41 CFR 102-74.180 - What illumination levels must Federal agencies maintain on Federal facilities?

Code of Federal Regulations, 2010 CFR

2010-07-01

... surfaces, measured at a height of 30 inches above floor level, during working hours (for visually difficult...) 30 foot-candles in work areas during working hours, measured at 30 inches above floor level; (c) 10 foot-candles, but not less than 1 foot-candle, in non-work areas, during working hours (normally this...

Regulatory effect of acetyl-l-carnitine on expression of lenticular antioxidant and apoptotic genes in selenite-induced cataract.

PubMed

Elanchezhian, R; Sakthivel, M; Geraldine, P; Thomas, P A

2010-03-30

Differential expression of apoptotic genes has been demonstrated in selenite-induced cataract. Acetyl-l-carnitine (ALCAR) has been shown to prevent selenite cataractogenesis by maintaining lenticular antioxidant enzyme and redox system components at near normal levels and also by inhibiting lenticular calpain activity. The aim of the present experiment was to investigate the possibility that ALCAR also prevents selenite-induced cataractogenesis by regulating the expression of antioxidant (catalase) and apoptotic [caspase-3, early growth response protein-1 (EGR-1) and cytochrome c oxidase subunit I (COX-I)] genes. The experiment was conducted on 9-day-old Wistar rat pups, which were divided into normal, cataract-untreated and cataract-treated groups. Putative changes in gene expression in whole lenses removed from the rats were determined by measuring mRNA transcript levels of the four genes by RT-PCR analysis, using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal control. The expression of lenticular caspase-3 and EGR-1 genes appeared to be upregulated, as inferred by detecting increased mRNA transcript levels, while that of COX-I and catalase genes appeared to be downregulated (lowered mRNA transcript levels) in the lenses of cataract-untreated rats. However, in rats treated with ALCAR, the lenticular mRNA transcript levels were maintained at near normal (control) levels. These results suggest that ALCAR may prevent selenite-induced cataractogenesis by preventing abnormal expression of lenticular genes governing apoptosis.

Blood Volume Response to Physical Activity and Inactivity

DTIC Science & Technology

2007-07-01

feedback to promote volume excretion and maintain blood volume at its normal baseline level. Physical activity does not alter either arterial pressure or...although this is less clear. The increase in total blood volume then increases the ability to maintain a high stroke volume and a lower heart rate for...compelling evidence that reduced blood vol- ume with age may be a result of a sedentary, high caloric lifestyle rather than the aging process. There

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

PubMed

Wolf, Myles; White, Kenneth E

2014-07-01

High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Reactive Oxygen Species in Normal and Tumor Stem Cells

PubMed Central

Zhou, Daohong; Shao, Lijian; Spitz, Douglas R.

2014-01-01

Reactive oxygen species (ROS) play an important role in determining the fate of normal stem cells. Low levels of ROS are required for stem cells to maintain quiescence and self-renewal. Increases in ROS production cause stem cell proliferation/differentiation, senescence, and apoptosis in a dose-dependent manner, leading to their exhaustion. Therefore, the production of ROS in stem cells is tightly regulated to ensure that they have the ability to maintain tissue homeostasis and repair damaged tissues for the life span of an organism. In this chapter, we discuss how the production of ROS in normal stem cells is regulated by various intrinsic and extrinsic factors and how the fate of these cells is altered by the dysregulation of ROS production under various pathological conditions. In addition, the implications of the aberrant production of ROS by tumor stem cells for tumor progression and treatment are also discussed. PMID:24974178

Testosterone, aggression, and territoriality in male Western Screech-owls (Otus kennicottii): results from preliminary experiments

Treesearch

Brian L. Herting; James R. Belthoff

1997-01-01

Using a hormone implant protocol, we created treatment groups in which circulating levels of testosterone (T) were increased, decreased, or maintained at normal levels (controls) in male Western Screech-owls (Otus kennicottii). Owls were exposed to tape-recorded vocalizations of a conspecific, to which territory holders responded with aggression....

Chelation protocols for the elimination and prevention of iron overload in thalassaemia.

PubMed

Kolnagou, Annita; Kontoghiorghes, George John

2018-01-01

Iron overload toxicity is the main cause of mortality and morbidity in thalassaemia patients. The complete elimination and prevention of iron overload is the main aim of chelation therapy, which can be achieved by chelation protocols that can effectively remove excess iron load and maintain body iron at normal levels. Deferiprone and selected combinations with deferoxamine can be designed, adjusted and used effectively for removing all excess stored iron and for maintaining normal iron stores (NIS) in different categories of thalassaemia patients. High doses of deferiprone (75-100 mg/kg/day) and deferoxamine (50-60 mg/kg, 1-7 days/week) combinations can be used for achieving and maintaining NIS in heavily iron loaded transfused patients. In contrast, deferiprone (75-100 mg/kg/day) can be used effectively and sometimes intermittently for maintaining NIS in non heavily transfused patients. Deferasirox can in particular be used in patients not tolerating deferoxamine and deferiprone. The design of tailored made personalised protocols using deferiprone and selected combinations with deferoxamine should be considered as optimum chelation therapies for the complete treatment and the prevention of iron overload in thalassaemia.

40 CFR 265.347 - Monitoring and inspections.

Code of Federal Regulations, 2010 CFR

2010-07-01

... minutes. Appropriate corrections to maintain steady state combustion conditions must be made immediately... would normally include those measuring waste feed, auxiliary fuel feed, air flow, in-ciner-a-tor temperature, scrubber flow, scrubber pH, and relevant level -controls. (b) The complete incinerator and...

Microfabricated Multianalyte Sensor Arrays for Metabolic Monitoring

DTIC Science & Technology

2007-09-01

Introduction Intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range can prevent or delay...the occurrence of diabetic related complications.1 Diabetic patients, therefore, have to frequently monitor their blood glucose levels by drawing... blood necessary for conventional glucose monitoring. The blood data obtained gives no indication of direction or trend of blood sugar levels. Even the

Hypobaric Control of Ethylene-Induced Leaf Senescence in Intact Plants of Phaseolus vulgaris L. 1

PubMed Central

Nilsen, Karl N.; Hodges, Clinton F.

