; p=0.001). In the lean group, HDL apoA-I PR was significantly associated with apoA-I concentration (r=0.455, p=0.004), whereas in the overweight-obese group, both HDL apoA-I fractional catabolic rate (r=-0.396, p=0.050) and HDL apoA-I PR (r=0.399, p=0.048) were significantly associated with apoA-I concentration. After adjustment for fasting insulin or Homeostasis Model Assessment score, HDL apoA-I PR was an independent predictor of apoA-I concentration. In overweight-obese subjects, hypercatabolism of apoA-I is paralleled by an increased production of apoA-I, with HDL apoA-I PR being the stronger determinant of apoA-I concentration. This could have therapeutic implications for the management of dyslipidemia in individuals with low plasma HDL-cholesterol.

  16. [How children show positive and negative relationships on their drawings].

    PubMed

    Gramel, Sabine

    2005-01-01

    This study analyses, whether pictures of children showing a positive relationship are significantly different from those showing a negative one with respect to several criteria. The study involved a random selection of 45 children aged 4;6 to 11;6 years. The children painted a picture with themselves and a person they liked and a picture of themselves with someone they disliked. For the most part, the children drew pictures of themselves with peers both with respect to positive as well as negative images. In an interview afterwards, the children specified the criteria in their drawings by which the quality of the particular relationship can be identified. Positive and negative relationship paintings differ in the character of activity described. The sun as an element in children's paintings is painted not more frequent on positive compared to negative pictures. The colour black is used more often in the drawings signifying negative relationships. While girls used more colour in negative relationship drawings, boys used more colour in the positive ones. There was no significant difference in the use of favourite colours and decorative elements between the two groups. Only in negative relationship drawings people were looking away from each other. Smiling individuals were more common in the positive relationship pictures and in pictures painted by the 6 to 8 year olds. A greater distance between the individuals emerged on negative relationship drawings of the girls.

  17. Local Vascular Gene Therapy With Apolipoprotein A-I to Promote Regression of Atherosclerosis.

    PubMed

    Wacker, Bradley K; Dronadula, Nagadhara; Zhang, Jingwan; Dichek, David A

    2017-02-01

    Gene therapy, delivered directly to the blood vessel wall, could potentially prevent atherosclerotic lesion growth and promote atherosclerosis regression. Previously, we reported that a helper-dependent adenoviral (HDAd) vector expressing apolipoprotein A-I (apoA-I) in carotid endothelium of fat-fed rabbits reduced early (4 weeks) atherosclerotic lesion growth. Here, we tested whether the same HDAd-delivered to the existing carotid atherosclerotic lesions-could promote regression. Rabbits (n=26) were fed a high-fat diet for 7 months, then treated with bilateral carotid gene transfer. One carotid was infused with an HDAd expressing apoA-I (HDAdApoAI) and the other with a control nonexpressing HDAd (HDAdNull). The side with HDAdApoAI was randomized. Rabbits were then switched to regular chow, lowering their plasma cholesterols by over 70%. ApoA-I mRNA and protein were detected in HDAdApoAI-transduced arteries. After 7 weeks of gene therapy, compared with HDAdNull-treated arteries in the same rabbits, HDAdApoAI-treated arteries had significantly less vascular cell adhesion molecule-1 expression (28%; P=0.04) along with modest but statistically insignificant trends toward decreased intimal lesion volume, lipid and macrophage content, and intercellular adhesion molecule-1 expression (9%-21%; P=0.1-0.4). Post hoc subgroup analysis of rabbits with small-to-moderate-sized lesions (n=20) showed that HDAdApoAI caused large reductions in lesion volume, lipid content, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression (30%-50%; P≤0.04 for all). Macrophage content was reduced by 30% (P=0.06). There was a significant interaction (P=0.02) between lesion size and treatment efficacy. Even when administered on a background of aggressive lowering of plasma cholesterol, local HDAdApoAI vascular gene therapy may promote rapid regression of small-to-moderate-sized atherosclerotic lesions. © 2016 American Heart Association, Inc.

  18. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  19. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  20. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  1. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  2. 22 CFR 214.22 - Responsibilities within A.I.D.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Responsibilities within A.I.D. 214.22 Section... Termination and Renewal of Advisory Committees § 214.22 Responsibilities within A.I.D. Responsibilities within A.I.D. for the renewal of advisory committees are as follows: (a) The Office or Bureau through which...

  3. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  4. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  5. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  6. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  7. 22 CFR 221.24 - Subrogation of A.I.D.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Subrogation of A.I.D. 221.24 Section 221.24 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.24 Subrogation of A.I.D. In the event of payment by A.I.D. to...

  8. Smoking and periodontal disease severity.

    PubMed

    Martinez-Canut, P; Lorca, A; Magán, R

    1995-10-01

    This study was performed to assess the influence of smoking on periodontal disease severity. Data concerning periodontal status and smoking habits were collected from 889 periodontal patients: 340 male and 549 female, 21 to 76 years of age, 47.4% being non smokers and 52.6% smokers. Periodontal parameters, recorded by the same examiner (PMC), were: gingival recession (GR), Pocket depth (PD), Probing attachment level (PAL), and mobility (M). The influence of age, sex and tobacco consumption on these periodontal parameters was statistically evaluated using an analysis of variance (ANOVA) with covariates. A non-linear effect model was also fitted by taking the natural logarithms of the response variables (GR, PD, PAL) closer to biomedical phenomena. Mobility was analyzed by a chi2-test. The effect of smoking on periodontitis showed no association with age or with sex. Smoking, age and sex were shown to be statistically significant for periodontitis, by performing both univariate (t-test for equal means) and multivariate tests. p-values for smoking and periodontitis were: GR (p=0.000), PD (p=0.000), PAL (p=0.000) and M (P=0.015). Smoking one cigarette per day, up to 10, and up to 20, increased PAL by 0.5%, 5% and 10%, respectively. The impact of tobacco is comparable to the impact resulting from the factor of age in this sample, increasing PAL by 0.7% for each year of life. Comparison between smokers of less than 10 cigarettes per day (PAL mean 3.72 mm +/-0.86) and non-smokers (PAL mean 3.84 +/- 0.89) showed no differences in PAL (p=0.216), while comparison for smokers from 11 to 20 cigarettes (PAL mean 4.36 +/- 1.23) and for more than 20 cigarettes (PAL mean 4.50 +/- 1.04) demonstrated significant differences (p=0.000). These findings suggest that: (1) tobacco increases periodontal disease severity; (2) this effect is clinically evident above consumption of a certain quantity of tobacco.

  9. Preventing recurrence of severe morning sickness

    PubMed Central

    Koren, Gideon; Maltepe, Caroline

    2006-01-01

    QUESTION A recent Motherisk article showed that initiating antinauseants even before symptoms start could prevent recurrence of severe morning sickness. In the study described, however, different physicians used different drugs. How can one be sure which drugs work? ANSWER The study of 26 women who had had severe morning sickness during previous pregnancies showed that using antiemetics before symptoms of morning sickness started appeared to prevent recurrence of severe morning sickness in subsequent pregnancies. Physicians in the United States used various antinauseant drugs. Physicians in Canada administered only one drug, the combination of doxylamine-pyridoxine (Diclectin®), to 12 women. Subanalysis of these 12 women revealed that pre-emptive use of doxylamine-pyridoxine significantly decreased the likelihood that severe morning sickness would recur. PMID:17279232

  10. Statistics of severe tornadoes and severe tornado outbreaks

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.; Turcotte, D. L.

    2012-09-01

    The standard measures of the intensity of a tornado in the USA and many other countries are the Fujita and Enhanced Fujita scales. These scales are based on the damage that a tornado causes. Another measure of the strength of a tornado is its path length of touchdown, L. In this study we consider severe tornadoes, which we define as L≥10 km, in the continental USA (USA Storm Prediction Center Severe Weather Database). We find that for the period 1982-2011, for individual severe tornadoes (L≥10 km): (i) There is a strong linear scaling between the number of severe tornadoes in a year and their total path length in that year. (ii) The cumulative frequency path length data suggests that, not taking into account any changing trends over time, we would expect in a given year (on average) one severe tornado with a path length L≥115 km and in a decade (on average) one severe tornado with a path length L≥215 km. (iii) The noncumulative frequency-length statistics of severe tornado touchdown path lengths, 20severe tornadoes in a convective day (12:00-12:00 UTC), LD, as a measure of the strength of a 24-h USA tornado outbreak. We find that: (i) For 1982-2011, the number of severe tornadoes in a USA convective day outbreak has a strong power-law relationship (exponent 0.80) on the convective day total path length, LD. (ii) For 1952-2011, the cumulative frequency path length data for severe tornado outbreaks suggests that we would expect in a given year (on average) one daily severe tornado outbreak with total path length LD≥480 km and in a decade (on average) one daily severe tornado outbreak with a total path length LD≥1200 km. (iii) For 1982-2011, the noncumulative frequency-length statistics of tornado outbreaks, 10

  11. Radar Shows Italy Area Moved 8 Inches by Amatrice Earthquake

    NASA Image and Video Library

    2016-08-27

    NASA and its partners are contributing observations and expertise to the ongoing response to the Aug. 23, 2016, magnitude 6.2 Amatrice earthquake in central Italy caused widespread building damage to several towns throughout the region. This earthquake was the strongest in that area since the 2009 earthquake that destroyed the city of L'Aquila. Scientists with the Advanced Rapid Imaging and Analysis project (ARIA), a collaboration between NASA's Jet Propulsion Laboratory, Pasadena, California, and the California Institute of Technology in Pasadena, analyzed interferometric synthetic aperture radar images from the PALSAR-2 instrument on the ALOS-2 satellite operated by the Japan Aerospace Exploration Agency (JAXA) to calculate a map of the deformation of Earth's surface caused by the quake. This false-color map shows the amount of permanent surface movement, as viewed by the satellite, during a seven-month interval between two ALOS-2 images acquired on Sept. 9, 2015 and Aug. 24, 2016. The movement was caused almost entirely by the earthquake. In this map, the colors of the surface displacements are proportional to the surface motion. The red and pink tones show the areas where the land moved toward the satellite by up to 2 inches (5 centimeters). The area with various shades of blue moved away from the satellite, mostly downward, by as much as 8 inches (20 centimeters). Contours on the surface motion are 2 inches (5 centimeters) The green star shows the epicenter where the earthquake started as located by the U.S. Geological Survey National Earthquake Information Center. Black dots show town locations. Scientists use these maps to build detailed models of the fault slip at depth and associated land movements to better understand the impact on future earthquake activity. The map shows the fault or faults that moved in the earthquake is about 14 miles (22 kilometers) long between Amatrice and Norcia and slopes to the west beneath the area that moved downward. The

  12. Stimulation of Hepatic Apolipoprotein A-I Production by Novel Thieno-Triazolodiazepines: Roles of the Classical Benzodiazepine Receptor, PAF Receptor, and Bromodomain Binding

    PubMed Central

    Kempen, Herman J; Bellus, Daniel; Fedorov, Oleg; Nicklisch, Silke; Filippakopoulos, Panagis; Picaud, Sarah; Knapp, Stefan

    2013-01-01

    Expression and secretion of apolipoprotein A-I (apoA-I) by cultured liver cells can be markedly stimulated by triazolodiazepines (TZDs). It has been shown previously that the thieno-TZD Ro 11-1464 increases plasma levels of apoA-I and in vivomacrophage reverse cholesterol transport in mice. However, these effects were only seen at high doses, at which the compound could act on central benzodiazepine (BZD) receptors or platelet activating factor (PAF) receptors, interfering with its potential utility. In this work, we describe 2 new thieno-TZDs MDCO-3770 and MDCO-3783, both derived from Ro 11-1464. These compounds display the same high efficacy on apoA-I production, metabolic stability, and lack of cytotoxicity in cultured hepatocytes as Ro 11-1464, but they do not bind to the central BZD receptor and PAF receptor. The quinazoline RVX-208 was less efficacious in stimulating apoA-I production and displayed signs of cytotoxicity. Certain TZDs stimulating apoA-I production are now known to be inhibitors of bromodomain (BRD) extra-terminal (BET) proteins BRDT, BRD2, BRD3, and BRD4, and this inhibition was inferred as a main molecular mechanism for their effect on apoA-I expression. We show here that the thieno-TZD (+)-JQ1, a potent BET inhibitor, strongly stimulated apoA-I production in Hep-G2 cells, but that its enantiomer (−)-JQ1, which has no BET inhibitor activity, also showed considerable effect on apoA-I production. MDCO-3770 and MDCO-3783 also inhibited BRD3 and BRD4 in vitro, with potency somewhat below that of (+)-JQ1. We conclude that the effect of thieno-TZDs on apoA-I expression is not due to inhibition of the BZD or PAF receptors and is not completely explained by transcriptional repression by BET proteins. PMID:25278768

  13. Stimulation of Hepatic Apolipoprotein A-I Production by Novel Thieno-Triazolodiazepines: Roles of the Classical Benzodiazepine Receptor, PAF Receptor, and Bromodomain Binding.

    PubMed

    Kempen, Herman J; Bellus, Daniel; Fedorov, Oleg; Nicklisch, Silke; Filippakopoulos, Panagis; Picaud, Sarah; Knapp, Stefan

    2013-01-01

    Expression and secretion of apolipoprotein A-I (apoA-I) by cultured liver cells can be markedly stimulated by triazolodiazepines (TZDs). It has been shown previously that the thieno-TZD Ro 11-1464 increases plasma levels of apoA-I and in vivomacrophage reverse cholesterol transport in mice. However, these effects were only seen at high doses, at which the compound could act on central benzodiazepine (BZD) receptors or platelet activating factor (PAF) receptors, interfering with its potential utility. In this work, we describe 2 new thieno-TZDs MDCO-3770 and MDCO-3783, both derived from Ro 11-1464. These compounds display the same high efficacy on apoA-I production, metabolic stability, and lack of cytotoxicity in cultured hepatocytes as Ro 11-1464, but they do not bind to the central BZD receptor and PAF receptor. The quinazoline RVX-208 was less efficacious in stimulating apoA-I production and displayed signs of cytotoxicity. Certain TZDs stimulating apoA-I production are now known to be inhibitors of bromodomain (BRD) extra-terminal (BET) proteins BRDT, BRD2, BRD3, and BRD4, and this inhibition was inferred as a main molecular mechanism for their effect on apoA-I expression. We show here that the thieno-TZD (+)-JQ1, a potent BET inhibitor, strongly stimulated apoA-I production in Hep-G2 cells, but that its enantiomer (-)-JQ1, which has no BET inhibitor activity, also showed considerable effect on apoA-I production. MDCO-3770 and MDCO-3783 also inhibited BRD3 and BRD4 in vitro, with potency somewhat below that of (+)-JQ1. We conclude that the effect of thieno-TZDs on apoA-I expression is not due to inhibition of the BZD or PAF receptors and is not completely explained by transcriptional repression by BET proteins.

  14. New Inspiring Planetarium Show Introduces ALMA to the Public

    NASA Astrophysics Data System (ADS)

    2009-03-01

    , 400 years ago, to the world of modern astronomy, moving from the visible wavelength domain to explore the millimetre-wave view of the Universe, and leaving light-polluted cities for unique settings in some of the highest and driest places on Earth. "The fascinating topic, the breathtaking ESO astronomical images, the amazing 3D computer animations, and the very clever use of the music, all make this a really inspiring show," says Agnès Acker, President of the APLF. In search of our Cosmic Origins is available in three different formats: fulldome video, classical with video windows, and classical with slides. Fulldome video shows immerse the audience in a true 360-degree projected computer-generated virtual environment. The ALMA planetarium show is currently available in French and English. Several other language versions are in preparation: German, Italian, Spanish and Chilean Spanish, while further languages are planned: Danish, Dutch, Greek, Japanese, Portuguese and Brazilian Portuguese. The show will be available to all planetariums worldwide for a small fee, depending on the type and the size of the planetarium, to cover basic costs. The media are invited to attend, and see firsthand, the official screening during the European Film Festival, between 24 and 26 April 2009 in Espinho, Portugal. For media accreditation, please go to http://iff.multimeios.pt/index.php?option=com_wrapper&Itemid=45 A set of educational materials is also being prepared and will be finished in late April. To learn more about the show, please go to www.cosmicorigins.org

  15. Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

    PubMed Central

    Wang, Libo; Mei, Xiaohu; Atkinson, David; Small, Donald M.