1983-01-01

A controlled atmospheric-environment system (CAES) designed to sustain normal or hypobaric ambient growing conditions was developed, described, and evaluated for its effectiveness as a research tool capable of controlling ethylene-induced leaf senescence in intact plants of Phaseolus vulgaris L. Senescence was prematurely-induced in primary leaves by treatment with 30 parts per million ethephon. Ethephon-derived endogenous ethylene reached peak levels within 6 hours at 26°C. Total endogenous ethylene levels then temporarily stabilized at approximately 1.75 microliters per liter from 6 to 24 hours. Thereafter, a progressive rise in ethylene resulted from leaf tissue metabolism and release. Throughout the study, the endogenous ethylene content of ethephon-treated leaves was greater than that of nontreated leaves. Subjecting ethephon-treated leaves to atmospheres of 200 millibars, with O2 and CO2 compositions set to approximate normal atmospheric partial pressures, prevented chlorophyll loss. Alternately, subjecting ethephon-treated plants to 200 millibars of air only partially prevented chlorophyll loss. Hypobaric conditions (200 millibars), with O2 and CO2 at normal atmospheric availability, could be delayed until 48 hours after ethephon treatment and still prevent most leaf senescence. In conclusion, hypobaric conditions established and maintained within the CAES prevented ethylene-induced senescence (chlorosis) in intact plants, provided O2 and CO2 partial pressures were maintained at levels approximating normal ambient availability. An unexpected increase in endogenous ethylene was detected within nontreated control leaves 48 hours subsequent to relocation from winter greenhouse conditions (latitude, 42°00″ N) to the CAES operating at normal ambient pressure. The longer photoperiod and/or higher temperature utilized within the CAES are hypothesized to influence ethylene metabolism directly and growth-promotive processes (e.g. response thresholds) indirectly. PMID:16662806

Low empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls.

PubMed

Netten, Anouk P; Rieffe, Carolien; Theunissen, Stephanie C P M; Soede, Wim; Dirks, Evelien; Briaire, Jeroen J; Frijns, Johan H M

2015-01-01

The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy. The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children's level of empathy, their attendance to others' emotions, emotion recognition, and supportive behavior. Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children. Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships.

Hypoglycaemia and hypoxic-ischaemic encephalopathy.

PubMed

Boardman, James P; Hawdon, Jane M

2015-04-01

The transition from fetal to neonatal life requires metabolic adaptation to ensure that energy supply to vital organs and systems is maintained after separation from the placental circulation. Under normal conditions, this is achieved through the mobilization and use of alternative cerebral fuels (fatty acids, ketone bodies, and lactate) when blood glucose concentration falls. Severe hypoxia-ischaemia is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions can be harmful in association with hypoxia-ischaemia. The optimal target blood glucose level for ensuring adequate energy provision in hypoxic-ischaemic encephalopathy (HIE) remains unknown. However, recent data support guidance to maintain a blood glucose concentration of 2.5 mmol/L or more in neonates with signs of acute neurological dysfunction, which includes those with HIE, and this is higher than the accepted threshold of 2 mmol/L in infants without signs of neurological dysfunction or hyperinsulinism. © The Authors. Journal compilation © 2015 Mac Keith Press.

Normocalcemia without hyperparathyroidism in vitamin D-deficient rats.

PubMed

Kollenkirchen, U; Fox, J; Walters, M R

1991-03-01

Despite numerous attempts, no reliable dietary regimen exists to achieve vitamin D deficiency (-D) in rats without attendant changes in plasma parathyroid hormone (PTH), Ca, or phosphate. This represents an important obstacle to proper investigations of the physiologic role(s) of vitamin D metabolites in the function of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] target tissues. This paper describes the successful development of such a diet, which uses a combination of high Ca content, properly controlled Ca/P ratio, and lactose. Normal weanling rats were fed diets containing A, 0.8% Ca, 0.5% P, +D3, or -D diets containing B, 0.8% Ca and 0.5% P; C, 2.0% Ca and 1.25% P; or D, 2.0% Ca, 1.25% P, and 20% lactose. After 6 diet weeks group D rats remained normocalcemic and normophosphatemic, but diet groups B and C became hypocalcemic (6.9 +/- 0.8 and 7.2 +/- 0.4 mg/dl, respectively). Thus high dietary Ca and P was incapable of maintaining normal plasma Ca levels in the absence of dietary lactose. The normocalcemia in group D was not maintained by elevated PTH secretion because N-terminal PTH levels were also normal (14 +/- 3 versus 20 +/- 5 pg/ml). In contrast, PTH levels were markedly elevated in hypocalcemic groups B and C (47 +/- 7 and 48 +/- 10 pg/ml, respectively). Plasma 25-OHD3 and 1,25-(OH)2D3 levels were reduced to less than 120 and less than 12 pg/ml, respectively, in all -D groups. Thus the high-Ca diet and the use of normal weanlings did not impede the development of vitamin D deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Numerical Investigation of Hydrogen and Kerosene Combustion in Supersonic Air Streams

NASA Technical Reports Server (NTRS)

Taha, A. A.; Tiwari, S. N.; Mohieldin, T. O.

1999-01-01

The effect of mixing schemes on the combustion of both gaseous hydrogen and liquid kerosene is investigated. Injecting pilot gaseous hydrogen parallel to the supersonic incoming air tends to maintain the stabilization of the main liquid kerosene, which is normally injected. Also the maximum kerosene equivalence ratio that can maintain stable flame can be increased by increasing the pilot energy level. The wedge flame holding contributes to an increased kerosene combustion efficiency by the generation of shock-jet interaction.

Properties of murine embryonic stem cells maintained on human foreskin fibroblasts without LIF.

PubMed

Meng, G L; Zur Nieden, N I; Liu, S Y; Cormier, J T; Kallos, M S; Rancourt, D E

2008-04-01

In embryonic stem (ES) cells, leukemia inhibitory factor (LIF)/STAT3, wnt and nodal/activin signaling are mainly active to control pluripotency during expansion. To maintain pluripotency, ES cells are typically cultured on feeder cells of varying origins. Murine ES cells are commonly cultured on murine embryonic fibroblasts (MEFs), which senesce early and must be frequently prepared. This process is laborious and leads to batch variation presenting a challenge for high-throughput ES cell expansion. Although some cell lines can be sustained by exogenous LIF, this method is costly. We present here a novel and inexpensive culture method for expanding murine ES cells on human foreskin fibroblast (HFF) feeders. After 20 passages on HFFs without LIF, ES cell lines showed normal expression levels of pluripotency markers, maintained a normal karyotype and retained the ability to contribute to the germline. As HFFs do not senesce for at least 62 passages, they present a vast supply of feeders. Copyright 2007 Wiley-Liss, Inc.

Lunar Phase Modulates Circadian Gene Expression Cycles in the Broadcast Spawning Coral Acropora millepora.