    2014-01-01

    Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in lipid-free, lipid-poor, and lipid-bound states during lipid metabolism. To address the lipid binding and the dynamic desorption behavior of apoA-I at lipoprotein surfaces, apoA-I, Δ(185-243)apoA-I, and Δ(1-59)(185-243)apoA-I were studied at triolein/water and phosphatidylcholine/triolein/water interfaces with special attention to surface pressure. All three proteins are surface active to both interfaces lowering the interfacial tension and thus increasing the surface pressure to modify the interfaces. Δ(185-243)apoA-I adsorbs much more slowly and lowers the interfacial tension less than full-length apoA-I, confirming that the C-terminal domain (residues 185-243) initiates the lipid binding. Δ(1-59)(185-243)apoA-I binds more rapidly and lowers the interfacial tension more than Δ(185-243)apoA-I, suggesting that destabilizing the N-terminal α-helical bundle (residues 1-185) restores lipid binding. The three proteins desorb from both interfaces at different surface pressures revealing that different domains of apoA-I possess different lipid affinity. Δ(1-59)(185-243)apoA-I desorbs at lower pressures compared with apoA-I and Δ(185-243)apoA-I indicating that it is missing a strong lipid association motif. We propose that during lipoprotein remodeling, surface pressure mediates the adsorption and partial or full desorption of apoA-I allowing it to exchange among different lipoproteins and adopt various conformations to facilitate its multiple functions. PMID:24308948

  16. Severe Weather Research at the European Severe Storms Laboratory

    NASA Astrophysics Data System (ADS)

    Groenemeijer, Pieter

    2013-04-01

    The European Severe Storms Laboratory's (ESSL) aim is to increase understanding of high-impact weather, with a particular focus on phenomena with small spatial and temporal dimensions, such as large hail, convectively-driven severe wind gusts, tornadoes and extreme precipitation.The ESSL performs and supports research activities and contributes to enhancing forecasting and warning capabilities in several ways. First, ESSL supports research by providing quality-controlled point data on severe weather events in the European Severe Weather Database. These data are collected through collaborations with networks of voluntary observers, and National HydroMeteorological Institutes throughout Europe. Second, research carried out at ESSL includes modelling the present and future occurrence of severe weather phenomena. This is done by developing proxies for severe weather events for use with reanalysis and climate model data. Third, at the ESSL Testbed, new products to support forecasting and warning operations are tested and demonstrated. Among these tools are visualizations of NWP ensemble data as well as radar, satellite and lightning detection data. Testbed participants provide feedback to the products and receive training in forecasting severe convective weather. Last, every second year ESSL organizes or co-organizes the European Conferences on Severe Storms.

  17. A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia.

    PubMed

    Pisciotta, Livia; Fasano, Tommaso; Calabresi, Laura; Bellocchio, Antonella; Fresa, Raffaele; Borrini, Claudia; Calandra, Sebastiano; Bertolini, Stefano

    2008-05-01

    We report a large family in which four members showed a plasma lipid profile consistent with the clinical diagnosis of familial combined hyperlipidemia (FCHL). One of these patients was found to have markedly reduced HDL cholesterol (HDL-C) (0.72 mmol/l) and Apo A-I (72 mg/dl) levels, a condition suggestive of the presence of a mutation in one of the HDL-related genes. The analysis of APOA1 gene revealed that this patient was heterozygous for a cytosine insertion in exon 3 (c.49-50 ins C), resulting in a frame-shift and premature stop codon at position 26 of pro-Apo A-I (Q17PFsX10). This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband. Carriers of Apo A-I mutation had significantly lower HDL-C and Apo A-I than non-carriers family members (0.77+/-0.15 mmol/l vs. 1.15+/-0.20 mmol/l, P<0.005; 71.4+/-9.1mg/dl vs. 134.0+/-14.7 mg/dl, P<0.005, respectively). Two of the APOA1 mutation carriers, who were also heavy smokers, had fibrous plaques in the carotid arteries causing mild stenosis (20%). The intimal-media thickness in the two other adult carriers was within the normal range. The other non-carriers family members with FCHL had either overt vascular disease or carotid atherosclerosis at ultrasound examination. This observation suggests that the low HDL-C/low Apo A-I phenotype may result from a genetic defect directly affecting HDL metabolism, even in the context of a dyslipidemia which, like FCHL, is associated with low plasma HDL-C.

  18. Severe Hypokalemia Masquerading Myocardial Ischemia

    PubMed Central

    Petrov, Daniel Bogdanov; Sardovski, Svetlozar Ivanov; Milanova, Maria Hristova

    2012-01-01

    An advanced degree of body potassium deficit may produce striking changes in the electrocardiogram (ECG). These changes can result in incidental findings on the 12-lead ECG or precipitate potentially life-threatening dysrhythmias. Although usually readily recognized, at times these abnormalities may be confused with myocardial ischemia. The object was to report a case of severe hypokalemia mimicking myocardial ischemia. A 33-year-old, previously healthy man, presented to the Emergency Department (ED) with a progressive weakness and chest discomfort. The electrocardiogram showed a marked ST-segment depression in leads II, III, aVF, V1-V6. The initial diagnosis was non ST-elevation myocardial infarction. Echocardiography was normal and troponin levels were within normal limits. A more detailed history revealed that the patient had an episode of acute gastroenteritis with diarrhea and vomiting. Serum chemistries were notable for a potassium concentration of 1,8 mmol per liter. With aggressive electrolyte correction, the ECG abnormalities reverted as potassium levels normalized. Hypokalemia induced ST-segment depression may simulate myocardial ischemia. The differential diagnosis might be difficult, especially in the cases when ST changes are accompanied with chest discomfort.

  19. Severe Weather Forecast Decision Aid

    NASA Technical Reports Server (NTRS)

    Bauman, William H., III; Wheeler, Mark M.; Short, David A.

    2005-01-01

    This report presents a 15-year climatological study of severe weather events and related severe weather atmospheric parameters. Data sources included local forecast rules, archived sounding data, Cloud-to-Ground Lightning Surveillance System (CGLSS) data, surface and upper air maps, and two severe weather event databases covering east-central Florida. The local forecast rules were used to set threat assessment thresholds for stability parameters that were derived from the sounding data. The severe weather events databases were used to identify days with reported severe weather and the CGLSS data was used to differentiate between lightning and non-lightning days. These data sets provided the foundation for analyzing the stability parameters and synoptic patterns that were used to develop an objective tool to aid in forecasting severe weather events. The period of record for the analysis was May - September, 1989 - 2003. The results indicate that there are certain synoptic patterns more prevalent on days with severe weather and some of the stability parameters are better predictors of severe weather days based on locally tuned threat values. The results also revealed the stability parameters that did not display any skill related to severe weather days. An interactive web-based Severe Weather Decision Aid was developed to assist the duty forecaster by providing a level of objective guidance based on the analysis of the stability parameters, CGLSS data, and synoptic-scale dynamics. The tool will be tested and evaluated during the 2005 warm season.

  20. Nucleotide sequence and the encoded amino acids of human apolipoprotein A-I mRNA.

    PubMed Central

    Law, S W; Brewer, H B

    1984-01-01

    The cDNA clones encoding the precursor form of human liver apolipoprotein A-I (apoA-I), preproapoA-I, have been isolated from a cDNA library. A 17-base synthetic oligonucleotide based on residues 108-113 of apoA-I and a 26-base primer-extended, dideoxynucleotide-terminated cDNA were used as hybridization probes to select for recombinant plasmids bearing the apoA-I sequence. The complete nucleic acid sequence of human liver preproapoA-I has been determined by analysis of the cloned cDNA. The sequence is composed of 801 nucleotides encoding 267 amino acid residues. PreproapoA-I contains an 18-amino-acid prepeptide and a 6-amino-acid propeptide connected to the amino terminus of the 243-amino acid mature apoA-I. Southern blotting analysis of chromosomal DNA obtained from peripheral blood indicated the apoA-I gene is contained in a 2.1-kilobase-pair Pst I fragment and there is no gross difference in structural organization between the normal apoA-I gene and the Tangier disease apoA-I gene. Images PMID:6198645

  1. Risk factors for severe obstetric perineal lacerations.

    PubMed

    Vale de Castro Monteiro, Marilene; Pereira, Gláucia M Varella; Aguiar, Regina Amélia Pessoa; Azevedo, Rodrigo Leite; Correia-Junior, Mário Dias; Reis, Zilma Silveira Nogueira

    2016-01-01

    The aim of this study was to assess the occurrence of severe perineal lacerations in vaginal delivery and its relationship with predisposing clinical and obstetric factors. A retrospective cohort analysis using an electronic clinical database at a University Referral Center for high-risk pregnancies was performed. A total of 941 vaginal deliveries were analyzed, over 10 consecutive months in 2013 and 2014. The relationship between obstetric and clinical characteristics and lacerations, especially severe forms, was analyzed. The frequency and severity of birth canal lacerations were compiled and classified as mild (unintentional laceration grades I and II, and mediolateral episiotomy) and severe (grades III and IV). The crude and adjusted odds ratios and 95% confidence intervals were estimated in univariate and multivariate logistic regression models. The overall incidence of perineal lacerations in vaginal delivery was 78.2% (n = 731). Lacerations were considered mild in 708 women (75.7%) and severe in 23 women (2.5%). Maternal age, parity, use of forceps, mediolateral episiotomy, and birth weight influenced the occurrence of some degree of tear. The chance of severe lacerations increased 1.77-fold per week with the gestational age (1.03-3.03, P = 0.025), while primiparity increased the chance of laceration 5.32-fold. Episiotomy did not show a protective effect against severe laceration occurrence (P = 0.999). Severe perineal lacerations were associated with operative delivery, primiparity, gestational age, and epidural anesthesia. Episiotomy was not protective.

  2. A Systematic Investigation of Structure/Function Requirements for the Apolipoprotein A-I/Lecithin Cholesterol Acyltransferase Interaction Loop of High-density Lipoprotein.

    PubMed

    Gu, Xiaodong; Wu, Zhiping; Huang, Ying; Wagner, Matthew A; Baleanu-Gogonea, Camelia; Mehl, Ryan A; Buffa, Jennifer A; DiDonato, Anthony J; Hazen, Leah B; Fox, Paul L; Gogonea, Valentin; Parks, John S; DiDonato, Joseph A; Hazen, Stanley L

    2016-03-18

    The interaction of lecithin-cholesterol acyltransferase (LCAT) with apolipoprotein A-I (apoA-I) plays a critical role in high-density lipoprotein (HDL) maturation. We previously identified a highly solvent-exposed apoA-I loop domain (Leu(159)-Leu(170)) in nascent HDL, the so-called "solar flare" (SF) region, and proposed that it serves as an LCAT docking site (Wu, Z., Wagner, M. A., Zheng, L., Parks, J. S., Shy, J. M., 3rd, Smith, J. D., Gogonea, V., and Hazen, S. L. (2007) Nat. Struct. Mol. Biol. 14, 861-868). The stability and role of the SF domain of apoA-I in supporting HDL binding and activation of LCAT are debated. Here we show by site-directed mutagenesis that multiple residues within the SF region (Pro(165), Tyr(166), Ser(167), and Asp(168)) of apoA-I are critical for both LCAT binding to HDL and LCAT catalytic efficiency. The critical role for possible hydrogen bond interaction at apoA-I Tyr(166) was further supported using reconstituted HDL generated from apoA-I mutants (Tyr(166) → Glu or Asn), which showed preservation in both LCAT binding affinity and catalytic efficiency. Moreover, the in vivo functional significance of NO2-Tyr(166)-apoA-I, a specific post-translational modification on apoA-I that is abundant within human atherosclerotic plaque, was further investigated by using the recombinant protein generated from E. coli containing a mutated orthogonal tRNA synthetase/tRNACUA pair enabling site-specific insertion of the unnatural amino acid into apoA-I. NO2-Tyr(166)-apoA-I, after subcutaneous injection into hLCAT(Tg/Tg), apoA-I(-/-) mice, showed impaired LCAT activation in vivo, with significant reduction in HDL cholesteryl ester formation. The present results thus identify multiple structural features within the solvent-exposed SF region of apoA-I of nascent HDL essential for optimal LCAT binding and catalytic efficiency. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. A Method To Compare Rater Severity across Several Administrations.

    ERIC Educational Resources Information Center

    O'Neill, Thomas R.; Lunz, Mary E.

    This paper illustrates a method to study rater severity across exam administrations. A multi-facet Rasch model defined the ratings as being dominated by four facets: examinee ability, rater severity, project difficulty, and task difficulty. Ten years of data from administrations of a histotechnology performance assessment were pooled and analyzed…

  4. Statistics of Severe Tornadoes and Severe Tornado Outbreaks

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.; Turcotte, D. L.

    2012-04-01

    The standard measures of the intensity of a tornado in the USA and many other countries are the Fujita and Enhanced Fujita scales. These scales are based on the damage that a tornado causes. Another measure of the strength of a tornado is its path length of touchdown, L. In this study we consider 4,061 severe tornadoes (defined as L≥ 10 km) in the continental USA for the time period 1981-2010 (USA Storm Prediction Center Severe Weather Database). We find for individual severe tornadoes: (i) The noncumulative frequency-length statistics of severe tornado touchdown path lengths, 20 < L < 200 km, is well approximated by an inverse power-law relationship with exponent near 3. (ii) There is a strong linear scaling between the number of severe tornadoes in a year and their total path lengths in that year. We then take the total path length of severe tornadoes in a day, LD, as a measure of the strength of a 24-hour USA tornado outbreak. We find that: (i) On average, the number of days per year with at least one continental USA severe tornado (path length L≥ 10 km) has increased 16% in the 30-year period 1981-2010. (ii) The daily numbers of severe tornadoes in a USA outbreak have a strong power-law relationship (exponent 0.87) on their daily total path lengths, LD, over the range 20 < LD

  5. Statistical Scaling of Severe Tornadoes and Severe Tornado Outbreaks

    NASA Astrophysics Data System (ADS)

    Turcotte, D. L.; Malamud, B. D.

    2012-12-01

    The standard measures of the intensity of a tornado in the USA and many other countries are the Fujita and Enhanced Fujita scales. These scales are based on the damage that a tornado causes. Another measure of the strength of a tornado is its path length of touchdown, L. Here we consider severe tornadoes, which we define as L ≥ 10 km, in the continental USA (USA Storm Prediction Center Severe Weather Database). We find that for the period 1982-2011, for individual severe tornadoes (L ≥ 10 km): (i) There is a strong linear scaling between the number of severe tornadoes in a year and their total path lengths in that year. (ii) The cumulative path length data suggests that the longest severe tornado path length (or greater) expected in a year (on average) is L = 115 km and in a decade (on average) is L = 215 km. (iii) The noncumulative frequency-length statistics of severe tornado touchdown path lengths, 20 < L < 200 km, is well approximated by an inverse power-law relationship with exponent near 3. We then take the total path length of severe tornadoes in a convective day (12:00-12:00 UTC), LD, as a measure of the strength of a 24-hour USA tornado outbreak. We find that: (i) For 1982-2011, the numbers of severe tornadoes in a USA convective day outbreak have a strong power-law relationship (exponent 0.80) with their convective day total path lengths, LD, over the range 20 < LD < 1000 km/dy. (ii) For 1952-2011, the cumulative severe tornado outbreak path length data suggests that the longest daily outbreak path length total (or greater) expected in a year (on average) is LD = 480 km and in a decade (on average) is LD = 120 km. (iii) For 1982-2011, the noncumulative frequency-length statistics of tornado outbreaks, 10 < LD <1000 km/dy, is well approximated by an inverse power-law relationship with exponent near 1.8. Finally, we consider the frequency path-length scaling of severe tornadoes (L ≥ 10 km) during two tornado outbreaks, 27 April 2011 (67 severe

  6. Severity grading in radial dysplasia.

    PubMed

    Vilkki, S K

    2014-11-01

    A functional scoring method to grade the usefulness and quality of the upper limbs in congenital radial dysplasia is presented. It is based on the author's examinations of 44 arms with congenital deficiency of the radius. The hand (H), wrist (W) and proximal parts (P) of the extremity are each scored from 0 to 10 points for severity. The scoring is expressed similarly to the TNM (tumour, nodes, metastasis) tumour classification, for example as H5W4P2. The maximum severity index is 30 points. A severity grade of mild is between 1 and 8 points, moderate between 9 and 16 points and severe 17 points and over. In the author's series, the grades were mild in eight, moderate in 21 and severe in 15 cases. The functional severity grading should allow better comparison of radially deficient limbs and the results of treatment between groups of patients. © The Author(s) 2014.

  7. Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

    SciTech Connect

    Melchior, G.W.; Castle, C.K.

    1989-07-01

    Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD (apo A-I(50 kD)), whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range (apo A-I(LDL)). The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species.

  8. Statistics of severe tornadoes and severe tornado outbreaks

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.; Turcotte, D. L.

    2012-03-01

    The standard measures of the intensity of a tornado in the USA and many other countries are the Fujita and Enhanced Fujita scales. These scales are based on the damage that a tornado causes. Another measure of the strength of a tornado is its path length of touchdown, L. In this study we consider 4061 severe tornadoes (defined as L≥10 km) in the continental USA for the time period 1981-2010 (USA Storm Prediction Center Severe Weather Database). We find for individual severe tornadoes: (i) The noncumulative frequency-length statistics of severe tornado touchdown path lengths, 20 < L < 200 km, is well approximated by an inverse power-law relationship with exponent near 3. (ii) There is a strong linear scaling between the number of severe tornadoes in a year and their total path lengths in that year. We then take the total path length of severe tornadoes in a day, LD, as a measure of the strength of a 24-hour USA tornado outbreak. We find that: (i) On average, the number of days per year with at least one continental USA severe tornado (path length L≥10 km) has increased 16% in the 30-year period 1981-2010. (ii) The daily numbers of severe tornadoes in a USA outbreak have a strong power-law relationship (exponent 0.87) on their daily total path lengths, LD, over the range 20 < LD < 1000 km dy-1. (iii) The noncumulative frequency-length statistics of tornado outbreaks, 10 < LD < 1000 km dy-1, is well approximated by an inverse power-law relationship with exponent near 1.7. We believe that our robust scaling results provide evidence that touchdown path lengths can be used as quantitative measures of the systematic properties of severe tornadoes and severe tornado outbreaks.

  9. Statistics of Severe Tornadoes and Severe Tornado Outbreaks

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.; Turcotte, D. L.

    2011-12-01

    The standard measure of the intensity of a tornado in the USA and many other countries are the Fujita and Enhanced Fujita scales. These scales are based on the damage that a tornado causes. Another measure of the strength of a tornado is its path length of touchdown, L. In this study we consider 4,061 severe tornadoes, with L ≥ 10 km, in the continental USA for the period 1981-2010 (Storm Prediction Center Severe Weather Database). We find for individual severe tornadoes: (i) The noncumulative frequencies, f(L), have a strong power-law relationship on severe tornado path lengths, L. (ii) The dependence of the number of severe tornadoes in a year on the total length in that year also exhibits strong power-law scaling. We then take the total path length of severe tornadoes in a day, LD, as a measure of the strength of a 24-hour USA tornado outbreak. We find that: (i) The number of days on which USA outbreaks occur has increased 15% in the 30-year period considered over the continental USA. (ii) The numbers of severe tornadoes in a USA outbreak, ND, have a strong power-law relationship on total 24-hour path lengths, LD. (iii) The noncumulative frequencies, f(LD), have a strong power-law relationship on severe tornado path lengths, LD. We believe that our robust scaling results provide evidence that touchdown lengths might be used as quantitative measures of the systematic properties of severe tornadoes and severe tornado outbreaks.

  10. Indexes of severity: conceptual development.

    PubMed Central

    Krischer, J P

    1979-01-01

    A discussion of severity index development is presented in relation to conceptual issues in index definition, analytic issues in index formulation and validation issues in index application. The CHOP index is discussed along with six severity indexes described in an earlier paper dealing with underlying concepts to illustrate the material presented. Replies are provided to specific questions raised in an accompanying paper discussing the Injury Severity Score. This conceptual material is presented to provide a foundation for severity index development, to suggest criteria to be used in their formulation and testing, and to identify analyses that can lead to the successful selection and application of an index for a defined purpose. PMID:468553

  11. Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process

    PubMed Central

    Kim, Jae-Yong; Lee, Eun-Young; Park, Jin Kyun; Song, Yeong Wook; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2016-01-01

    Objective In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age. Methods We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13). Results Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC. The RA group showed significantly elevated levels of blood triglyceride (TG), uric acid, and cholesteryl ester transfer protein (CETP) activity. The RA group also showed elevated levels of advanced glycated end (AGE) products in all lipoproteins and severe aggregation of apoA-I in HDL. As CETP activity and TG contents were 2-fold increased in HDL from RA group, paraoxonase activity was reduced upto 20%. Electron microscopy revealed that RA group showed much less HDL2 particle number than control. LDL from the RA group was severely oxidized and glycated with greater fragmentation of apo-B, especially in female group, it was more atherogenic via phagocytosis. Conclusion Lipoproteins from the RA patients showed severely altered structure with impaired functionality, which is very similar to that observed in coronary heart patients. These dysfunctional properties in lipoproteins from the RA patients might be associated with high incidence of cardiovascular events in RA patients. PMID:27736980

  12. Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process.

    PubMed

    Kim, Jae-Yong; Lee, Eun-Young; Park, Jin Kyun; Song, Yeong Wook; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2016-01-01

    In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age. We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13). Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC. The RA group showed significantly elevated levels of blood triglyceride (TG), uric acid, and cholesteryl ester transfer protein (CETP) activity. The RA group also showed elevated levels of advanced glycated end (AGE) products in all lipoproteins and severe aggregation of apoA-I in HDL. As CETP activity and TG contents were 2-fold increased in HDL from RA group, paraoxonase activity was reduced upto 20%. Electron microscopy revealed that RA group showed much less HDL2 particle number than control. LDL from the RA group was severely oxidized and glycated with greater fragmentation of apo-B, especially in female group, it was more atherogenic via phagocytosis. Lipoproteins from the RA patients showed severely altered structure with impaired functionality, which is very similar to that observed in coronary heart patients. These dysfunctional properties in lipoproteins from the RA patients might be associated with high incidence of cardiovascular events in RA patients.

  13. Tetraparetic critically ill patients show electrophysiological signs of myopathy.

    PubMed

    Crone, Clarissa

    2017-09-01

    Critically ill patients often develop tetraparesis. It has been debated whether this is caused by neuropathy, myopathy, or both. The aim was to determine the incidence of myopathy and neuropathy in weak patients in the intensive care unit by performing several electrophysiological examinations, including quantitative electromyography (qEMG). Forty-nine patients referred for electrophysiological examination because of suspected critical illness-related weakness underwent qEMG, nerve conduction studies, and direct muscle stimulation. The qEMG showed signs of myopathy in 33 of 35 patients. Direct muscle stimulation was consistent with myopathy in 31 of 34 patients. Amplitudes of compound muscle action potentials were decreased in all patients. Four patients also had signs of sensory neuropathy, which could not be explained by preexisting medical conditions. When combined, the results are compatible with muscle dysfunction in all patients. This will help to direct future studies of the pathophysiology of this serious condition. Muscle Nerve 56: 433-440, 2017. © 2016 Wiley Periodicals, Inc.

  14. RISK and SAFE Signaling Pathway Involvement in Apolipoprotein A-I-Induced Cardioprotection

    PubMed Central

    Kalakech, Hussein; Hibert, Pierre; Prunier-Mirebeau, Delphine; Tamareille, Sophie; Letournel, Franck; Macchi, Laurent; Pinet, Florence; Furber, Alain; Prunier, Fabrice

    2014-01-01

    Recent findings indicate that apolipoprotein A-I (ApoA-I) may be a protective humoral mediator involved in remote ischemic preconditioning (RIPC). This study sought to determine if ApoA-I mediates its protective effects via the RISK and SAFE signaling pathways implicated in RIPC. Wistar rats were allocated to one of the following groups. Control: rats were subjected to myocardial ischemia/reperfusion (I/R) without any further intervention; RIPC: four cycles of limb I/R were applied prior to myocardial ischemia; ApoA-I: 10 mg/Kg of ApoA-I were intravenously injected prior to myocardial ischemia; ApoA-I + inhibitor: pharmacological inhibitors of RISK/SAFE pro-survival kinase (Akt, ERK1/2 and STAT-3) were administered prior to ApoA-I injection. Infarct size was significantly reduced in the RIPC group compared to Control. Similarly, ApoA-I injection efficiently protected the heart, recapitulating RIPC-induced cardioprotection. The ApoA-I protective effect was associated with Akt and GSK-3β phosphorylation and substantially inhibited by pretreatment with Akt and ERK1/2 inhibitors. Pretreatment with ApoA-I in a rat model of I/R recapitulates RIPC-induced cardioprotection and shares some similar molecular mechanisms with those of RIPC-involved protection of the heart. PMID:25237809

  15. Inhibition of apolipoprotein A-I gene expression by obesity-associated endocannabinoids.

    PubMed

    Haas, Michael J; Mazza, Angela D; Wong, Norman C W; Mooradian, Arshag D

    2012-04-01

    Obesity is associated with increased serum endocannabinoid (EC) levels and decreased high-density lipoprotein cholesterol (HDLc). Apolipoprotein A-I (apo A-I), the primary protein component of HDL is expressed primarily in the liver and small intestine. To determine whether ECs regulate apo A-I gene expression directly, the effect of the obesity-associated ECs anandamide and 2-arachidonylglycerol on apo A-I gene expression was examined in the hepatocyte cell line HepG2 and the intestinal cell line Caco-2. Apo A-I protein secretion was suppressed nearly 50% by anandamide and 2-arachidonoylglycerol in a dose-dependent manner in both cell lines. Anandamide treatment suppressed both apo A-I mRNA and apo A-I gene promoter activity in both cell lines. Studies using apo A-I promoter deletion constructs indicated that repression of apo A-I promoter activity by anandamide requires a previously identified nuclear receptor binding site designated as site A. Furthermore, anandamide-treatment inhibited protein-DNA complex formation with the site A probe. Exogenous over expression of cannabinoid receptor 1 (CBR1) in HepG2 cells suppressed apo A-I promoter activity, while in Caco-2 cells, exogenous expression of both CBR1 and CBR2 could repress apo A-I promoter activity. The suppressive effect of anandamide on apo A-I promoter activity in Hep G2 cells could be inhibited by CBR1 antagonist AM251 but not by AM630, a selective and potent CBR2 inhibitor. These results indicate that ECs directly suppress apo A-I gene expression in both hepatocytes and intestinal cells, contributing to the decrease in serum HDLc in obese individuals.

  16. Severe hyponatremia and Schmidt's syndrome.

    PubMed

    Wehbe, Edgard; Grant, Michael E

    2008-06-01

    Severe hyponatremia, defined by a sodium concentration of below 115 meq/l, is rarely reported with Schmidt's syndrome. We report a 43-year-old woman diagnosed with Schmidt's syndrome during the workup for severe hyponatremia as well a review of all the reported cases. The Medline database from 1960 to 2007 and relevant references of selected articles were searched. Search terms included hyponatremia, hypothyroidism, autoimmune thyroid disease, adrenal insufficiency, adrenal failure, Schmidt's syndrome and autoimmune polyendocrine syndrome type 2. The search was restricted to the English language, human subjects, and patients with a serum sodium concentration of below 115 meq/l. Seven cases were reported including this report. Severe hyponatremia seems to be found more often in patients with severe hypothyroidism. To our knowledge this is the first case to describe the occurrence of severe hyponatremia with normal thyroid function test and normal baseline cortisol level.

  17. Current treatment of severe asthma.

    PubMed

    Hashimoto, S; Bel, E H

    2012-05-01

    Severe asthma is considered a heterogeneous disease in which a variety of clinical, physiological and inflammatory markers determine disease severity. Pivotal studies in the last 5 years have led to substantial progress in many areas, ranging from a more accurate definition of truly severe, refractory asthma, to classification of the disease into distinct clinical phenotypes, and introduction of new therapies. This review focuses on three common clinical phenotypes of severe asthma in adults (early onset severe allergic asthma, late onset non-atopic eosinophilic asthma, late onset non-eosinophilic asthma with obesity), and provides an overview of recent developments regarding treatment options that are best suited for each of these phenotypes. © 2012 Blackwell Publishing Ltd.

  18. Map Showing Lava Inundation Zones for Mauna Loa, Hawaii

    USGS Publications Warehouse

    Trusdell, F.A.; Graves, P.; Tincher, C.R.

    2002-01-01

    Introduction The Island of Hawaii is composed of five coalesced basaltic volcanoes. Lava flows constitute the greatest volcanic hazard from these volcanoes. This report is concerned with lava flow hazards on Mauna Loa, the largest of the island shield volcanoes. Hilo lies 58 km from the summit of Mauna Loa, the Kona coast 33 km, and the southernmost point of the island 61 km. Hawaiian volcanoes erupt two morphologically distinct types of lava, aa and pahoehoe. The surfaces of pahoehoe flows are rather smooth and undulating. Pahoehoe flows are commonly fed by lava tubes, which are well insulated, lava-filled conduits contained within the flows. The surfaces of aa flows are extremely rough and composed of lava fragments. Aa flows usually form lava channels rather than lava tubes. In Hawaii, lava flows are known to reach distances of 50 km or more. The flows usually advance slowly enough that people can escape from their paths. Anything overwhelmed by a flow will be damaged or destroyed by burial, crushing, or ignition. Mauna Loa makes up 51 percent of the surface area of the Island of Hawaii. Geologic mapping shows that lava flows have covered more than 40 percent of the surface every 1,000 years. Since written descriptions of its activity began in A.D. 1832, Mauna Loa has erupted 33 times. Some eruptions begin with only brief seismic unrest, whereas others start several months to a year following increased seismic activity. Once underway, the eruptions can produce lava flows that reach the sea in less than 24 hours, severing roads and utilities. For example, the 1950 flows from the southwest rift zone reached the ocean in approximately three hours. The two longest flows of Mauna Loa are pahoehoe flows from the 50-kilometer-long 1859 and the 48-kilometer-long 1880-81 eruptions. Mauna Loa will undoubtedly erupt again. When it does, the first critical question that must be answered is: Which areas are threatened with inundation? Once the threatened areas are

  19. Impact of pavement conditions on crash severity.

    PubMed

    Li, Yingfeng; Liu, Chunxiao; Ding, Liang

    2013-10-01

    Pavement condition has been known as a key factor related to ride quality, but it is less clear how exactly pavement conditions are related to traffic crashes. The researchers used Geographic Information System (GIS) to link Texas Department of Transportation (TxDOT) Crash Record Information System (CRIS) data and Pavement Management Information System (PMIS) data, which provided an opportunity to examine the impact of pavement conditions on traffic crashes in depth. The study analyzed the correlation between several key pavement condition ratings or scores and crash severity based on a large number of crashes in Texas between 2008 and 2009. The results in general suggested that poor pavement condition scores and ratings were associated with proportionally more severe crashes, but very poor pavement conditions were actually associated with less severe crashes. Very good pavement conditions might induce speeding behaviors and therefore could have caused more severe crashes, especially on non-freeway arterials and during favorable driving conditions. In addition, the results showed that the effects of pavement conditions on crash severity were more evident for passenger vehicles than for commercial vehicles. These results provide insights on how pavement conditions may have contributed to crashes, which may be valuable for safety improvement during pavement design and maintenance. Readers should notice that, although the study found statistically significant effects of pavement variables on crash severity, the effects were rather minor in reality as suggested by frequency analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Human apolipoprotein A-I exerts a prophylactic effect on high-fat diet-induced atherosclerosis via inflammation inhibition in a rabbit model.

    PubMed

    Li, Jiyang; Wang, Weina; Han, Lei; Feng, Meiqing; Lu, Hui; Yang, Li; Hu, Xiangxiang; Shi, Si; Jiang, Shanshan; Wang, Qian; Ye, Li

    2017-02-06

    Apolipoprotein A-I (apoA-I) is the major functional protein fraction of high-density lipoprotein. The prophylactic effect and mechanism of human apoA-I on atherosclerosis (AS) were investigated in a high-fat diet-induced AS rabbit model. The rabbits were injected with apoA-I once a week while fed high-fat diet for 20 weeks. Our results showed that apoA-I could raise the serum level of high-density lipoprotein-cholesterol and reduce those of lipid total cholesterol, triglyceride, and low-density lipoprotein-cholesterol in AS rabbits. Decreased aortic plaque area and aortic injury degree were also observed by Oil Red O staining and HE staining in apoA-I-treated high-fat diet-induced AS rabbits. Further study elucidated that apoA-I could down-regulate the expression of some inflammatory mediators including intercellular adhesion molecule type 1, vascular adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-6 (IL-6), and C-reactive protein in serum and aorta of AS rabbits. In addition, real-time quantitative RT-PCR analyses showed that the apoA-I infusions decreased the mRNA levels of two pro-inflammatory molecules, i.e. nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), in aorta of AS rabbits, which was associated with a concomitant reduction in endothelial VCAM-1 and IL-6 mRNA transcription. Together, our results support the atheroprotective and prophylactic role of apoA-I in vivo, and this activity may be correlated with its anti-inflammatory effect. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. A Systematic Investigation of Structure/Function Requirements for the Apolipoprotein A-I/Lecithin Cholesterol Acyltransferase Interaction Loop of High-density Lipoprotein*

    PubMed Central

    Gu, Xiaodong; Wu, Zhiping; Huang, Ying; Wagner, Matthew A.; Baleanu-Gogonea, Camelia; Mehl, Ryan A.; Buffa, Jennifer A.; DiDonato, Anthony J.; Hazen, Leah B.; Fox, Paul L.; Gogonea, Valentin; Parks, John S.; DiDonato, Joseph A.; Hazen, Stanley L.