PubMed

Brady, Aisling K; Willis, Bette L; Harder, Lawrence D; Vize, Peter D

2016-04-01

Many broadcast spawning corals in multiple reef regions release their gametes with incredible temporal precision just once per year, using the lunar cycle to set the night of spawning. Moonlight, rather than tides or other lunar-regulated processes, is thought to be the proximate factor responsible for linking the night of spawning to the phase of the Moon. We compared patterns of gene expression among colonies of the broadcast spawning coral Acropora millepora at different phases of the lunar cycle, and when they were maintained under one of three experimentally simulated lunar lighting treatments: i) lunar lighting conditions matching those on the reef, or lunar patterns mimicking either ii) constant full Moon conditions, or iii) constant new Moon conditions. Normal lunar illumination was found to shift both the level and timing of clock gene transcription cycles between new and full moons, with the peak hour of expression for a number of genes occurring earlier in the evening under a new Moon when compared to a full Moon. When the normal lunar cycle is replaced with nighttime patterns equivalent to either a full Moon or a new Moon every evening, the normal monthlong changes in the level of expression are destroyed for most genes. In combination, these results indicate that daily changes in moonlight that occur over the lunar cycle are essential for maintaining normal lunar periodicity of clock gene transcription, and this may play a role in regulating spawn timing. These data also show that low levels of light pollution may have an impact on coral biological clocks. © 2016 Marine Biological Laboratory.

Taste Changes in Vitamin A Deficiency

PubMed Central

Bernard, Rudy A.; Halpern, Bruce P.

1968-01-01

Taste preferences were studied in two groups of rats depleted of vitamin A by dietary restriction. One group received sufficient vitamin A acid supplement to maintain normal growth. The other group was repleted with vitamin A alcohol after the classical deficiency symptoms had appeared; this group gradually lost normal preferences for NaCl and aversion to quinine solutions during depletion. Vitamin A alcohol repletion tended to restore taste preferences to normal. In contrast, the group receiving vitamin A acid showed normal taste preferences throughout the depletion period. When the vitamin A acid supplement was removed taste preferences became abnormal and returned to normal when vitamin A acid was restored. Peripheral gustatory neural activity of depleted rats without any form of vitamin A was less than normal both at rest and when the tongue was stimulated with NaCl solutions. Histological examination showed keratin infiltrating the pores of the taste buds. Accessory glandular tissues were atrophied and debris filled the trenches of the papillae. It is concluded that vitamin A acid can provide the vitamin A required for normal taste, as contrasted with its inability to maintain visual function. It is suggested that the effect of vitamin A is exerted at the receptor level, as a result of its role in the biosynthesis of mucopolysaccharides, which have been recently identified in the pore area of taste buds, as well as being present in the various secretions of the oral cavity. PMID:4299794

Vitamin D deficiency in multiple sclerosis: Should testing and treatment be based on racial background?

PubMed

Avasarala, Jagannadha; Zachariah, Phenu

2015-11-15

Maintaining adequate levels of vitamin D may have a protective effect and lower the risk of multiple sclerosis (MS). For patients with MS, maintaining an adequate level of vitamin D level is probably associated with lessening of the frequency and severity of their symptoms. However, what remains unclear is whether if this is true across all racial/ethnic backgrounds. In African-Americans (AAs) this effect is not only absent but curiously enough, low levels of vitamin D do not matter since the bioavailability of this molecule in AA subjects is normal. It is this paradox that led to this brief report and we suggest more research and database construction based on race/ethnicity be done, as a first step to understand the biological mechanisms that confer or negate the effect of vitamin D levels in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

29 CFR 1926.303 - Abrasive wheels and tools.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and tools. (a) Power. All grinding machines shall be supplied with sufficient power to maintain the spindle speed at safe levels under all conditions of normal operation. (b) Guarding. (1) Grinding machines..., nut, and outer flange may be exposed on machines designed as portable saws. (c) Use of abrasive wheels...

29 CFR 1926.303 - Abrasive wheels and tools.

Code of Federal Regulations, 2014 CFR

2014-07-01

... and tools. (a) Power. All grinding machines shall be supplied with sufficient power to maintain the spindle speed at safe levels under all conditions of normal operation. (b) Guarding. (1) Grinding machines..., nut, and outer flange may be exposed on machines designed as portable saws. (c) Use of abrasive wheels...

29 CFR 1926.303 - Abrasive wheels and tools.

Code of Federal Regulations, 2012 CFR

2012-07-01

... and tools. (a) Power. All grinding machines shall be supplied with sufficient power to maintain the spindle speed at safe levels under all conditions of normal operation. (b) Guarding. (1) Grinding machines..., nut, and outer flange may be exposed on machines designed as portable saws. (c) Use of abrasive wheels...

10 CFR 36.33 - Irradiator pools.

Code of Federal Regulations, 2013 CFR

2013-01-01

... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5 meter...

10 CFR 36.33 - Irradiator pools.

Code of Federal Regulations, 2010 CFR

2010-01-01

... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5 meter...

10 CFR 36.33 - Irradiator pools.

Code of Federal Regulations, 2011 CFR

2011-01-01

... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5 meter...

10 CFR 36.33 - Irradiator pools.

Code of Federal Regulations, 2014 CFR

2014-01-01

... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5 meter...

10 CFR 36.33 - Irradiator pools.

Code of Federal Regulations, 2012 CFR

2012-01-01

... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5 meter...

Low Empathy in Deaf and Hard of Hearing (Pre)Adolescents Compared to Normal Hearing Controls

PubMed Central

Netten, Anouk P.; Rieffe, Carolien; Theunissen, Stephanie C. P. M.; Soede, Wim; Dirks, Evelien; Briaire, Jeroen J.; Frijns, Johan H. M.

2015-01-01

Objective The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy. Methods The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children’s level of empathy, their attendance to others’ emotions, emotion recognition, and supportive behavior. Results Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children. Conclusions Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships. PMID:25906365

Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells.

PubMed

Ke, Jia; Zhao, Zhiju; Hong, Su-Hyung; Bai, Shoumin; He, Zhen; Malik, Fayaz; Xu, Jiahui; Zhou, Lei; Chen, Weilong; Martin-Trevino, Rachel; Wu, Xiaojian; Lan, Ping; Yi, Yongju; Ginestier, Christophe; Ibarra, Ingrid; Shang, Li; McDermott, Sean; Luther, Tahra; Clouthier, Shawn G; Wicha, Max S; Liu, Suling

2015-02-28

Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium.

Objective Evaluation of Vergence Disorders and a Research-Based Novel Method for Vergence Rehabilitation

PubMed Central

Kapoula, Zoï; Morize, Aurélien; Daniel, François; Jonqua, Fabienne; Orssaud, Christophe; Brémond-Gignac, Dominique

2016-01-01

Purpose We performed video-oculography to evaluate vergence eye movement abnormalities in students diagnosed clinically with vergence disorders. We tested the efficiency of a novel rehabilitation method and evaluated its benefits with video-oculography cross-correlated with clinical tests and symptomatology. Methods A total of 19 students (20–27 years old) underwent ophthalmologic, orthoptic examination, and a vergence test coupled with video-oculography. Eight patients were diagnosed with vergence disorders with a high symptomatology score (CISS) and performed a 5-week session of vergence rehabilitation. Vergence and rehabilitation tasks were performed with a trapezoid surface of light emitting diodes (LEDs) and adjacent buzzers (US 8851669). We used a novel Vergence double-step (Vd-s) protocol: the target stepped to a second position before the vergence movement completion. Afterward the vergence test was repeated 1 week and 1 month later. Results Abnormally increased intertrial variability was observed for many vergence parameters (gain, duration, and speed) for the subjects with vergence disorders. High CISS scores were correlated with variability and increased latency. After the Vd-s, variability of all parameters dropped to normal or better levels. Moreover, the convergence and divergence latency diminished significantly to levels better than normal; benefits were maintained 1 month after completion of Vd-s. CISS scores dropped to normal level, which was maintained up to 1 year. Conclusions and Translational Relevance: Intertrial variability is the major marker of vergence disorders. The Vd-s research-based method leads to normalization of vergence properties and lasting removal of symptoms. The efficiency of the method is due to the spatiotemporal parameters of repetitive trials that stimulate neural plasticity. PMID:26981330

Effects of illumination on human nocturnal serum melatonin levels and performance

NASA Technical Reports Server (NTRS)

Dollins, A. B.; Lynch, H. J.; Wurtman, R. J.; Deng, M. H.; Lieberman, H. R.

1993-01-01

In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36) = 12.77, p < 0.001, in a dose-dependent manner. Performance on vigilance, reaction time, and other tasks deteriorated throughout the night, consistent with known circadian variations in these parameters, but independent of ambient light intensity and circulating melatonin levels.

Psychotherapy for Some Anxiety Sequelae of Leukemia.

ERIC Educational Resources Information Center

Stokes, Trevor

1999-01-01

This case study describes use of a program of self-mediated recording and intervention, including distraction techniques, with monitoring within the family, with an 8-year-old child with leukemia and a generalized anxiety about health. Anxiety was reduced to the normal range and maintained at that level at a nine-month followup assessment.…

Shock wave absorber having apertured plate

DOEpatents

Shin, Y.W.; Wiedermann, A.H.; Ockert, C.E.

1983-08-26

The shock or energy absorber disclosed herein utilizes an apertured plate maintained under the normal level of liquid flowing in a piping system and disposed between the normal liquid flow path and a cavity pressurized with a compressible gas. The degree of openness (or porosity) of the plate is between 0.01 and 0.60. The energy level of a shock wave travelling down the piping system thus is dissipated by some of the liquid being jetted through the apertured plate toward the cavity. The cavity is large compared to the quantity of liquid jetted through the apertured plate, so there is little change in its volume. The porosity of the apertured plate influences the percentage of energy absorbed.

Shock wave absorber having apertured plate

DOEpatents

Shin, Yong W.; Wiedermann, Arne H.; Ockert, Carl E.

1985-01-01

The shock or energy absorber disclosed herein utilizes an apertured plate maintained under the normal level of liquid flowing in a piping system and disposed between the normal liquid flow path and a cavity pressurized with a compressible gas. The degree of openness (or porosity) of the plate is between 0.01 and 0.60. The energy level of a shock wave travelling down the piping system thus is dissipated by some of the liquid being jetted through the apertured plate toward the cavity. The cavity is large compared to the quantity of liquid jetted through the apertured plate, so there is little change in its volume. The porosity of the apertured plate influences the percentage of energy absorbed.

Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

PubMed

Marwali, Eva M; Boom, Cindy E; Sakidjan, Indriwanto; Santoso, Anwar; Fakhri, Dicky; Kartini, Ay; Kekalih, Aria; Schwartz, Steven M; Haas, Nikolaus A

2013-09-01

This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p < 0.01]; free triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p < 0.01]). There was no evidence of hyperthyroidism or suppression of the pituitary-thyroid axis in either treatment group Oral triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

Establishment of ultra long-lived cell lines by transfection of TERT into normal human fibroblast TIG-1 and their characterization.

PubMed

Kamada, Mizuna; Kumazaki, Tsutomu; Matsuo, Taira; Mitsui, Youji; Takahashi, Tomoko

2012-06-01

To establish useful human normal cell lines, TERT (telomerase reverse transcriptase) cDNA was transfected into normal female lung fibroblast, TIG-1. After long-term-sub-cultivation of 74 individual clones selected for resistance to G418, we obtained 55 cultures with normal range of life span [75 PDL (population doubling level)], 16 cultures with extended life span (75-140 PDL). In addition, 3 immortal cell strains and unexpectedly, one ultra long-lived cell line (ULT-1) with life span of 166 PDL were established. IMT-1, one of the immortal cell strains was confirmed to maintain long telomere length, high telomerase activity and an extremely low level of p16INK4A. They also showed moderate p53 and p21CIP1 expression, keeping vigorous growth rate even at 450 PDL. High level of fibronectin and collagen 1α expression confirmed IMT-1 as normal fibroblasts, although one X chromosome had been lost. ULT-1, however, kept a near normal karyotypes and had shortening of telomere length, high expression of p16INK4A, moderate levels of senescence associated-β-galactosidase positive cells and decreased growth rate only after 150 PDs (population doublings), and finally reached senescence at 166 PDL with morphology of normal senescent fibroblasts. As resources of standard normal human cell, abundant vials of early and middle passages of ULT-1 have been stocked. The use of the cell line is discussed, focusing on isograft of artificial skin and screening of anti-aging or safe chemical agents.

Low plasma PDGF-BB levels are associated with estradiol in postmenopausal osteoporosis: PDGF-BB mediated by estradiol in women.

PubMed

Tang, Lanhua; Xia, Zhuying; Luo, Zhongwei; Long, Haitao; Zhu, Yong; Zhao, Shushan

2017-08-01

Objective This study aimed to investigate the association between low plasma Platelet-derived growth factor-BB (PDGF-BB) levels and oestradiol in Postmenopausal osteoporosis (PMOP). Methods This prospective study measured plasma PDGF-BB and oestradiol levels in outpatients who were admitted to our hospital. Participants were screened and then allocated to three groups: normal young women, postmenopausal control, and PMOP. Additionally, Sprague-Dawley rats underwent either sham surgery or bilateral ovariectomy (OVX), and were divided into the following groups: sham, OVX, OVX + oestradiol, and OVX + PDGF-BB. Plasma oestradiol and PDGF-BB levels were measured using commercially available ELISA kits. Results A total of 121 participants, including 69 normal young women, 28 patients with primary PMOP, and 24 age-matched postmenopausal women were enrolled. Plasma oestradiol and PDGF-BB levels were lower in postmenopausal women, especially in PMOP ( P < 0.01). Pearson correlations analysis showed that PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age ( P < 0.01). The OVX rat model showed that oestradiol replacement increased plasma PDGF-BB levels, while PDGF-BB systematic treatment had no effect on plasma oestradiol levels. Conclusions Plasma PDGF-BB levels are maintained by oestrogen in normal young women and play a major role in PMOP.