    2016-01-01

    The interaction of lecithin-cholesterol acyltransferase (LCAT) with apolipoprotein A-I (apoA-I) plays a critical role in high-density lipoprotein (HDL) maturation. We previously identified a highly solvent-exposed apoA-I loop domain (Leu159–Leu170) in nascent HDL, the so-called “solar flare” (SF) region, and proposed that it serves as an LCAT docking site (Wu, Z., Wagner, M. A., Zheng, L., Parks, J. S., Shy, J. M., 3rd, Smith, J. D., Gogonea, V., and Hazen, S. L. (2007) Nat. Struct. Mol. Biol. 14, 861–868). The stability and role of the SF domain of apoA-I in supporting HDL binding and activation of LCAT are debated. Here we show by site-directed mutagenesis that multiple residues within the SF region (Pro165, Tyr166, Ser167, and Asp168) of apoA-I are critical for both LCAT binding to HDL and LCAT catalytic efficiency. The critical role for possible hydrogen bond interaction at apoA-I Tyr166 was further supported using reconstituted HDL generated from apoA-I mutants (Tyr166 → Glu or Asn), which showed preservation in both LCAT binding affinity and catalytic efficiency. Moreover, the in vivo functional significance of NO2-Tyr166-apoA-I, a specific post-translational modification on apoA-I that is abundant within human atherosclerotic plaque, was further investigated by using the recombinant protein generated from E. coli containing a mutated orthogonal tRNA synthetase/tRNACUA pair enabling site-specific insertion of the unnatural amino acid into apoA-I. NO2-Tyr166-apoA-I, after subcutaneous injection into hLCATTg/Tg, apoA-I−/− mice, showed impaired LCAT activation in vivo, with significant reduction in HDL cholesteryl ester formation. The present results thus identify multiple structural features within the solvent-exposed SF region of apoA-I of nascent HDL essential for optimal LCAT binding and catalytic efficiency. PMID:26797122

  2. Abnormal movements associated with severe hyponatraemia.

    PubMed Central

    Nagaratnam, N.; Icao, E.; Peric, H.

    1997-01-01

    An elderly woman with severe hyponatraemia manifested transient choreoathetoid movements of the upper extremities and dyskinetic movements of the face and mouth. She showed more than one type of hyponatraemia and a precise diagnosis was not possible. The movements were abolished with treatment of the hyponatraemia with no recurrence or sequelae. PMID:9307743

  3. Abnormal movements associated with severe hyponatraemia.

    PubMed

    Nagaratnam, N; Icao, E; Peric, H

    1997-08-01

    An elderly woman with severe hyponatraemia manifested transient choreoathetoid movements of the upper extremities and dyskinetic movements of the face and mouth. She showed more than one type of hyponatraemia and a precise diagnosis was not possible. The movements were abolished with treatment of the hyponatraemia with no recurrence or sequelae.

  4. Measuring Severity and Change in Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Piazza, Eugene; And Others

    1983-01-01

    Describes the State of Mind (SOM) Questionnaire, which measures severity and change of clinical state in anorexia nervosa. A study of 42 anorexia patients and 4 control groups showed a strong correlation between depression as measured by the Beck Depression Inventory and the Anorexia Scale, which comprise the SOM. (JAC)

  5. Measuring Severity and Change in Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Piazza, Eugene; And Others

    1983-01-01

    Describes the State of Mind (SOM) Questionnaire, which measures severity and change of clinical state in anorexia nervosa. A study of 42 anorexia patients and 4 control groups showed a strong correlation between depression as measured by the Beck Depression Inventory and the Anorexia Scale, which comprise the SOM. (JAC)

  6. National Severe Storms Forecast Center

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The principal mission of the National Severe Storms Forecast Center (NSSFC) is to maintain a continuous watch of weather developments that are capable of producing severe local storms, including tornadoes, and to prepare and issue messages designated as either Weather Outlooks or Tornado or Severe Thunderstorm Watches for dissemination to the public and aviation services. In addition to its assigned responsibility at the national level, the NSSFC is involved in a number of programs at the regional and local levels. Subsequent subsections and paragraphs describe the NSSFC, its users, inputs, outputs, interfaces, capabilities, workload, problem areas, and future plans in more detail.

  7. Who pays the severance tax

    SciTech Connect

    Weinstein, B.L.

    1984-03-01

    Over the past four years, taxes levied by states on energy production have become a source of contention between the ''energy have'' and ''energy have-not'' regions of the nation. The popular notion that the taxes are shifted forward to consumers has gone virtually unchallenged in the policy debate. This paper examines the incidence and burden of severance taxes and also assesses the impact of severance taxation on production, investment, and land use. The author concludes that severance taxes are not shifted forward to consumers but are borne by producers and resources owners in the form of reduced profits and rents. 5 references.

  8. Fracture/Severance of Materials

    NASA Technical Reports Server (NTRS)

    Schimmel, Morry L. (Inventor); Bement, Laurence J. (Inventor); DuBrucq, Glenn F., Jr. (Inventor); Klein, Edward A. (Inventor)

    1998-01-01

    A method for severing or weakening materials is discussed. Explosive cords are placed in grooves on the upper surface of the material to be severed or weakened. The explosive cords are initiated simultaneously to introduce explosive shock waves into the material. These shock waves progress toward the centerline between the explosive cords and the lower surface of the material. Intersecting and reflected waves produce a rarefaction zone on the centerline to fail the material in tension. A groove may also be cut in the lower surface of the material to aid in severing or weakening the material.

  9. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  10. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  11. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  12. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  13. 22 CFR 204.22 - Right of A.I.D. to cure default.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Right of A.I.D. to cure default. 204.22 Section... CONDITIONS Procedure for Obtaining Compensation § 204.22 Right of A.I.D. to cure default. Within sixty (60) days after the Date of Application for Compensation, A.I.D. may at any time make payments to the Lender...

  14. Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same

    DOEpatents

    Oda, Michael N.; Forte, Trudy M.

    2007-05-29

    Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

  15. Induction of apolipoprotein A-I gene expression by black seed (Nigella sativa) extracts.

    PubMed

    Haas, Michael J; Onstead-Haas, Luisa M; Naem, Emad; Wong, Norman C W; Mooradian, Arshag D

    2014-09-01

    Black seed [Nigella sativa L. (Ranunculaceae)] has been shown in animal models to lower serum cholesterol levels. In order to determine if extracts from black seed have any effects on high-density lipoprotein (HDL), we characterized the effects of black seed extract on apolipoprotein A-I (apo A-I) gene expression, the primary protein component of HDL. Hepatocytes (HepG2) and intestinal cells (Caco-2) were treated with black seed extracts, and Apo A-I, peroxisome proliferator-activated receptor α (PPARα), and retinoid-x-receptor α (RXRα) were measured by Western blot analysis. Apo A-I mRNA levels were measured by quantitative real-time polymerase chain reaction and apo A-I gene transcription was measured by transient transfection of apo A-I reporter plasmids. Extracts from black seeds significantly increased hepatic and intestinal apo A-I secretion, as well as apo A-I mRNA and gene promoter activity. This effect required a PPARα binding site in the apo A-I gene promoter. Treatment of the extract with either heat or trypsin had no effect on its ability to induce apo A-I secretion. Treatment with black seed extract induced PPARα expression 9-fold and RXRα expression 2.5-fold. Furthermore, the addition of PPARα siRNA but not a control siRNA prevented some but not all the positive effects of black seed on apo A-I secretion. Black seed extract is a potent inducer of apo A-I gene expression, presumably by enhancing PPARα/RXRα expression. We conclude that black seed may have beneficial effects in treating dyslipidemia and coronary heart disease.

  16. The unsolved mystery of apoA-I recycling in adipocyte.

    PubMed

    Wang, Shuai; Peng, Dao-quan; Yi, Yuhong

    2016-02-24

    As the major storage site for triglycerides and free cholesterol, adipose tissue plays a central role in energy metabolism. ApoA-I is the main constituent of HDL and plays an important role in removal of excess cholesterol from peripheral tissues. Recently, multiple studies have shown beneficial effects of apoA-I on adipose metabolism and function. ApoA-I was reported to improve insulin sensitivity and exert anti-inflammatory, anti-obesity effect in animal studies. Interestingly, Uptake and resecretion of apoA-I by adipocytes has been detected. However, the significance of apoA-I recycling by adipocytes is still not clear. This article reviewed methods used to study cellular recycling of apoA-I and summarized the current knowledge on the mechanisms involved in apoA-I uptake by adipocytes. Since the main function of apoA-I is to mediate reverse cholesterol transport from peripheral tissues, the role of apoA-I internalization and re-secretion by adipocytes in intracellular cholesterol transport under physiological and pathological conditions were discussed. In addition, findings on the correlation between apoA-I recycling and obesity were discussed. Finally, it was proposed that during intracellular transport, apoA-I-protein complex may acquire cargoes other than lipids and deliver regulatory information when they were resecreted into the plasma. Although apoA-I recycling by adipocytes is still an unsolved mystery, it's likely that it is more than a redundant pathway especially under pathological conditions.

  17. Diabetic foot disease: grading inflammation by apolipoprotein A-I, C-reactive protein and serum amyloid A.

    PubMed

    Wang, Weiling; Zhang, Yan; Liao, Yonggan; Wu, Jun; Zhou, Lixia; Tang, Yijun; Cao, Yang; Metzmann, Erwin; Wang, Rongfang

    2014-01-01

    The different grading systems for diabetic foot disease pose a challenge in clinical decision making because each system fails to accurately reflect the individual course of disease progression. This study attempts to identify laboratory measurements for classifying diabetic foot disease to guide clinical treatment. The sera of 111 clinically graded diabetic foot patients were measured for several laboratory parameters including serum amyloid A (SAA), C-reactive protein (CRP), and apo A-I. By using the molar sum of CRP and SAA and then dividing by the molarity of apo A-I, an acute phase index was introduced to assess the inflammatory status of the patients. Based on a newly defined acute phase index (API), diabetic foot patients were classified into 3 distinct groups that provide a diagnostic tool complementing the established Texas grading system for clinical decision making. The integration of the serum concentrations of SAA, CRP and apo A-I into an acute phase index (API) offers an opportunity to triage diabetic foot patients who may benefit from personalized medicine.

  18. Dust Storm Time Lapse Shows Opportunity's Skies Darken

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] Dust Storm Time Lapse Shows Opportunity's Skies Darken

    NASA's Opportunity rover is literally seeing some of its darkest days. Both Mars Exploration Rovers have been riding out a regional dust storm for several weeks. Conditions became particularly dreary in the Meridiani Planum region where Opportunity sits, perched on the edge of 'Victoria Crater.'

    This image is a time-lapse composite where each horizon-survey image has been compressed horizontally (but not vertically) to emphasize the sky. The relative brightness and darkness of the sky from sol to sol (over a 30-sol period beginning June 14, 2007) is depicted accurately in these images, which view roughly the same part of the plains southwest of the rover. The images are approximately true color composites, generated from calibrated radiance data files using the panoramic camera's 601-nanometer, 535-nanometer and 482-nanometer filters.

    The rovers' atmospheric science team is concerned that smaller, regional dust storms could expand into a larger, globe-encircling storm. That could extend the time the sun stays obscured, challenging the capability of Opportunity's solar panels to produce enough electricity for the rover to function.

    Fortunately, as of July 19, 2007, the Opportunity site is clearing slightly. When the storm ends, atmospheric scientists hope to review data from the rovers that will help them determine what sort of dust was being lifted and distributed.

    The numbers across the top of the image report a measurement of atmospheric opacity, called by the Greek letter tau. The lower the number, the clearer the sky. Both Opportunity and Spirit have been recording higher tau measurements in July 2007 than they had seen any time previously in their three and a half years on Mars. The five sol numbers across the bottom correspond (left to right) to June 14, June 30, July 5, July 13 and July 15, 2007.

  19. Curcumin shows excellent therapeutic effect on psoriasis in mouse model.

    PubMed

    Kang, Di; Li, Bowen; Luo, Lei; Jiang, Wenbing; Lu, Qiumin; Rong, Mingqing; Lai, Ren

    2016-04-01

    Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis.

  20. Dust Storm Time Lapse Shows Opportunity's Skies Darken

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] Dust Storm Time Lapse Shows Opportunity's Skies Darken

    NASA's Opportunity rover is literally seeing some of its darkest days. Both Mars Exploration Rovers have been riding out a regional dust storm for several weeks. Conditions became particularly dreary in the Meridiani Planum region where Opportunity sits, perched on the edge of 'Victoria Crater.'

    This image is a time-lapse composite where each horizon-survey image has been compressed horizontally (but not vertically) to emphasize the sky. The relative brightness and darkness of the sky from sol to sol (over a 30-sol period beginning June 14, 2007) is depicted accurately in these images, which view roughly the same part of the plains southwest of the rover. The images are approximately true color composites, generated from calibrated radiance data files using the panoramic camera's 601-nanometer, 535-nanometer and 482-nanometer filters.

    The rovers' atmospheric science team is concerned that smaller, regional dust storms could expand into a larger, globe-encircling storm. That could extend the time the sun stays obscured, challenging the capability of Opportunity's solar panels to produce enough electricity for the rover to function.

    Fortunately, as of July 19, 2007, the Opportunity site is clearing slightly. When the storm ends, atmospheric scientists hope to review data from the rovers that will help them determine what sort of dust was being lifted and distributed.

    The numbers across the top of the image report a measurement of atmospheric opacity, called by the Greek letter tau. The lower the number, the clearer the sky. Both Opportunity and Spirit have been recording higher tau measurements in July 2007 than they had seen any time previously in their three and a half years on Mars. The five sol numbers across the bottom correspond (left to right) to June 14, June 30, July 5, July 13 and July 15, 2007.

  1. The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, Apolipoprotein B, Apolipoprotein A-I and Malondialdehyde in Type 2 Diabetic Patients

    PubMed Central

    Khandouzi, Nafiseh; Shidfar, Farzad; Rajab, Asadollah; Rahideh, Tayebeh; Hosseini, Payam; Mir Taheri, Mohsen

    2015-01-01

    Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro- and macro-vascular diseases. Anti-diabetic, hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate the effects of ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical trial, a total of 41 type 2 diabetic patients randomly were assigned to ginger or placebo groups (22 in ginger group and 19 in control group), received 2 g/day of ginger powder supplement or lactose as placebo for 12 weeks. The serum concentrations of fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I and malondialdehyde were analyzed before and after the intervention. Ginger supplementation significantly reduced the levels of fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein B/apolipoprotein A-I and malondialdehyde in ginger group in comparison to baseline, as well as control group, while it increased the level of apolipoprotein A-I (p<0.05). It seems that oral administration of ginger powder supplement can improves fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, apolipoprotein B/apolipoprotein A-I and malondialdehyde in type 2 diabetic patients. So it may have a role in alleviating the risk of some chronic complications of diabetes. PMID:25561919

  2. The effects of ginger on fasting blood sugar, hemoglobin a1c, apolipoprotein B, apolipoprotein a-I and malondialdehyde in type 2 diabetic patients.

    PubMed

    Khandouzi, Nafiseh; Shidfar, Farzad; Rajab, Asadollah; Rahideh, Tayebeh; Hosseini, Payam; Mir Taheri, Mohsen

    2015-01-01

    Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro- and macro-vascular diseases. Anti-diabetic, hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate the effects of ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical trial, a total of 41 type 2 diabetic patients randomly were assigned to ginger or placebo groups (22 in ginger group and 19 in control group), received 2 g/day of ginger powder supplement or lactose as placebo for 12 weeks. The serum concentrations of fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I and malondialdehyde were analyzed before and after the intervention. Ginger supplementation significantly reduced the levels of fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein B/apolipoprotein A-I and malondialdehyde in ginger group in comparison to baseline, as well as control group, while it increased the level of apolipoprotein A-I (p<0.05). It seems that oral administration of ginger powder supplement can improves fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, apolipoprotein B/apolipoprotein A-I and malondialdehyde in type 2 diabetic patients. So it may have a role in alleviating the risk of some chronic complications of diabetes.