Regulation of Synaptic Structure by the Ubiquitin C-terminal Hydrolase UCH-L1

PubMed Central

Cartier, Anna E.; Djakovic, Stevan N.; Salehi, Afshin; Wilson, Scott M.; Masliah, Eliezer; Patrick, Gentry N.

2009-01-01

UCH-L1 is a de-ubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We have found that UCH-L1 activity is rapidly up-regulated by NMDA receptor activation which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of pre and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1 inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner. PMID:19535597

Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.

PubMed

Cartier, Anna E; Djakovic, Stevan N; Salehi, Afshin; Wilson, Scott M; Masliah, Eliezer; Patrick, Gentry N

2009-06-17

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

Nucleoprotein Changes in Plant Tumor Growth

PubMed Central

Rasch, Ellen; Swift, Hewson; Klein, Richard M.

1959-01-01

Tumor cell transformation and growth were studied in a plant neoplasm, crown gall of bean, induced by Agrobacterium rubi. Ribose nucleic acid (RNA), deoxyribose nucleic acid (DNA), histone, and total protein were estimated by microphotometry of nuclei, nucleoli, and cytoplasm in stained tissue sections. Transformation of normal cells to tumor cells was accompanied by marked increases in ribonucleoprotein content of affected tissues, reaching a maximum 2 to 3 days after inoculation with virulent bacteria. Increased DNA levels were in part associated with increased mitotic frequency, but also with progressive accumulation of nuclei in the higher DNA classes, formed by repeated DNA doubling without intervening reduction by mitosis. Some normal nuclei of the higher DNA classes (with 2, 4, or 8 times the DNA content of diploid nuclei) were reduced to diploid levels by successive cell divisions without intervening DNA synthesis. The normal relation between DNA synthesis and mitosis was thus disrupted in tumor tissue. Nevertheless, clearly defined DNA classes, as found in homologous normal tissues, were maintained in the tumor at all times. PMID:13673042

Use of liothyronine without levothyroxine in the treatment of mild consumptive hypothyroidism caused by hepatic hemangiomas.

PubMed

Higuchi, Shinji; Takagi, Masaki; Hasegawa, Yukihiro

2017-06-29

There have been reports of the use of levothyroxine or levothyroxine plus liothyronine for consumptive hypothyroidism caused by hepatic hemangiomas. Administration of levothyroxine without liothyronine can be inadequate to maintain normal levels of both free T3 and free T4 in some patients. However, there is no report of treatment with liothyronine plus propranolol. We herein present a case in which we used liothyronine therapy for multifocal hepatic hemangiomas in a Japanese patient with low free T3 and normal free T4 levels. A 2-month-old Japanese male was referred to our hospital because of jaundice. Abdominal computed tomography showed multifocal hemangiomas in both lobes of the liver. TSH level was elevated, free T3 level was low, free T4 level was normal, and hypothyroidism due to hepatic hemangiomas was diagnosed. In addition to propranolol, liothyronine was started. We used liothyronine without levothyroxine for hypothyroidism because only free T3 level had decreased, whereas free T4 level remained in the normal range. The TSH and free T3 levels normalized in this patient in less than 1 month. The liothyronine dose was gradually reduced with regression of the hemangiomas, and liothyronine administration was discontinued at the age of 5 months. At the age of 11 months, growth and neurological development of the patient met age-specific norms, and he was euthyroid at that time. This is the first report demonstrating the use of liothyronine with propranolol for treatment of this type of consumptive hypothyroidism.

Asymptomatic Child Heterozygous for Hemoglobin S and Hemoglobin Pôrto Alegre

PubMed Central

Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

2013-01-01

Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser→Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation. PMID:21225927

Normal peer models and autistic children's learning.

PubMed Central

Egel, A L; Richman, G S; Koegel, R L

1981-01-01

Present research and legislation regarding mainstreaming autistic children into normal classrooms have raised the importance of studying whether autistic children can benefit from observing normal peer models. The present investigation systematically assessed whether autistic children's learning of discrimination tasks could be improved if they observed normal children perform the tasks correctly. In the context of a multiple baseline design, four autistic children worked on five discrimination tasks that their teachers reported were posing difficulty. Throughout the baseline condition the children evidenced very low levels of correct responding on all five tasks. In the subsequent treatment condition, when normal peers modeled correct responses, the autistic children's correct responding increased dramatically. In each case, the peer modeling procedure produced rapid achievement of the acquisition which was maintained after the peer models were removed. These results are discussed in relation to issues concerning observational learning and in relation to the implications for mainstreaming autistic children into normal classrooms. PMID:7216930

Kinematical Comparison of the 200 m Backstroke Turns between National and Regional Level Swimmers

PubMed Central

Veiga, Santiago; Cala, Antonio; Frutos, Pablo González; Navarro, Enrique

2013-01-01

The aims of this investigation were to determine the evolution of selected turn variables during competitive backstroke races and to compare these kinematic variables between two different levels of swimmers. Sixteen national and regional level male swimmers participant in the 200 m backstroke event at the Spanish Swimming Championships in short course (25 m) were selected to analyze their turn performances. The individual distances method with two-dimensional Direct Linear Transformation (2D-DLT) algorithms was used to perform race analyses. National level swimmers presented a shorter “turn time”, a longer “distance in”, a faster “underwater velocity” and “normalized underwater velocity”, and a faster “stroking velocity” than regional level swimmers, whereas no significant differences were detected between levels for the “underwater distance”. National level swimmers maintained similar “turn times” over the event and increased “underwater velocity” and “normalized underwater velocity” in the last (seventh) turn segment, whereas regional level swimmers increased “turn time” in the last half of the race. For both national and regional level swimmers, turn “underwater distance” during the last three turns of the race was significantly shorter while no significant differences in distance into the wall occurred throughout the race. The skill level of the swimmers has an impact on the competitive backstroke turn segments. In a 200 m event, the underwater velocity should be maximized to maintain turn proficiency, whereas turn distance must be subordinated to the average velocity. Key Points The underwater turn velocity is as a critical variable related to the swimmers’ level of skill in a 200 m backstroke event. Best swimmers perform faster but no longer turn segments during a 200 m backstroke event. Best swimmers maintain their turn performance throughout the 200 m backstroke event by increasing the underwater velocity during the final part of the race. The turn distance out seems to be subordinated in order to maximize the average velocity during a 200 m backstroke event. PMID:24421733

Differential effects of cyclic and constant stress on ATP release and mucociliary transport by human airway epithelia

PubMed Central

Button, Brian; Picher, Maryse; Boucher, Richard C

2007-01-01

In the lungs, the first line of defence against bacterial infection is the thin layer of airway surface liquid (ASL) lining the airway surface. The superficial airway epithelium exhibits complex regulatory pathways that blend ion transport to adjust ASL volume to maintain proper mucociliary clearance (MCC). We hypothesized that stresses generated by airflow and transmural pressures during breathing govern ASL volume by regulating the rate of epithelial ATP release. Luminal ATP, via interactions with apical membrane P2-purinoceptors, regulates the balance of active ion secretion versus absorption to maintain ASL volume at optimal levels for MCC. In this study we tested the hypothesis that cyclic compressive stress (CCS), mimicking normal tidal breathing, regulates ASL volume in airway epithelia. Polarized tracheobronchial epithelial cultures from normal and cystic fibrosis (CF) subjects responded to a range of CCS by increasing the rate of ATP release. In normal airway epithelia, the CCS-induced increase in ASL ATP concentration was sufficient to induce purinoceptor-mediated increases in ASL height and MCC, via inhibition of epithelial Na+-channel-mediated Na+ absorption and stimulation of Cl− secretion through CFTR and the Ca2+-activated chloride channels. In contrast, static, non-oscillatory stress did not stimulate ATP release, ion transport or MCC, emphasizing the importance of rhythmic mechanical stress for airway defence. In CF airway cultures, which exhibit basal ASL depletion, CCS was partially effective, producing less ASL volume secretion than in normal cultures, but a level sufficient to restore MCC. The present data suggest that CCS may (1) regulate ASL volume in the normal lung and (2) improve clearance in the lungs of CF patients, potentially explaining the beneficial role of exercise in lung defence. PMID:17317749

Long-Term Weight Maintenance Strategies Are Experienced as a Burden by Persons Who Have Lost Weight Compared to Persons with a lifetime Normal, Stable Weight.

PubMed

Kruseman, Maaike; Schmutz, Noémi; Carrard, Isabelle

2017-01-01

To assess dietary intake, eating patterns, physical activity and eating behaviors, and to explore strategies and perceptions of the experience of weight maintenance in weight loss maintainers (weight loss maintenance (WLM) ≥ 10% weight loss maintained for ≥1 year) and in matched controls with a lifetime stable normal weight. Volunteers (32) were recruited by a snowball procedure in this cross-sectional, mixed-methods study. Diet, physical activity, and eating behaviors were assessed with validated questionnaires. Strategies and experiences were investigated during interviews. Descriptive coding, thematic analysis (qualitative data) as well as descriptive analysis and t-tests (quantitative data) were performed. Both groups had similar energy and macronutrient consumption. Those in the WLM group reported higher levels of exercise and scored higher on several dimensions of eating disorders. Four themes - 'food choices,' 'quantities and portion control,' 'physical activity', and 'burden' - emerged from the qualitative data. Both groups used similar weight maintenance strategies, but those in the WLM group experienced a higher burden, expressing effortful control which contrasted with the control group's confidence in their internal cues. Our results show an additional burden related with maintaining weight loss compared to keeping a stable normal weight. They provide evidence to devise interventions that will address the difficulty of regulating intake. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Transient ventricular dysfunction after an asphyxiation event: stress or hypoxia?

PubMed

Valletta, Mary E; Haque, Ikram; Al-Mousily, Faris; Udassi, Jai; Saidi, Arwa

2008-11-01

This report of a pediatric patient with acute upper airway obstruction causing asphyxiation emphasizes the need to maintain clinical suspicion for acquired myocardial dysfunction, despite the presumed role of noncardiogenic causes for pulmonary edema after an acute upper airway obstruction. Case report. A tertiary pediatric intensive care unit. A 10-year-old girl with no significant medical history who developed flash pulmonary edema and acute myocardial dysfunction after an acute upper airway obstruction. Serial echocardiograms, exercise stress test, and coronary angiography were performed. Serial pro-brain natriuretic peptide, troponins, and CK-MB levels were also followed. Troponin level normalized approximately 7 days after the acute event. CK-MB and pro-brain natriuretic peptide levels decreased but had not completely normalized by time of discharge. The patient was discharged home 10 days after the event on an anticipated 6-month course of metoprolol without any signs or symptoms of cardiac dysfunction. Myocardial dysfunction is rarely documented in children after an acute upper airway obstruction or an asphyxiation event. Pediatric intensivists and hospitalists should maintain a high degree of clinical suspicion and screen for possible myocardial dysfunction in the pediatric patient with an acute severe hypoxic event especially when accompanied by pulmonary edema. Prompt evaluation ensures appropriate support. Additionally, some role may exist for early adrenergic receptor blockade.

Level-dependent changes in detection of temporal gaps in noise markers by adults with normal and impaired hearing

PubMed Central

Horwitz, Amy R.; Ahlstrom, Jayne B.; Dubno, Judy R.

2011-01-01

Compression in the basilar-membrane input–output response flattens the temporal envelope of a fluctuating signal when more gain is applied to lower level than higher level temporal components. As a result, level-dependent changes in gap detection for signals with different depths of envelope fluctuation and for subjects with normal and impaired hearing may reveal effects of compression. To test these assumptions, gap detection with and without a broadband noise was measured with 1 000-Hz-wide (flatter) and 50-Hz-wide (fluctuating) noise markers as a function of marker level. As marker level increased, background level also increased, maintaining a fixed acoustic signal-to-noise ratio (SNR) to minimize sensation-level effects on gap detection. Significant level-dependent changes in gap detection were observed, consistent with effects of cochlear compression. For the flatter marker, gap detection that declines with increases in level up to mid levels and improves with further increases in level may be explained by an effective flattening of the temporal envelope at mid levels, where compression effects are expected to be strongest. A flatter effective temporal envelope corresponds to a reduced effective SNR. The effects of a reduction in compression (resulting in larger effective SNRs) may contribute to better-than-normal gap detection observed for some hearing-impaired listeners. PMID:22087921

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessment of the maximum voluntary arm muscle contraction in sign language for the deaf.