  3. Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis

    PubMed Central

    Trocmé, Candice; Marotte, Hubert; Baillet, Athan; Pallot-Prades, Béatrice; Garin, Jérome; Grange, Laurent; Miossec, Pierre; Tebib, Jacques; Berger, François; Nissen, Michael J.; Juvin, Robert; Morel, Françoise; Gaudin, Philippe

    2009-01-01

    Objectives The use of biologics such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. Methods Plasma profiles of 60 RA patients (28 non-responders ACR 20 negative and 32 responders ACR 70 positive to infliximab) were studied by SELDI-TOF-MS technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterization was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by MALDI-TOF analysis. Results Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity > 56%, specificity > 77.5%). Moreover combination of several biomarkers improved both the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterized as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. Conclusions We characterized six plasma biomarkers, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders. PMID:18664547

  4. Astronomers Make "Movie" of Radio Images Showing Supernova Explosion

    NASA Astrophysics Data System (ADS)

    1995-11-01

    - dispersed radio telescopes has existed for only a few years. Supernova 1993J was the first one that was both close enough and had radio emission strong enough to enable scientists to make such detailed images. While the circular images show that the explosion debris is expanding symmetrically, the radio emission is stronger on one side of the shell. The explanation for this is unclear. Some astronomers have suggested that the stronger emission could result from the debris interacting with a companion star orbiting the one that exploded. The researchers believe that their sequence of images, with the stronger emission persisting for months after the explosion, makes the companion-star hypothesis unlikely. Previous radio observations of older and larger supernova shells have revealed protrusions within the shell. The latest images, however, show no such protrusions. This places limits on theories of how the protrusions form. In addition, the new images show that Supernova 1993J's debris shell has shown no signs yet of slowing due to interaction with material surrounding it. The material from the star's explosion is moving at nearly 10,000 miles per second, according to the researchers. At that speed, the material would travel the distance from the Earth to Saturn in one day. When the angular expansion rate of the supernova debris measured by the radio observatories is combined with the expansion speed of the same debris, measured by optical astronomers, it is possible to obtain an accurate value of the distance to M81. The value determined, 11 million light-years, is similar to that obtained by other, independent, means. This is important, as astronomers continue to seek more accurate distances to celestial objects to better gauge the actual size of the Universe. In addition to the VLA and several antennas of the VLBA, the scientists used German and Italian radio telescopes, as well as NASA facilities in California and Spain.

  5. Properties of discoidal complexes of human apolipoprotein A-I with phosphatidylcholines containing various fatty acid chains.

    PubMed

    Zorich, N L; Kézdy, K E; Jonas, A

    1987-06-02

    In this study we demonstrate that apolipoprotein A-I determined the common size classes of discoidal particles formed with numerous phosphatidylcholines, and with ether analogs of phosphatidylcholines. We show furthermore, that the nature of the lipids dictates the distribution of particles among the different size classes. These experiments were performed with discoidal complexes containing various phospholipids (phosphatidylcholines with saturated and unsaturated fatty acid chains of different lengths and the ether analog of 1-palmitoyl-2-oleoylphosphatidylcholine), cholesterol, and human apolipoprotein A-I, prepared by the sodium cholate dialysis method, and fractionated by Bio-Gel A-5m gel-filtration chromatography. The complex preparations were analyzed in terms of their average composition, spectral properties of the apolipoprotein, and the dynamic behavior of the lipid domains. Nondenaturing gradient gel electrophoresis was used to analyze the size classes of particles present in the complex preparations. Starting with reaction mixtures containing around 100:1, phospholipid/apolipoprotein A-I molar ratios, complexes were isolated with molar ratios from 40:1 to 100:1. In most complexes apolipoprotein A-I had high levels of alpha-helical structure (65-77% alpha-helix), and tryptophan residues in a nonpolar environment. The lipid domains of complexes exhibited the dynamic behavior expected of the main phospholipid components. In the average size range from 90 to 100 A diameters, discrete particle classes with 80, 87, 102, 108, or 112 A Stokes diameters were observed for all the complexes containing different phospholipids. These discrete, recurring particle sizes are attributed to distinct apolipoprotein A-I conformations and variable lipid content.

  6. Role of urea on recombinant Apo A-I stability and its utilization in anion exchange chromatography.

    PubMed

    Angarita, Monica; Arosio, Paolo; Müller-Späth, Thomas; Baur, Daniel; Falkenstein, Roberto; Kuhne, Wolfgang; Morbidelli, Massimo

    2014-08-08

    Apolipoprotein A-I (Apo A-I) is an important lipid-binding protein involved in the transport and metabolism of cholesterol. High protein purity, in particular with respect to endotoxins is required for therapeutic applications. The use of urea during the purification process of recombinant Apo A-I produced in Escherichia coli has been suggested so as to provide high endotoxin clearance. In this work, we show that urea can be used as a sole modifier during the ion exchange chromatographic purification of Apo A-I and we investigate the molecular mechanism of elution by correlating the effect of urea on self-association, conformation and adsorption equilibrium properties of a modified model Apo A-I. In the absence of urea the protein was found to be present as a population of oligomers represented mainly by trimers, hexamers and nonamers. The addition of urea induced oligomer dissociation and protein structure unfolding. We correlated the changes in protein association and conformation with variations of the adsorption equilibrium of the protein on a strong anion exchanger. It was confirmed that the adsorption isotherms, described by a Langmuir model, were dependent on both protein and urea concentrations. Monomers, observed at low urea concentration (0.5M), were characterized by larger binding affinity and adsorption capacity compared to both protein oligomers (0M) and unfolded monomers (2-8M). The reduction of both the binding strength and maximum adsorption capacity at urea concentrations larger than 0.5M explains the ability of urea of inducing elution of the protein from the ion exchange resin. The dissociation of the protein complexes occurring during the elution could likely be the origin of the effective clearance of endotoxins originally trapped inside the oligomers.

  7. Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I.

    PubMed

    Chan, Gary K L; Witkowski, Andrzej; Gantz, Donald L; Zhang, Tianqi O; Zanni, Martin T; Jayaraman, Shobini; Cavigiolio, Giorgio

    2015-04-24

    High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Isolation and function analysis of apolipoprotein A-I gene response to virus infection in grouper.

    PubMed

    Wei, Jingguang; Gao, Pin; Zhang, Ping; Guo, Minglan; Xu, Meng; Wei, Shina; Yan, Yang; Qin, Qiwei

    2015-04-01

    Apolipoproteins, synthesized mainly in liver and intestine and bounded to lipids, play important roles in lipid transport and uptake through the circulation system. In this study, an apolipoprotein A-I gene homologue was cloned from orange-spotted grouper Epinephelus coioides (designed as Ec-ApoA-I) by rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA of Ec-ApoA-I was comprised of 1278 bp with a 792 bp open reading frame (ORF) that encodes a putative protein of 264 amino acids. Quantitative real-time PCR (qPCR) analysis revealed that Ec-ApoA-I was abundant in liver and intestine, and the expression in liver was significantly (P < 0.01) up-regulated after the stimulation of LPS, Poly(I:C), Vibrio alginolyticus, and Singapore grouper iridovirus (SGIV). Recombinant Ec-ApoA-I (rEc-ApoA-I) was produced in Escherichia coli BL21 (DE3) expression system exhibited bacteriolyticactivity against Microcococcus lysodeikticus and Aeromonas hydrophila. Intracellular localization revealed that Ec-ApoA-I distributed in both cytoplasm and nucleus, and predominantly in the cytoplasm. Overexpression of Ec-ApoA-I in grouper Brain (GB) cells could inhibit the replication of SGIV. These results together indicated that Ec-ApoA-I perhaps is involved in the responses to bacterial and viral challenge. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Severe ocular self-injury.

    PubMed

    Field, H L; Waldfogel, S

    1995-05-01

    To further delineate the clinical characteristics of patients who deliberately, severely mutilate their eyes, we reviewed the medical records of a specialty eye hospital and found nine cases of intentional, severe, self-inflicted eye injuries. We identified two groups of patients. Most were young psychotic individuals with severe psychopathology often involving sexual and religious delusions, command hallucinations, and the propensity to act on delusions. The second group was comprised of patients with organic disabilities, either dementia or severe mental retardation, where a lack of impulse control and preexisting eye irritation or surgical operation may have contributed to the act. One patient was a recidivist. Two-thirds of the patients were confined at the time of the act. That self-mutilation may occur frequently in confined patients calls for active vigilance from caretakers; that it may recur calls for caution by the psychiatrist.

  10. Bowling for the Severely Handicapped.

    ERIC Educational Resources Information Center

    Ankenbrand, Larry J.

    Instructions are given for constructing a bowling board to aid severely physically handicapped, and wheelchair-confined individuals in bowling. A list of materials needed for building the device is included and diagrams accompany the instructions. (JD)

  11. [The cost of severe dementia].

    PubMed

    Joël, Marie-Eve

    2005-03-01

    The aim of the present article is to analyse the methodological difficulties to assess the economic cost of severe dementia from the available data, and the shortcomings of an exclusively economic approach. It is very difficult to provide a reliable account of the cost of severe dementia, when ignoring the initial assessment of the severity and the socio-economic context of the care given to demented persons. When assessing the cost of severe dementia, one needs to know who are the affected individuals, and what medical care they are given - whether at home or inside an institution. While the direct cost can be easily assessed, the indirect cost is more difficult to calculate, and particularly the productivity loss for the caring persons, when they are in occupational activity. Setting up reliable indicators for the cost of dementia is a long process, which needs a clear definition of the target population of the measurement.

  12. Comparison of shock severity measures

    SciTech Connect

    Baca, T.J.

    1989-01-01

    In an effort to clarify the issues associated with quantifying shock severity, this paper compares the merits of two measures of shock severity. The first measure is the widely used absolute acceleration shock response spectrum (SAA). The second measure of shock severity is relatively new and is known as the shock intensity spectrum (SIS). Overall information content of SAA and SIS spectra are compared and discussed in the context of two shock excitations having known amplitude, duration, and frequency content. The first is a burst of band-limited white noise and the second is a classical haversine pulse. After describing both the SAA and SIS shock measures, numerous examples are described which emphasize the strengths and limitations of each shock characterization method. This discussion reveals how the use of different shock measures may alter an engineer's conclusions about relative shock severity between two shock environments. 8 refs., 15 figs.

  13. [Severe hyponatremia revealing Sheehan's syndrome].

    PubMed

    Jousten, E; Legros, J J

    2009-01-01

    We describe the case of a young woman admitted for severe hyponatremia due to hypopituitarism caused by a Sheehan's syndrome. Sheehan's syndrome is a rare disorder. It develops after obstetrical hemorrhage that causes ischemic necrosis of the pituitary gland. In most cases, illness appears progressively and diagnosis is made after variable delay. Acute syndrome may develop immediately after delivery in some rare cases. Hyponatremia is a frequent manifestation and may be severe. It is principally caused by secondary adrenal failure.

  14. [Treatment of severe Rhesus erythroblastosis].

    PubMed

    Bichler, A; Frisch, H

    1977-01-01

    Report about the management of cases of severe Rhesus erythroblastosis. One case is specially discussed because of it's actuality. This was a patient with severe Rh-sensitization (OOD at 450 mm from the beginning of the 30th week of gestation in zone III according to Liley). Because of the haemolytic disease and the chronic fetal distress the Caesarean section was already performed in the 32nd week of gestation after Betamethason treatment of the mother. The Lecithin-Sphingomyelin (L/S) ratio in the amniotic fluid as a criterium of fetal lung maturity raised almost twicefold (from 0.9 to 1.6) after Cortison treatment. The intensive care (assisted ventilation with PEEP, correction of the acidosis and transfusion of packed red cells) of the severely anaemic (Hb 3.5 g%, Hk 15 vol.%) and hydropic newborn was already started in the delivery room. The newborn developed no RDS and was discharged healthy. With reference to this and other cases the management of severe Rh-sensitization before the 34th week of gestation is discussed. Premature infants are mainly susceptable to the development of a Respiratory Distress syndrome (RDS). After antepartum Cortison treatment for prevention of an RDS the date of confinement should be arranged earlier. The value of an early Caesarian section after antepartum Glucocorticoid treatment as compared to the application of intrauterine transfusions in cases of severe erythroblastosis is discussed. It is also reported about recent methods of treatment of severe conditions of hydrops fetalis.

  15. Apolipoprotein A-I in Labeo rohita: Cloning and functional characterisation reveal its broad spectrum antimicrobial property, and indicate significant role during ectoparasitic infection.

    PubMed

    Mohapatra, Amruta; Karan, Sweta; Kar, Banya; Garg, L C; Dixit, A; Sahoo, P K

    2016-08-01

    Apolipoprotein A-I (ApoA-I) is the most abundant and multifunctional high-density lipoprotein (HDL) having a major role in lipid transport and potent antimicrobial activity against a wide range of microbes. In this study, a complete CDS of 771 bp of Labeo rohita (rohu) ApoA-I (LrApoA-I) encoding a protein of 256 amino acids was amplified, cloned and sequenced. Tissue specific transcription analysis of LrApoA-I revealed its expression in a wide range of tissues, with a very high level of expression in liver and spleen. Ontogenic study of LrApoA-I expression showed presence of transcripts in milt and 3 h post-fertilization onwards in the larvae. The expression kinetics of LrApoA-I was studied upon infection with three different types of pathogens to elucidate its functional significance. Its expression was found to be up-regulated in the anterior kidney of L. rohita post-infection with Aeromonas hydrophila. Similarly following poly I:C (poly inosinic:cytidylic) stimulation, the transcript levels increased in both the anterior kidney and liver tissues. Significant up-regulation of LrApoA-I expression was observed in skin, mucous, liver and anterior kidney of the fish challenged with the ectoparasite Argulus siamensis. Immunomodulatory effect of recombinant LrApoA-I (rApoA-I) produced in Escherichia coli was demonstrated against A. hydrophila challenge in vivo. L. rohita administered with rApoA-I at a dose of 100 μg exhibited significantly higher protection (∼55%) upon challenge with A. hydrophila 12 h post-administration of the protein, in comparison to that observed in control group, along with higher level of expression of immune-related genes. The heightened expression of ApoA-I observed post-infection reflected its involvement in immune responses against a wide range of infections including bacterial, viral as well as parasitic pathogens. Our results also suggest the possibility of using rApoA-I as an immunostimulant, particularly rendering protection

  16. Gem and Mineral Shows as Geologic Teaching Opportunities.

    ERIC Educational Resources Information Center

    Cordua, William Sinclair

    1988-01-01

    Gem and mineral shows are excellent nontraditional opportunities for community education and outreach by geology teachers. Discusses initial club contacts, displays, shows, and the advantages of show participation to academic geologists. (CW)

  17. ApoA-I Mimetic Peptide 4F Rescues Pulmonary Hypertension by Inducing MicroRNA-193-3p

    PubMed Central

    Sharma, Salil; Umar, Soban; Potus, Francois; Iorga, Andrea; Wong, Gabriel; Meriwether, David; Breuils-Bonnet, Sandra; Mai, Denise; Navab, Kaveh; Ross, David; Navab, Mohamad; Provencher, Steeve; Fogelman, Alan M.; Bonnet, Sébastien; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2014-01-01

    Background Pulmonary Arterial Hypertension (PAH) is a chronic lung disease associated with severe pulmonary vascular changes. A pathogenic role of oxidized lipids such as hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs) is well established in vascular disease. Apolipoprotein A-I (apoA-I) mimetic peptides including 4F have been reported to reduce levels of these oxidized lipids and improve vascular disease. However, the role of oxidized lipids in the progression of PAH and the therapeutic action of 4F in PAH is not well established. Methods and Results We studied two different rodent models of Pulmonary Hypertension (PH); a monocrotaline (MCT) rat model and a hypoxia mouse model. Plasma levels of HETEs and HODEs were significantly elevated in PH. 4F treatment reduced these levels and rescued pre-existing PH in both models. MicroRNA analysis revealed that miR193-3p (miR193) was significantly downregulated in the lung tissue and in serum from both PAH patients and in PH rodents. In-vivo miR193 overexpression in the lungs rescued pre-existing PH and resulted in downregulation of lipoxygenases and insulin-like growth factor-1 receptor. 4F restored PH-induced miR193 expression via transcription factor retinoid X receptor alpha (RXRα). Conclusions These studies establish the importance of microRNAs as downstream effectors of an apoA-I mimetic peptide in the rescue of PH and suggest that treatment with apoA-I mimetic peptides, or miR193 may have therapeutic value. PMID:24963038