PubMed

Regalo, S C H; Teixeira, V R; Vitti, M; Chaves, T C; Hallak, J E C; Bevilaqua-Grossi, D; Siriani de Oliveira, A

2006-01-01

The purpose of this study was to investigate the levels of upper member muscles' activation of deaf individuals, who use the Brazilian sign language - LIBRAS, comparing these findings to volunteers with no postural deviations and normal hearing Forty eight volunteers divided into two groups comprising healthy and deaf subjects (24 volunteers for each group). The signs of rest were obtained with the volunteer maintaining the upper member in an anatomical position, but with the forearm flexed and sustained by the lower member. Maximum voluntary isometric contractions (MVIC) of the biceps, triceps, deltoid, and trapezius muscles were performed in the position of muscular function testing. Statistical analysis was performed using the SPSS-10.0. Continuous data with normal distribution were analyzed by ANOVA with the significance level of p < 0.01. The normalized electromyographic muscle data obtained in muscular rest do not show statistically significant differences among the studies muscles, in both groups. In the comparison of normalized RMS values obtained in MVIC, the mean values for the trapezius muscle of deaf group were statistically lower than control group. This study's results indicate there are no differences between the levels of muscular activation for arm biceps, arm triceps, and the anterior portion of the deltoid muscle between the mean normalized RMS values of deaf and healthy individuals.

Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition.

PubMed

Ragland, J Daniel; Gur, Ruben C; Valdez, Jeffrey N; Loughead, James; Elliott, Mark; Kohler, Christian; Kanes, Stephen; Siegel, Steven J; Moelter, Stephen T; Gur, Raquel E

2005-10-01

Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies.

Molecular Pathophysiology of Hepatic Glucose Production

PubMed Central

Sharabi, Kfir; Tavares, Clint D. J.; Rines, Amy K.; Puigserver, Pere

2015-01-01

Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycaemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM. PMID:26549348

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum

PubMed Central

Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde

2017-01-01

Background Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. Method The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. Results At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. Conclusion The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period. PMID:29176762

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum.

PubMed

Sanda, Birgitte; Vistad, Ingvild; Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde; Torstveit, Monica Klungland

2017-01-01

Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period.

A Probable Endocrine Basis for the Depression of Ketone Bodies during Infectious or Inflammatory State in Rats

DTIC Science & Technology

1980-01-01

were maintained on a commerciel diet -- nals," as promulgated by the Committee on Care and Use of (Wayne Lab-Blox, Allied Mills, Inc., Chicago, IL...on the level of plasma insulin in the hypo . host. Instead, a decrease has been observed. At the physectomized (A) and normal rats. The level of...Recent data (27) have indicated that during caloric Vaughn. The authors also thank Mrs. Rebecca Arnold for her skilled deprivation associated with severe

Plasticity in the Developing Brain: Intellectual, Language and Academic Functions in Children with Ischaemic Perinatal Stroke

ERIC Educational Resources Information Center

Ballantyne, Angela O.; Spilkin, Amy M.; Hesselink, John; Trauner, Doris A.

2008-01-01

The developing brain has the capacity for a great deal of plasticity. A number of investigators have demonstrated that intellectual and language skills may be in the normal range in children following unilateral perinatal stroke. Questions have been raised, however, about whether these skills can be maintained at the same level as the brain…

Sending Learning Pills to Mobile Devices in Class to Enhance Student Performance and Motivation in Network Services Configuration Courses

ERIC Educational Resources Information Center

Munoz-Organero, M.; Munoz-Merino, P. J.; Kloos, C. D.

2012-01-01

Teaching electrical and computer software engineers how to configure network services normally requires the detailed presentation of many configuration commands and their numerous parameters. Students tend to find it difficult to maintain acceptable levels of motivation. In many cases, this results in their not attending classes and not dedicating…

"Exercise Dependence"--A Problem or Natural Result of High Activity?

ERIC Educational Resources Information Center

Phelan, Suzanne; Bond, Dale S.; Lang, Wei; Jordan, Dustin; Wing, Rena R.

2011-01-01

Objectives: To compare physical activity (PA) and exercise dependence (ED) in 267 weight-loss maintainers (WLM) and 213 normal-weight (NW) controls. Methods: PA and ED assessed via accelerometery and the Exercise Dependence Questionnaire. Results: WLM had higher PA levels and ED scores than those of NW (P less than 0.0001). WLM status (P = 0.006)…

Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice.

PubMed

Liu, Jun-Li; Coschigano, Karen T; Robertson, Katie; Lipsett, Mark; Guo, Yubin; Kopchick, John J; Kumar, Ujendra; Liu, Ye Lauren

2004-09-01

Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR(-/-) mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR(-/-) mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR(-/-) mice was only one-third of that in wild-type littermates. Total beta-cell mass was reduced 4.5-fold in GHR(-/-) mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.

A comparison of preoperative and postoperative nutritional states of lung transplant recipients.

PubMed

Madill, J; Maurer, J R; de Hoyos, A

1993-08-01

Malnutrition is a documented problem in some types of endstage lung disease (ESLD). Recently, isolated lung transplants have successfully reversed the respiratory failure of patients suffering from ESLD. In this study, we compare the preoperative and postoperative nutritional states of lung transplant recipients using weight-to-height ratios, anthropometric measurements, subjective global assessment, and biochemical blood values. Patients with emphysema, cystic fibrosis, and other types of bronchiectasis, but not patients with pulmonary fibrosis or pulmonary hypertension, were malnourished preoperatively. All groups had normal biochemical profiles. Caloric intake of patients with cystic fibrosis and bronchiectasis was increased above predicted basal energy expenditure levels. By six months to one year postoperatively, all groups of malnourished patients had significantly improved their nutritional status. Emphysema patients improved nutrition by maintaining preoperative caloric intake levels--however, both cystic fibrosis and bronchiectasis patients were able to achieve the same goal with significantly decreased caloric intakes. We conclude that malnourished ESLD patients receiving isolated lung grafts are able to achieve normal nutrition within one year posttransplant. Since this occurs in all cases with a reduced, or at best maintained, caloric intake, more study is needed to elucidate the factors that contribute to ESLD malnutrition.

Quantitative Biology of Exercise-Induced Signal Transduction Pathways.