  18. site plan, floor plan, southeast and east elevations, detail showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    site plan, floor plan, southeast and east elevations, detail showing original front entrance, interior detail showing fireplace in elevation - Neiman House, 1930 Providence Road, Charlotte, Mecklenburg County, NC

  19. Unexpected longevity in patients with severe kyphoscoliosis.

    PubMed Central

    Rom, W N; Miller, A

    1978-01-01

    The threat of premature death in the fourth or fifth decades of life from cardiorespiratory failure in kyphoscoliosis is well known. Ten patients with severe kyphoscoliosis (curves greater than 100 degrees), who had survived into their seventh decade free of cardiorespiratory failure, were encountered over a four-year period. Pulmonary function studies on five patients showed impaired chest bellows function. Four patients died of acute respiratory failure at ages 65, 73, 79, and 85. These patients illustrate that severe deformity is not incompatible with a long and active life. PMID:644531

  20. Anemia in severe acute malnutrition.

    PubMed

    Thakur, Neha; Chandra, Jagdish; Pemde, Harish; Singh, Varinder

    2014-04-01

    India has the highest prevalence of severe acute malnutrition (SAM). Severe anemia is one of the comorbidities responsible for increased mortality in severely malnourished children, yet it has not received the attention it should. The aim of the present study was to determine the prevalence and type of anemia and to evaluate the possible etiologies for severe anemia, in these children. A cross-sectional study of patients with SAM in a tertiary care hospital in northern India over a period of 12 mo from Sept. 1, 2010 to Aug. 31, 2011 was conducted. We observed the prevalence of severe anemia (hemoglobin < 7 g/dL), morphologic type of anemia, number of patients requiring blood transfusion, hematologic profile of mothers, nature of feeding, duration of exclusive breastfeeding, and the demographic profile of these patients. Included in the study were 131 cases of SAM. The age group varied between 6 and to 59 mo. Of patients with SAM, 67.3% had severe anemia; 13.8% had moderate anemia. Of these patients, 25% required packed red blood cell transfusion. The most common type of anemia was microcytic (38.6%) followed by megaloblastic (30.5%). A high incidence of severe anemia in SAM with a large proportion (25%) requiring blood transfusion is a pointer toward nutritional anemia being a very common comorbidity of SAM requiring hospital admission. Because megaloblastic anemia closely followed microcytic anemia, supplementation with vitamin B12 in addition to iron and folic acid would be recommended. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Effect of lipid-bound apolipoprotein A-I cysteine mutant on ATF3 in RAW264.7 cells

    PubMed Central

    Wang, Yunlong; Wang, Yanhui; Jia, Shaoyou; Dong, Qingzhe; Chen, Yuanbin

    2017-01-01

    Activating transcription factor 3 (ATF3) is a TLR-induced repressor that plays an important role in the inhibition of specific inflammatory signals. We previously constructed recombinant high density lipoproteins (rHDL) (including rHDLWT, rHDLM, rHDL228 and rHDL74) and found that rHDL74 had a strong anti-inflammatory ability. In the present study, we investigate the roles of recombinant apolipoprotein A-I (ApoA-I) (rHDLWT) and its cysteine mutant HDLs (rHDLM, rHDL228 and rHDL74) on ATF3 function in RAW264.7 cells stimulated by lipopolysaccharide. Our results showed that compared with the LPS group, rHDL74 can decrease the level of TNF-α and IL-6, whereas rHDL228 increases their expression levels. RT-PCR and Western blotting results showed that compared with the LPS group, rHDL74, rHDLWT and rHDLM can markedly increase the expression level of ATF3, whereas the level of ATF3 decreases in the rHDL228 group. In summary, the different anti-inflammatory mechanisms of the ApoA-I cysteine mutants might be associated with the regulation of ATF3 level. PMID:28093456

  2. apo B gene knockout in mice results in embryonic lethality in homozygotes and neural tube defects, male infertility, and reduced HDL cholesterol ester and apo A-I transport rates in heterozygotes.

    PubMed Central

    Huang, L S; Voyiaziakis, E; Markenson, D F; Sokol, K A; Hayek, T; Breslow, J L

    1995-01-01

    apo B is a structural constituent of several classes of lipoprotein particles, including chylomicrons, VLDL, and LDL. To better understand the role of apo B in the body, we have used gene targeting in embryonic stem cells to create a null apo B allele in the mouse. Homozygous apo B deficiency led to embryonic lethality, with resorption of all embryos by gestational day 9. Heterozygotes showed an increased tendency to intrauterine death with some fetuses having incomplete neural tube closure and some live-born heterozygotes developing hydrocephalus. The majority of male heterozygotes were sterile, although the genitourinary system and sperm were grossly normal. Viable heterozygotes had normal triglycerides, but total, LDL, and HDL cholesterol levels were decreased by 37, 37, and 39%, respectively. Hepatic and intestinal apo B mRNA levels were decreased in heterozygotes, presumably contributing to the decreased LDL levels through decreased synthesis of apo B-containing lipoproteins. Kinetic studies indicated that heterozygotes had decreased transport rates of HDL cholesterol ester and apo A-I. As liver and intestinal apo A-I mRNA levels were unchanged, the mechanism for decreased apo A-I transport must be posttranscriptional. Heterozygotes also had normal cholesterol absorption and a normal response of the plasma lipoprotein pattern to chronic consumption of a high fat, high cholesterol, Western-type diet. In summary, we report a mouse model for apo B deficiency with several phenotypic features that were unexpected based on clinical studies of apo B-deficient humans, such as embryonic lethality in homozygotes and neural tube closure defects, male infertility, and a major defect in HDL production in heterozygotes. This model presents an opportunity to study the mechanisms underlying these phenotypic changes. Images PMID:7593600

  3. Severity assessment of acute pancreatitis using CT severity index and modified CT severity index: Correlation with clinical outcomes and severity grading as per the Revised Atlanta Classification.

    PubMed

    Sahu, Biswanath; Abbey, Pooja; Anand, Rama; Kumar, Ashok; Tomer, Shaili; Malik, Ekta

    2017-01-01

    To assess the severity of acute pancreatitis (AP) using computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI), to correlate with clinical outcome measures, and to assess concordance with severity grading, as per the revised Atlanta classification (RAC). In this prospective study approved by the Institutional Review Board (November 2014 to March 2016), sixty patients with AP (as per the RAC definition) underwent contrast-enhanced computed tomography (CECT) 5-11 days (median 6 days) after symptom onset. Two radiologists, blinded to clinical parameters, independently assessed CTSI and MCTSI (differences were resolved by consensus). Clinical outcome parameters included duration of stay in the hospital and intensive care unit (ICU), presence of persistent organ failure (OF), evidence of infection, need for intervention, and mortality. We included 60 cases [36 males, age range 19-65 (mean 37) years]. As per the RAC, 26 patients had mild AP, 12 moderately severe, and 22 severe AP. According to CTSI and MCTSI, mild, moderate, and severe cases were 27 (45%), 19 (31.7%), 14 (23.3%) and 24 (40%), 10 (16.7%), 26 (43.3%), respectively. MCTSI was concordant with the RAC grading in 54 (90.0%), CTSI was concordant in 47 (78.3%), and both were concordant in 43 (71.7%) cases. Area under the receiver-operating characteristic (ROC) curves (AUROC) was compared by the Hanley and McNeil method. Both CTSI and MCTSI were significantly associated with outcome parameters (P < 0.001), except duration of ICU stay. Sensitivity, specificity, positive predictive value (PPV), and accuracy of CTSI for detecting moderate/severe disease were 97.1%, 100%, 100%, and 98.3% respectively, and of MCTSI were 100%, 92.3%, 94.4%, and 96.7% respectively. Both CTSI and MCTSI showed significant correlation with clinical outcome parameters, and good concordance with RAC grading of severity. MCTSI showed a higher sensitivity but lower specificity than CTSI in differentiating mild

  4. Evaluation of several finishes on severely weathered wood

    Treesearch

    R. Sam. Williams; Peter. Sotos; William. Feist

    1999-01-01

    Alkyd-, oil-modified-latex-, and latex-based finishes were applied to severely weathered western redcedar and redwood boards that did not have any surface treatment to ameliorate the weathered surface prior to painting. Six finishes were evaluated annually for 11 years for cracking, flaking, erosion, mildew growth, discoloration, and general appearance. Low-solids-...

  5. Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters.

    PubMed

    Su, Yan Ru; Ishiguro, Hiroyuki; Major, Amy S; Dove, Dwayne E; Zhang, Wenwu; Hasty, Alyssa H; Babaev, Vladimir R; Linton, MacRae F; Fazio, Sergio

    2003-10-01

    The antiatherogenic effect of high-density lipoprotein (HDL) and its major protein component apolipoprotein A-I (apoA-I) has been largely attributed to their key roles in reverse cholesterol transport (RCT) and cellular cholesterol efflux. Substantial evidence shows that overexpression of human apoA-I reduces atherosclerosis in animal models. However, it is uncertain whether this protection is due to an increase in plasma HDL level or to a local effect in the artery wall. To test the hypothesis that expression of human apoA-I in macrophages can promote RCT in the artery wall, we used a retroviral construct expressing human apoA-I cDNA (MFG-HAI) to transduce ApoE(-/-) bone marrow cells and then transplanted these cells into ApoE(-/-) mice with preexisting atherosclerosis. ApoE(-/-) mice reconstituted with MFG-HAI marrow had a significant reduction (30%) in atherosclerotic lesions in the proximal aorta compared to control mice that received marrow expressing MFG parental virus. Peritoneal macrophages isolated from MFG-HAI mice showed a four- to fivefold increase in mRNA expression levels of both ATP-binding cassette (ABC) A1 and ABCG1 compared to controls. Our data demonstrate that gene transfer-mediated expression of human apoA-I in macrophages can compensate in part for apoE deficiency and delay the progression of atherosclerotic lesions by stimulating ABC-dependent cholesterol efflux and RCT.

  6. Severe forms of food allergy.

    PubMed

    Sarinho, Emanuel; Lins, Maria das Graças Moura

    2017-09-21

    To guide the diagnostic and therapeutic management of severe forms of food allergy. Search in the Medline database using the terms "severe food allergy," "anaphylaxis and food allergy," "generalized urticaria and food allergy," and "food protein-induced enterocolitis syndrome" in the last ten years, searching in the title, abstract, or keyword fields. Food allergy can be serious and life-threatening. Milk, eggs, peanuts, nuts, walnuts, wheat, sesame seeds, shrimp, fish, and fruit can precipitate allergic emergencies. The severity of reactions will depend on associated cofactors such as age, drug use at the onset of the reaction, history and persistence of asthma and/or severe allergic rhinitis, history of previous anaphylaxis, exercise, and associated diseases. For generalized urticaria and anaphylaxis, intramuscular epinephrine is the first and fundamental treatment line. For the treatment in acute phase of food-induced enterocolitis syndrome in the emergency setting, prompt hydroelectrolytic replacement, administration of methylprednisolone and ondansetron IV are necessary. It is important to recommend to the patient with food allergy to maintain the exclusion diet, seek specialized follow-up and, in those who have anaphylaxis, to emphasize the need to carry epinephrine. Severe food allergy may occur in the form of anaphylaxis and food-protein-induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. Gravity-dependent differentiation and root coils in Arabidopsis thaliana wild type and phospholipase-A-I knockdown mutant grown on the International Space Station.

    PubMed

    Scherer, G F E; Pietrzyk, P

    2014-01-01

    Arabidopsis roots on 45° tilted agar in 1-g grow in wave-like figures. In addition to waves, formation of root coils is observed in several mutants compromised in gravitropism and/or auxin transport. The knockdown mutant ppla-I-1 of patatin-related phospholipase-A-I is delayed in root gravitropism and forms increased numbers of root coils. Three known factors contribute to waving: circumnutation, gravisensing and negative thigmotropism. In microgravity, deprivation of wild type (WT) and mutant roots of gravisensing and thigmotropism and circumnutation (known to slow down in microgravity, and could potentially lead to fewer waves or increased coiling in both WT and mutant). To resolve this, mutant ppla-I-1 and WT were grown in the BIOLAB facility in the International Space Station. In 1-g, roots of both types only showed waving. In the first experiment in microgravity, the mutant after 9 days formed far more coils than in 1-g but the WT also formed several coils. After 24 days in microgravity, in both types the coils were numerous with slightly more in the mutant. In the second experiment, after 9 days in microgravity only the mutant formed coils and the WT grew arcuated roots. Cell file rotation (CFR) on the mutant root surface in microgravity decreased in comparison to WT, and thus was not important for coiling. Several additional developmental responses (hypocotyl elongation, lateral root formation, cotyledon expansion) were found to be gravity-influenced. We tentatively discuss these in the context of disturbances in auxin transport, which are known to decrease through lack of gravity. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  8. 42 CFR 456.655 - Validation of showings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Validation of showings. 456.655 Section 456.655... Showing of an Effective Institutional Utilization Control Program § 456.655 Validation of showings. (a) The Administrator will periodically validate showings submitted under § 456.654. Validation...

  9. 42 CFR 456.655 - Validation of showings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Validation of showings. 456.655 Section 456.655... Showing of an Effective Institutional Utilization Control Program § 456.655 Validation of showings. (a) The Administrator will periodically validate showings submitted under § 456.654. Validation...

  10. 29 CFR 34.41 - Notice to Show Cause.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Notice to Show Cause. 34.41 Section 34.41 Labor Office of... Show Cause. (a) The Director may issue a Notice to Show Cause to a recipient failing to comply with the... compliance review. (b) The Notice to Show Cause shall contain: (1) A description of the violation and a...

  11. 42 CFR 456.655 - Validation of showings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Validation of showings. 456.655 Section 456.655... Showing of an Effective Institutional Utilization Control Program § 456.655 Validation of showings. (a) The Administrator will periodically validate showings submitted under § 456.654. Validation procedures...

  12. 42 CFR 456.655 - Validation of showings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Validation of showings. 456.655 Section 456.655... Showing of an Effective Institutional Utilization Control Program § 456.655 Validation of showings. (a) The Administrator will periodically validate showings submitted under § 456.654. Validation procedures...

  13. 42 CFR 456.655 - Validation of showings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Validation of showings. 456.655 Section 456.655... Showing of an Effective Institutional Utilization Control Program § 456.655 Validation of showings. (a) The Administrator will periodically validate showings submitted under § 456.654. Validation procedures...

  14. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  15. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  16. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  17. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  18. High-Throughput Analysis Identifying Drugs That Regulate Apolipoprotein A-I Synthesis.

    PubMed

    Haas, Michael J; Onstead-Haas, Luisa; Kurban, William; Shah, Harshit; Plazarte, Monica; Chamseddin, Ayham; Mooradian, Arshag D

    2017-07-25

    Apolipoprotein A-I (apo A-I) is the primary antiatherogenic protein in high-density lipoprotein (HDL). Despite the controversy as to the clinical effectiveness of raising HDL, the search is ongoing for safe and effective drugs that increase HDL and apo A-I levels. To identify novel compounds that can increase hepatic apo A-I production, two drug libraries were screened. The NIH clinical collection (NCC) and the NIH clinical collection 2 (NCC2) were purchased from Evotec (San Francisco, CA). The NCC library contains 446 compounds and the NCC2 library contains 281 compounds, all dissolved in dimethylsulfoxide at a concentration of 10 mM. Hepatoma-derived cells (HepG2) and primary hepatocytes in culture were treated with various compounds for 24 h and apo A-I in media samples was measured by enzyme immunoassay. Samples with significant changes in apo A-I concentrations were retested in independent experiments by Western blot analysis to confirm the immunoassay findings. Of a total of 727 compounds screened at a concentration of 50 μM, 15 compounds increased hepatic apo A-I production by 35%-54%, and 9 compounds lowered hepatic apo A-I concentrations in the culture media by 25%-52%. Future trials should explore the clinical effectiveness of these agents when standard doses of these drugs are used in humans.

  19. Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma.

    PubMed

    Luo, Xiao-Lin; Zhong, Guang-Zheng; Hu, Li-Yang; Chen, Jie; Liang, Ying; Chen, Qiu-Yan; Liu, Qing; Rao, Hui-Lan; Chen, Kai-Lin; Cai, Qing-Qing

    2015-12-22

    We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC). We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I. The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis. Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.

  20. 22 CFR 214.3 - A.I.D. Advisory Committee Management Officer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false A.I.D. Advisory Committee Management Officer. 214.3 Section 214.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADVISORY COMMITTEE MANAGEMENT General § 214.3 A.I.D. Advisory Committee Management Officer. The Advisory Committee Management...

  1. Matrix metalloproteinase 8 degrades apolipoprotein A-I and reduces its cholesterol efflux capacity.

    PubMed

    Salminen, Aino; Åström, Pirjo; Metso, Jari; Soliymani, Rabah; Salo, Tuula; Jauhiainen, Matti; Pussinen, Pirkko J; Sorsa, Timo

    2015-04-01

    Various cell types in atherosclerotic lesions express matrix metalloproteinase (MMP)-8. We investigated whether MMP-8 affects the structure and antiatherogenic function of apolipoprotein (apo) A-I, the main protein component of HDL particles. Furthermore, we studied serum lipid profiles and cholesterol efflux capacity in MMP-8-deficient mouse model. Incubation of apoA-I (28 kDa) with activated MMP-8 yielded 22 kDa and 25 kDa apoA-I fragments. Mass spectrometric analyses revealed that apoA-I was cleaved at its carboxyl-terminal part. Treatment of apoA-I and HDL with MMP-8 resulted in significant reduction (up to 84%, P < 0.001) in their ability to facilitate cholesterol efflux from cholesterol-loaded THP-1 macrophages. The cleavage of apoA-I by MMP-8 and the reduction in its cholesterol efflux capacity was inhibited by doxycycline. MMP-8-deficient mice had significantly lower serum triglyceride (TG) levels (P = 0.003) and larger HDL particles compared with wild-type (WT) mice. However, no differences were observed in the apoA-I levels or serum cholesterol efflux capacities between the mouse groups. Proteolytic modification of apoA-I by MMP-8 may impair the first steps of reverse cholesterol transport, leading to increased accumulation of cholesterol in the vessel walls. Eventually, inhibition of MMPs by doxycycline may reduce the risk for atherosclerotic vascular diseases.

  2. Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

    USDA-ARS?s Scientific Manuscript database

    Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon 22, Q[22]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in...

  3. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  4. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  5. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  6. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  7. 22 CFR 204.33 - A.I.D. approval of acceleration of notes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false A.I.D. approval of acceleration of notes. 204.33 Section 204.33 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Covenants § 204.33 A.I.D. approval of acceleration of notes. Without the...

  8. Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I Metabolism: A Systematic Overview

    PubMed Central

    Smolders, Lotte; Plat, Jogchum

    2017-01-01

    The incidence of CHD is still increasing, which underscores the need for new preventive and therapeutic approaches to decrease CHD risk. In this respect, increasing apoA-I concentrations may be a promising approach, especially through increasing apoA-I synthesis. This review first provides insight into current knowledge on apoA-I production, clearance, and degradation, followed by a systematic review of dietary and novel pharmacological approaches to target apoA-I metabolism. For this, a systematic search was performed to identify randomized controlled intervention studies that examined effects of whole foods and (non)nutrients on apoA-I metabolism. In addition, novel pharmacological approaches were searched for, which were specifically developed to target apoA-I metabolism. We conclude that both dietary components and pharmacological approaches can be used to increase apoA-I concentrations or functionality. For the dietary components in particular, more knowledge about the underlying mechanisms is necessary, as increasing apoA-I per se does not necessarily translate into a reduced CHD risk. PMID:28695008

  9. Severe cutaneous adverse drug reactions

    PubMed Central

    Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran

    2013-01-01

    Severe cutaneous drug reactions are one of the commonest medical challenges presenting to an emergency room in any hospital. The manifestations range from maculopapular rash to severe systemic symptoms like renal failure and cardiovascular compromise. Toxic epidermal necrolysis, erythroderma, drug rash with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis and drug induced vasculitis are the common cutaneous drug reactions which can have severe morbidity and even mortality. Careful history taking of the lag period after drug intake and associated symptoms, along with detailed examination of the skin, mucosa and various systems, help in early diagnosis of these reactions. Early stoppage of the incriminating drug, specific therapy including corticosteroids, cyclosporine and intravenous immunoglobulin depending on the case along with supportive therapy and local measures help in salvaging most patients. An overview of these important cutaneous drug reactions along with their management is being reviewed in this article. PMID:24600147

  10. Finite frequency tomography shows a variety of plumes

    NASA Astrophysics Data System (ADS)

    Nolet, G.; Montelli, R.; Masters, G.; Dahlen, F. A.; Hung, S.

    2003-04-01

    The new technique of finite-frequency tomography (see abstract by Montelli et al., this meeting) is very powerful in imaging objects of small dimension in the lower mantle. The first global images of P velocity anomalies obtained by using this technique to invert a small but very accurate data set of long period P arrivals bottoming in the lower mantle show 18 low velocity anomalies in excess of -0.5%, all but two of which are associated with a known hotspot at the surface, and they serve as an unprecented glimpse into the deep mechanisms that give rise to hotspots. The following synopsis is given under the caveat that we have not yet incorporated high frequency waves into the interpretation, nor completed a full resolution analysis at the time of writing of this abstract (both will be presented at the meeting). We observe six or seven hotspots fed by a plume extending to the core-mantle boundary: Cap Verde, Easter Island, Hawaii, Kerguelen, St Helena, Tahiti, and perhaps also Azores. Several hotspots, among which are Bouvet, Bowie, and Mount Erebus, seem to originate at mid-mantle depth, while others (Afar, Ascension, Galapagos, Iceland, la Reunion and others) seem to be mostly confined to the upper mantle. Many renowned hotspots (such as Eifel, Samoa and Yellowstone) have only very weak low velocity anomalies at depth and may be the result of superficial processes confined to the top of the upper mantle. We confirm the existence of the two superplumes which both have Δ V_P < -0.5% extending as high as 2000 km depth. It is clear that no one plume/hotspot model can explain the variety in deep expressions of hotspots in the mantle. If midmantle plume origins represent originally deep plumes in their end stage, while the two unidentified anomalies are either beginning new plumes (Greenland) or plumes cut off in their initial ascent (W. Pacific), the large number of plumes caught in this phase would point to lengthy rise times of the order of tens of millions of

  11. Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO mice: comparison of intramuscular and intravenous administration.

    PubMed

    Cimmino, Giovanni; Giannarelli, Chiara; Chen, Wei; Alique, Matilde; Santos-Gallego, Carlos G; Fuster, Valentin; Hajjar, Roger J; Walsh, Christopher E; Badimon, Juan J

    2011-03-01

    Apolipoprotein A-I (ApoA-I)/high-density lipoprotein (HDL)-raising treatments are effective antiatherosclerotic strategies. We have compared the antiatherogenic effects of human ApoA-I (hApoA-I) overexpression by intraportal and intramuscular gene transfer in atherosclerotic ApoE-knockout mice. Atherosclerotic lesions were induced by atherogenic diet. After atherosclerosis induction, a group of animals was killed and served as atherosclerosis baseline-control group. The remaining animals were randomized into the following groups: (1) atherosclerosis-progression-control, (2) intraportal/vector administration, and (3) intramuscular/vector administration. Aortas and hearts were processed for atherosclerotic quantification by en face Sudan IV and Oil Red-O, respectively. Liver and muscle specimens were processed for protein/gene expression analysis. A sustained increase in hApoA-I/HDL plasma levels was observed in both transduced groups. hApoA-I overexpression abolished plaque progression versus progression-control group. hApoA-I overexpression significantly reduced lesion macrophage, feature indicative of plaque stabilization. Scavenger receptor class-B type I (SR-BI), but not ATP-binding cassette, sub-family A (ABCA), member 1 (ABCA-1), was significantly upregulated in treated groups versus progression-controls. The results of this study show a similar effect of hApoA-I/HDL overexpression on plaque progression/stabilization by 2 different routes of administration. Our results showing similar effects using either intramuscular administration and intraportal route of administration may have significant clinical implications, given the reduced medical risk to patient and cost of intramuscular injections.

  12. [Severe sepsis and septic shock].

    PubMed

    Tønnesen, Else; Larsen, Kim

    2014-07-07

    Sepsis, severe sepsis and septic shock are syndromes. The incidence of sepsis is as high as 35% and with mortality rates in the intensive care unit from 27% to 54% in sepsis and septic shock, respectively. Many new treatments have been tested but only few have been implemented in clinical practise. The treatment of severe sepsis and septic shock is based on the Surviving Sepsis Campaign guidelines developed by an international expert panel. Early diagnosis, optimization of haemodynamics, rapid identification of focus and adequate antibiotic treatment are the most important strategies.

  13. Treatment of severe orthopedic infections.

    PubMed

    Dernell, W S

    1999-09-01

    Severe infections are uncommon following orthopedic surgery, yet they can be frustrating for the veterinarian and owner to treat and can result in devastating consequences for the patient. This article reviews the common causes for postoperative infection, reviews established treatment, and introduces newer methods for treatment and control. A thorough understanding of the pathogenesis, application of appropriate diagnostic procedures, the institution of aggressive treatment regimens, with adherence to established principles, will often result in satisfactory outcomes even with severe orthopedic infections. For those more refractory to treatment, the use of newer treatment methods, specifically locally implantable materials for sustained release of antimicrobials can improve success in the treatment of these more difficult cases.

  14. Fluid Resuscitation in Severe Sepsis.

    PubMed

    Loflin, Rob; Winters, Michael E

    2017-02-01

    Since its original description in 1832, fluid resuscitation has become the cornerstone of early and aggressive treatment of severe sepsis and septic shock. However, questions remain about optimal fluid composition, dose, and rate of administration for critically ill patients. This article reviews pertinent physiology of the circulatory system, pathogenesis of septic shock, and phases of sepsis resuscitation, and then focuses on the type, rate, and amount of fluid administration for severe sepsis and septic shock, so providers can choose the right fluid, for the right patient, at the right time.

  15. Quality of survival after severe birth asphyxia.

    PubMed Central

    Thomson, A J; Searle, M; Russell, G

    1977-01-01

    Thirty-one children who survived severe birth asphyxia defined by a 1-minute Apgar score of 0, or a 5-minute Apgar score of less than 4, have been seen at age 5 to 10 years for neurological and psychological assessment. Their progress has been compared with that of controls matched for sex, birthweight, gestational age, and social class. 29(93%) of the 31 asphyxiated group and all the controls had no serious neurological or mental handicap. 2 were severely disabled and mentally retarded. Detailed studies of psychological function showed no significant differences between the two groups. 2 apparently stillborn infants have made normal progress. It was not possible to identify any perinatal factor which predicted the occurrence of serious handicap with certainty. We considered that the quality of life enjoyed by the large majority of the survivors was such as to justify a positive approach to the resuscitation of very severely asphyxiated neonates. PMID:921307

  16. Algebra in a man with severe aphasia.

    PubMed

    Klessinger, Nicolai; Szczerbinski, Marcin; Varley, Rosemary

    2007-04-09

    We report a dissociation between higher order mathematical ability and language in the case of a man (SO) with severe aphasia. Despite severely impaired abilities in the language domain and difficulties with processing both phonological and orthographic number words, he was able to judge the equivalence of and to transform and simplify mathematical expressions in algebraic notation. SO was sensitive to structure-dependent properties of algebraic expressions and displayed considerable capacity to retrieve algebraic facts, rules and principles, and to apply them to novel problems. He demonstrated similar capacity in solving expressions containing either solely numeric or abstract algebraic symbols (e.g., 8-(3-5)+3 versus b-(a-c)+a). The results show the retention of elementary algebra despite severe aphasia and provide evidence for the preservation of symbolic capacity in one modality and hence against the notion of aphasia as asymbolia.

  17. X-31 Unloading Returning from Paris Air Show

    NASA Technical Reports Server (NTRS)

    1995-01-01

    After being flown in the Paris Air Show in June 1995, the X-31 Enhanced Fighter Maneuverability Technology Demonstrator Aircraft, based at the NASA Dryden Flight Research Center, Edwards Air Force Base, California, is off-loaded from an Air Force Reserve C-5 transport after the ferry flight back to Edwards. At the air show, the X-31 demonstrated the value of using thrust vectoring (directing engine exhaust flow) coupled with advanced flight control systems to provide controlled flight at very high angles of attack. The X-31 Enhanced Fighter Maneuverability (EFM) demonstrator flew at the Ames- Dryden Flight Research Facility, Edwards, California (redesignated the Dryden Flight Research Center in 1994) from February 1992 until 1995 and before that at the Air Force's Plant 42 in Palmdale, California. The goal of the project was to provide design information for the next generation of highly maneuverable fighter aircraft. This program demonstrated the value of using thrust vectoring (directing engine exhaust flow) coupled with an advanced flight control system to provide controlled flight to very high angles of attack. The result was a significant advantage over most conventional fighters in close-in combat situations. The X-31 flight program focused on agile flight within the post-stall regime, producing technical data to give aircraft designers a better understanding of aerodynamics, effectiveness of flight controls and thrust vectoring, and airflow phenomena at high angles of attack. Stall is a condition of an airplane or an airfoil in which lift decreases and drag increases due to the separation of airflow. Thrust vectoring compensates for the loss of control through normal aerodynamic surfaces that occurs during a stall. Post-stall refers to flying beyond the normal stall angle of attack, which in the X-31 was at a 30-degree angle of attack. During Dryden flight testing, the X-31 aircraft established several milestones. On November 6, 1992, the X-31 achieved

  18. Overexpression of apolipoprotein A-I alleviates endoplasmic reticulum stress in hepatocytes.

    PubMed

    Guo, Qing; Zhang, Can; Wang, Yutong

    2017-06-02

    Abnormal lipid metabolism may contribute to an increase in endoplasmic reticulum (ER) stress, resulting in the pathogenesis of non-alcoholic steatohepatitis. Apolipoprotein A-I (apoA-I) accepts cellular free cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies have revealed that the overexpression of apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effects of apoA-I overexpression on ER stress and genes involved in lipogenesis in both HepG2 cells and mouse hepatocytes. Human apoA-I was overexpressed in HepG2 hepatocytes, which were then treated with 2 μg/mL tunicamycin or 500 μM palmitic acid. Eight-week-old male apoA-I transgenic or C57BL/6 wild-type mice were intraperitoneally injected with 1 mg/kg body weight tunicamycin or with saline. At 48 h after injecting, blood and liver samples were collected. The overexpression of apoA-I in the models above resulted in decreased protein levels of ER stress makers and lipogenic gene products, including sterol regulatory element binding protein 1, fatty acid synthase, and acetyl-CoA carboxylase 1. In addition, the cellular levels of triglycerides and free cholesterol also decreased. Some of gene products which are related to ER stress-associated apoptosis were also affected by apoA-I overexpression. These results suggested that apoA-I overexpression could reduce steatosis by decreasing lipid levels and by suppressing ER stress and lipogenesis in hepatocytes. ApoA-I expression could significantly reduce hepatic ER stress and lipogenesis in hepatocytes.

  19. Restoration of severely weathered wood

    Treesearch

    R. Sam. Williams; Mark. Knaebe

    2000-01-01

    Severely weathered window units were used to test various restoration methods and pretreatments. Sanded and unsanded units were pretreated with a consolidant or water repellent preservative, finished with an oil- or latex-based paint system, and exposed outdoors near Madison, WI, for five years. Pretreatments were applied to both window sashes (stiles and rails) and...

  20. Polyradiculopathy secondary to severe hypertriglyceridemia.

    PubMed

    Nesbitt, Cassie; Wong, Daniel; Batchelor, Peter

    2015-05-08

    A 74-year-old man presented with a subacute severe thoracic polyradiculopathy affecting the T4-T8 dermatomes bilaterally. Extensive investigation demonstrated markedly raised triglyceride levels of 44 mmol/L (<1.7). The patient's unique presentation is discussed alongside a review of triglyceride-induced neurotoxicity and therapeutic management.

  1. Severe Weather Forecast Decision Aid

    NASA Technical Reports Server (NTRS)

    Bauman, William H., III; Wheeler, Mark

    2005-01-01

    The Applied Meteorology Unit developed a forecast tool that provides an assessment of the likelihood of local convective severe weather for the day in order to enhance protection of personnel and material assets of the 45th Space Wing Cape Canaveral Air Force Station (CCAFS), and Kennedy Space Center (KSC).

  2. Coagulopathy after severe pediatric trauma.

    PubMed

    Christiaans, Sarah C; Duhachek-Stapelman, Amy L; Russell, Robert T; Lisco, Steven J; Kerby, Jeffrey D; Pittet, Jean-François

    2014-06-01

    Trauma remains the leading cause of morbidity and mortality in the United States among children aged 1 to 21 years. The most common cause of lethality in pediatric trauma is traumatic brain injury. Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. In contrast to adult patients, massive bleeding is less common after pediatric trauma. The classical drivers of trauma-induced coagulopathy include hypothermia, acidosis, hemodilution, and consumption of coagulation factors secondary to local activation of the coagulation system after severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of trauma-induced coagulopathy that involves the activation of the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of coagulopathy. Finally, we discuss different options for treating coagulopathy after severe pediatric trauma.

  3. Stuttering Severity and Educational Attainment

    ERIC Educational Resources Information Center

    O'Brian, Sue; Jones, Mark; Packman, Ann; Menzies, Ross; Onslow, Mark

    2011-01-01

    Purpose: This study investigated the relationship between self-reported stuttering severity ratings and educational attainment. Method: Participants were 147 adults seeking treatment for stuttering. At pretreatment assessment, each participant reported the highest educational level they had attained and rated their typical and worst stuttering…

  4. Severe thunderstorms and climate change

    NASA Astrophysics Data System (ADS)

    Brooks, H. E.

    2013-04-01

    As the planet warms, it is important to consider possible impacts of climate change on severe thunderstorms and tornadoes. To further that discussion, the current distribution of severe thunderstorms as a function of large-scale environmental conditions is presented. Severe thunderstorms are much more likely to form in environments with large values of convective available potential energy (CAPE) and deep-tropospheric wind shear. Tornadoes and large hail are preferred in high-shear environments and non-tornadic wind events in low shear. Further, the intensity of tornadoes and hail, given that they occur, tends to be almost entirely a function of the shear and only weakly depends on the thermodynamics. Climate model simulations suggest that CAPE will increase in the future and the wind shear will decrease. Detailed analysis has suggested that the CAPE change will lead to more frequent environments favorable for severe thunderstorms, but the strong dependence on shear for tornadoes, particularly the strongest ones, and hail means that the interpretation of how individual hazards will change is open to question. The recent development of techniques to use higher-resolution models to estimate the occurrence of storms of various kinds is discussed. Given the large interannual variability in environments and occurrence of events, caution is urged in interpreting the observational record as evidence of climate change.

  5. Severe convective environments in Reanalyses

    NASA Astrophysics Data System (ADS)

    Gutierrez, G.; Kennedy, A. D.

    2014-12-01

    Climate change implies an altering of weather patterns that may change the frequency of high impact events such as severe thunderstorms and their associated dangers (damaging winds, torrential rains, hail, and tornadoes). Presently, very little is known about how climate change will impact these events. Since these phenomenon are not resolved by climate models, proxies are required to understand how these events may change in the future.Prior to investigating how convective environments change in the future, a reference must be obtained to understand the current climatology of convective environments. Studies such as Kennedy et al. (2011) have shown there are significant differences in reanalyses for regions prone to severe weather.Severe weather parameters such as Convective Available Potential Energy (CAPE), Lifted Index, K Index, Total Totals, 0-1 km shear, 0-3 km shear and 0-6 km shear are calculated using soundings from reanalyses for known severe convective environments. Reanalyses included in this study are the North American Regional Reanalysis (NARR), Modern-Era Retrospective Analysis for Research and Applications (MERRA), 20th Century Reanalysis (20CR), Climate Forecast System Reanalysis (CFSR), Japanese 25-year Reanalysis (JRA25), and Japanese 55-year Reanalysis (JRA55). Preliminary findings are presented. If time allows, multi-parameter indices such as Energy Helicity Index, Bunkers storm motion, Significant Tornado Parameter, and Supercell Composite Parameter will also be compared.

  6. Water Recreation and Illness Severity

    EPA Science Inventory

    Abstract Background: The health endpoint of prior studies of water recreation has been the occurrence gastrointestinal (GI) of illness. The use of this dichotomous health outcome fails to take into account the range of symptom severity among those with GI illness, as well as thos...

  7. Severe allergic reaction to Dermabond.

    PubMed

    Perry, Arthur W; Sosin, Michael

    2009-01-01

    The use of 2-octyl cyanoacrylate (Dermabond; Ethicon, Somerville, NJ) for wound closure is increasingly popular. Problems with Dermabond are generally related to application techniques and rarely relate to the chemical nature of the adhesive. This article describes a severe allergic reaction to Dermabond following breast augmentation/mastopexy.

  8. Stuttering Severity and Educational Attainment

    ERIC Educational Resources Information Center

    O'Brian, Sue; Jones, Mark; Packman, Ann; Menzies, Ross; Onslow, Mark

    2011-01-01

    Purpose: This study investigated the relationship between self-reported stuttering severity ratings and educational attainment. Method: Participants were 147 adults seeking treatment for stuttering. At pretreatment assessment, each participant reported the highest educational level they had attained and rated their typical and worst stuttering…

  9. Water Recreation and Illness Severity

    EPA Science Inventory

    Abstract Background: The health endpoint of prior studies of water recreation has been the occurrence gastrointestinal (GI) of illness. The use of this dichotomous health outcome fails to take into account the range of symptom severity among those with GI illness, as well as thos...

  10. Severe Malnutrition: A Global Approach.

    ERIC Educational Resources Information Center

    Pelletier, Jean-Gerard

    1993-01-01

    This report examines the immediate and underlying causes of malnutrition in the developing world. The first section discusses the effects of malnutrition on childhood development and examines the efficacy of nutritional rehabilitation. The second section addresses the medical effects of severe malnutrition, including the onset of ponderostatural…

  11. [Management of severe arterial hypertension].

    PubMed

    Leeman, M

    2015-09-01

    Severe arterial hypertension is defined as a systolic blood pressure (BP) ≥180 mmHg and/or a diastolic BP ≥ 110 mmHg. Initial assessment is to identify acute, ongoing, target-organ damage such as pulmonary edema, aortic dissection, ... (hypertensive emergency). If so, the patient requires urgent and specific management in a hospital setting. More commonly, however, BP in the severe range is relatively asymptomatic and not associated with end-organ damage (hypertensive urgency). Management can usually be carried out in the ambulatory setting. Severe hypertension should first be confirmed after a period of rest in a quiet room. If BP remains in the severe range, an antihypertensive drug can be initiated. Otherwise, the patient should be referred for further evaluation within a few days ; however, an antihypertensive treatment could be started immediately if there is concern that urgent outpatient follow-up cannot be ensured or if the patient is at high cardiovascular risk. The choice of the first drug should be tailored according to associated conditions and possible contraindications. Some guidelines recommend starting therapy with an antihypertensive combination of two drugs. In all cases, rapid and excessive reduction in BP, which could compromise organ perfusion, must be avoided, especially in elderly patients. In the short-term (days), BP should be progressively lowered to < 160/100 mmHg. In the long term, a BP < 140/90 mmHg should be obtained.

  12. Positive lightning and severe weather

    NASA Astrophysics Data System (ADS)

    Price, C.; Murphy, B.

    2003-04-01

    In recent years researchers have noticed that severe weather (tornados, hail and damaging winds) are closely related to the amount of positive lightning occurring in thunderstorms. On 4 July 1999, a severe derecho (wind storm) caused extensive damage to forested regions along the United States/Canada border, west of Lake Superior. There were 665,000 acres of forest destroyed in the Boundary Waters Canoe Area Wilderness (BWCAW) in Minnesota and Quetico Provincial Park in Canada, with approximately 12.5 million trees blown down. This storm resulted in additional severe weather before and after the occurrence of the derecho, with continuous cloud-to-ground (CG) lightning occurring for more than 34 hours during its path across North America. At the time of the derecho the percentage of positive cloud-to-ground (+CG) lightning measured by the Canadian Lightning Detection Network (CLDN) was greater than 70% for more than three hours, with peak values reaching 97% positive CG lightning. Such high ratios of +CG are rare, and may be useful indicators for short-term forecasts of severe weather.

  13. Directory, Projects for Severely Handicapped.

    ERIC Educational Resources Information Center

    Yeshiva Univ., New York, NY. Curriculum Research and Development Center in Mental Retardation.

    Presented is a directory of 169 projects for severely handicapped persons. Descriptions include title of project, director's name, project address and telephone number, target population, designation of personnel (including teacher, medical personnel, and psychologist) involved in training, project areas (such as staff training, communication and…

  14. Are Educational Shows Teaching Our Children to Become Life-Long Learners?

    ERIC Educational Resources Information Center

    Sullins, Jeremiah; Howard, Tiffany; Goza, Kimberly

    2014-01-01

    The purpose of this study was to investigate various textual characteristics of popular children television shows. More specifically, researchers examined both the quantity and quality of question asked (i.e., question training). Furthermore, several readability components among the different shows (e.g., narrativity, syntactic simplicity,…

  15. Are Educational Shows Teaching Our Children to Become Life-Long Learners?

    ERIC Educational Resources Information Center

    Sullins, Jeremiah; Howard, Tiffany; Goza, Kimberly

    2014-01-01

    The purpose of this study was to investigate various textual characteristics of popular children television shows. More specifically, researchers examined both the quantity and quality of question asked (i.e., question training). Furthermore, several readability components among the different shows (e.g., narrativity, syntactic simplicity,…

  16. Serotonin and interleukin-6: Association with pruritus severity, sleep quality and depression severity in Prurigo Nodularis.

    PubMed

    Konda, Deepthi; Chandrashekar, Laxmisha; Rajappa, Medha; Kattimani, Shivanand; Thappa, Devinder Mohan; Ananthanarayanan, P H

    2015-10-01

    Prurigo Nodularis (PN) is a chronic skin condition of unknown etiology. It is said to be associated with psychological factors. However, studies to identify the same are few. Hence, we undertook to assess the association between quality of sleep, depression, pruritus severity in cases of PN and to assess association of serum serotonin, interleukin (IL)-6 with sleep, depression and pruritus severity. This cross-sectional study involves 39 patients with PN and 39 age and gender matched healthy controls. Subjective quality of sleep, depressive symptom severity and pruritus severity were collected through clinician based interview. Serum serotonin and serum IL-6 were estimated by ELISA. Spearman correlation was used to assess the strength of association between biochemical parameters and clinical parameters. Cases had significantly higher percentage of depression, a higher score of depression severity, higher serum IL-6 level and lower serum serotonin levels. Serum serotonin and serum IL-6 showed significant correlation with the severity of pruritus (r=-0.66, p<0.01 and r=0.60, p<0.01). However, both these parameters showed a significantly negative correlation between them (r=-0.92, p<0.01). Though cause and effect cannot be established in this type of study, there is a disturbance of the inflammatory-neuroendocrine axis (interleukins-serotonin). PN is characterized by higher IL-6 and lower serotonin and greater depression severity than healthy controls. Findings of this study may have an influence on the treatment of PN.

  17. Associations of apolipoprotein B/apolipoprotein A-I ratio with pre-diabetes and diabetes risks: a cross-sectional study in Chinese adults.

    PubMed

    Zheng, Shuang; Han, Tingting; Xu, Hua; Zhou, Huan; Ren, Xingxing; Wu, Peihong; Zheng, Jun; Wang, Lihua; Zhang, Ming; Jiang, Yihong; Chen, Yawen; Qiu, Huiying; Liu, Wei; Hu, Yaomin

    2017-01-20

    Apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio is a useful predictor of cardiovascular risk. However, the association between the ApoB/ApoA-I ratio and the risk of type 2 diabetes mellitus (T2DM) is still obscure. To investigate the associations between the ApoB/ApoA-I ratio and the risk of T2DM and pre-diabetes in a Chinese population, and to assess the role of gender in these associations. A stratified random sampling design was used in this cross-sectional study which included 264 men and 465 women with normal glucose tolerance (NGT), pre-diabetes or T2DM. Serum ApoB, ApoA-I and other lipid and glycaemic traits were measured. Pearson's partial correlation and multivariable logistic analysis were used to evaluate the associations between ApoB/ApoA-I ratio and the risk of T2DM and pre-diabetes. The ApoB/ApoA-I ratios were significantly increased across the spectrum of NGT, pre-diabetes and T2DM. Women showed higher levels of ApoB/ApoA-I ratio and ApoB than men in the pre-diabetic and T2DM groups, but not in the NGT group. The ApoB/ApoA-I ratio was closely related with triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other glycaemic traits. Moreover, in women, the risk of diabetes and pre-diabetes in the top and middle tertiles of the ApoB/ApoA-I ratio were 3.65-fold (95% CI 1.69 to 6.10) and 2.19-fold (95% CI 1.38 to 2.84) higher than in the bottom tertile, respectively, after adjusting for potential confounding factors. However, the associations disappeared in men after adjusting for other factors. The ApoB/ApoA-I ratio showed positive associations with the risk of diabetes and pre-diabetes in Chinese women. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Associations of apolipoprotein B/apolipoprotein A-I ratio with pre-diabetes and diabetes risks: a cross-sectional study in Chinese adults

    PubMed Central

    Zheng, Shuang; Han, Tingting; Xu, Hua; Zhou, Huan; Ren, Xingxing; Wu, Peihong; Zheng, Jun; Wang, Lihua; Zhang, Ming; Jiang, Yihong; Chen, Yawen; Qiu, Huiying; Liu, Wei; Hu, Yaomin

    2017-01-01

    Background Apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio is a useful predictor of cardiovascular risk. However, the association between the ApoB/ApoA-I ratio and the risk of type 2 diabetes mellitus (T2DM) is still obscure. Aims To investigate the associations between the ApoB/ApoA-I ratio and the risk of T2DM and pre-diabetes in a Chinese population, and to assess the role of gender in these associations. Methods A stratified random sampling design was used in this cross-sectional study which included 264 men and 465 women with normal glucose tolerance (NGT), pre-diabetes or T2DM. Serum ApoB, ApoA-I and other lipid and glycaemic traits were measured. Pearson's partial correlation and multivariable logistic analysis were used to evaluate the associations between ApoB/ApoA-I ratio and the risk of T2DM and pre-diabetes. Results The ApoB/ApoA-I ratios were significantly increased across the spectrum of NGT, pre-diabetes and T2DM. Women showed higher levels of ApoB/ApoA-I ratio and ApoB than men in the pre-diabetic and T2DM groups, but not in the NGT group. The ApoB/ApoA-I ratio was closely related with triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other glycaemic traits. Moreover, in women, the risk of diabetes and pre-diabetes in the top and middle tertiles of the ApoB/ApoA-I ratio were 3.65-fold (95% CI 1.69 to 6.10) and 2.19-fold (95% CI 1.38 to 2.84) higher than in the bottom tertile, respectively, after adjusting for potential confounding factors. However, the associations disappeared in men after adjusting for other factors. Conclusions The ApoB/ApoA-I ratio showed positive associations with the risk of diabetes and pre-diabetes in Chinese women. PMID:28110289

  19. Using Image Processing to Determine Emphysema Severity

    NASA Astrophysics Data System (ADS)

    McKenzie, Alexander; Sadun, Alberto

    2010-10-01

    Currently X-rays and computerized tomography (CT) scans are used to detect emphysema, but other tests are required to accurately quantify the amount of lung that has been affected by the disease. These images clearly show if a patient has emphysema, but are unable by visual scan alone, to quantify the degree of the disease, as it presents as subtle, dark spots on the lung. Our goal is to use these CT scans to accurately diagnose and determine emphysema severity levels in patients. This will be accomplished by performing several different analyses of CT scan images of several patients representing a wide range of severity of the disease. In addition to analyzing the original CT data, this process will convert the data to one and two bit images and will then examine the deviation from a normal distribution curve to determine skewness. Our preliminary results show that this method of assessment appears to be more accurate and robust than the currently utilized methods, which involve looking at percentages of radiodensities in the air passages of the lung.

  20. Prevalence, predictors and economic consequences of no-shows.

    PubMed

    Kheirkhah, Parviz; Feng, Qianmei; Travis, Lauren M; Tavakoli-Tabasi, Shahriar; Sharafkhaneh, Amir

    2016-01-14

    Patients not attending to clinic appointments (no-show) significantly affects delivery, cost of care and resource planning. We aimed to evaluate the prevalence, predictors and economic consequences of patient no-shows. This is a retrospective cohort study using administrative databases for fiscal years 1997-2008. We searched administrative databases for no-show frequency and cost at a large medical center. In addition, we estimated no-show rates and costs in another 10 regional hospitals. We studied no-show rates in primary care and various subspecialty settings over a 12-year period, the monthly and seasonal trends of no-shows, the effects of implementing a reminder system and the economic effects of missed appointments. The mean no-show rate was 18.8% (2.4%) in 10 main clinics with highest occurring in subspecialist clinics. No-show rate in the women clinic was higher and the no-show rate in geriatric clinic was lower compared to general primary care clinic (PCP). The no-show rate remained at a high level despite its reduction by a centralized phone reminder (from 16.3% down to 15.8%). The average cost of no-show per patient was $196 in 2008. Our data indicates that no-show imposed a major burden on this health care system. Further, implementation of a reminder system only modestly reduced the no-show rate.