PubMed

Liu, Timon Cheng-Yi; Liu, Gang; Hu, Shao-Juan; Zhu, Ling; Yang, Xiang-Bo; Zhang, Quan-Guang

2017-01-01

Exercise is essential in regulating energy metabolism. Exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation. Among them, endurance/strength training of an individual has been shown to activate its respective signal transduction pathways in skeletal muscle. This was further studied from the viewpoint of quantitative difference (QD). For the mean values, [Formula: see text], of two sets of data, their QD is defined as [Formula: see text] ([Formula: see text]). The function-specific homeostasis (FSH) of a function of a biosystem is a negative-feedback response of the biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in/far from its FSH is called a normal/dysfunctional function. A cellular normal function can resist the activation of other signal transduction pathways so that there are normal function-specific signal transduction pathways which full activation maintains the normal function. An acute endurance/strength training may be dysfunctional, but its regular training may be normal. The normal endurance/strength training of an individual may resist the activation of other signal transduction pathways in skeletal muscle so that there may be normal endurance/strength training-specific signal transduction pathways (NEPs/NSPs) in skeletal muscle. The endurance/strength training may activate NSPs/NEPs, but the QD from the control is smaller than 0.80. The simultaneous activation of both NSPs and NEPs may enhance their respective activation, and the QD from the control is larger than 0.80. The low level laser irradiation pretreatment of rats may promote the activation of NSPs in endurance training skeletal muscle. There may be NEPs/NSPs in skeletal muscle trained by normal endurance/strength training.

Asymptomatic child heterozygous for hemoglobin S and hemoglobin Pôrto Alegre.

PubMed

Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

2011-03-01

Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser → Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation. Copyright © 2010 Wiley-Liss, Inc.

The impact of acute lymphocytic leukemia on diabetic retinopathy.

PubMed

Melberg, N S; Grand, M G; Rup, D

1995-02-01

A 16 year-old girl with a 9-year history of insulin-dependent diabetes mellitus developed acute lymphocytic leukemia. The patient's vision deteriorated from normal to legal blindness within 6 months as her ophthalmologic examination progressed from minimal background diabetic retinopathy to severe proliferative diabetic retinopathy. The accelerated course of diabetic eye disease is attributable to the moderate anemia resulting from the leukemia and its treatment. Although anemia is usually well tolerated by young patients, it is not well tolerated by the diabetic retina. Diabetic patients require close ophthalmologic follow-up and aggressive management to maintain normal hemoglobin levels.

Normalization as a Strategy for Maintaining Quality of Life While Coping with Infertility in a Pronatalist Culture.

PubMed

Benyamini, Yael; Gozlan, Miri; Weissman, Ariel

2017-12-01

Infertility could be highly stressful, particularly in a pronatalist culture. We aimed to develop the concept and a measure of normalization (maintaining normal life routines and feeling "normal") as a strategy that could enable women with infertility maintain their quality of life (QoL) while coping with this condition. We tested its associations with women's well-being, distress and QoL in Israel, where being childless is socially unacceptable and highly stigmatized. One-hundred and eighty Israeli women undergoing infertility treatment at a fertility community clinic filled in questionnaires assessing normalization-related coping strategies, QoL, and psychological adjustment (distress, wellbeing). Eight months later, 55 women conceived; 55 women who had not conceived completed a second questionnaire. At baseline, normalization was related to higher QoL and better adjustment. Structural equation modeling showed that QoL was impaired mainly among women who felt different than others, compared, and blamed themselves. Over time, normalization was overall unrelated to conception or to changes in adjustment yet was protective against decrease in well-being among women who already had a child. Infertility is highly stressful in a pronatalist culture like Israel. It requires treatment yet is not disabling. Patients who manage to maintain normal routines and not feel different than other people their age may experience better QoL and psychological adjustment.

Planning strategies for development of effective exercise and nutrition countermeasures for long-duration space flight

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

2002-01-01

Exercise and nutrition represent primary countermeasures used during space flight to maintain or restore maximal aerobic capacity, musculoskeletal structure, and orthostatic function. However, no single exercise, dietary regimen, or combination of prescriptions has proven entirely effective in maintaining or restoring cardiovascular and musculoskeletal functions to preflight levels after prolonged space flight. As human space flight exposures increase in duration, identification, assessment, and development of various effective exercise- and nutrition-based protective procedures will become paramount. The application of adequate dietary intake in combination with effective exercise prescription will be based on identification of basic physiologic stimuli that maintain normal function in terrestrial gravity, and understanding how specific combinations of exercise characteristics (e.g., duration, frequency, intensity, and mode) can be combined with minimal nutritional requirements that mimic the stimuli normally produced by living in Earth's gravity environment. This can be accomplished only with greater emphasis of research on ground-based experiments targeted at understanding the interactions between caloric intake and expenditure during space flight. Future strategies for application of nutrition and exercise countermeasures for long-duration space missions must be directed to minimizing crew time and the impact on life-support resources.

Matrix remodeling maintains ESC self-renewal by activating Stat3

PubMed Central

Przybyla, Laralynne M.; Theunissen, Thorold W.; Jaenisch, Rudolf; Voldman, Joel

2013-01-01

While a variety of natural and synthetic matrices have been used to influence embryonic stem cell (ESC) self-renewal or differentiation, and ESCs also deposit a rich matrix of their own, the mechanisms behind how extracellular matrix affects cell fate are largely unexplored. The ESC matrix is continuously remodeled by matrix metalloproteinases (MMPs), a process that we find is enhanced by the presence of mouse embryonic fibroblast feeders in a paracrine manner. Matrix remodeling by MMPs aids in the self-renewal of ESCs, as inhibition of MMPs inhibits the ability of ESCs to self-renew. We also find that addition of the interstitial collagenase MMP1 is sufficient to maintain long-term LIF-independent mESC self-renewal in a dose-dependent manner. This remarkable ability is due to the presence of endogenously produced self-renewal-inducing signals, including the LIF-family ligand CNTF, that are normally trapped within the ECM and become exposed upon MMP-induced matrix remodeling to signal through JAK and Stat3. These results uncover a new role for feeder cells in maintaining self-renewal and show that mESCs normally produce sufficient levels of autocrine-acting pro-self-renewal ligands. PMID:23404867

Planning strategies for development of effective exercise and nutrition countermeasures for long-duration space flight.

PubMed

Convertino, Victor A

2002-10-01

Exercise and nutrition represent primary countermeasures used during space flight to maintain or restore maximal aerobic capacity, musculoskeletal structure, and orthostatic function. However, no single exercise, dietary regimen, or combination of prescriptions has proven entirely effective in maintaining or restoring cardiovascular and musculoskeletal functions to preflight levels after prolonged space flight. As human space flight exposures increase in duration, identification, assessment, and development of various effective exercise- and nutrition-based protective procedures will become paramount. The application of adequate dietary intake in combination with effective exercise prescription will be based on identification of basic physiologic stimuli that maintain normal function in terrestrial gravity, and understanding how specific combinations of exercise characteristics (e.g., duration, frequency, intensity, and mode) can be combined with minimal nutritional requirements that mimic the stimuli normally produced by living in Earth's gravity environment. This can be accomplished only with greater emphasis of research on ground-based experiments targeted at understanding the interactions between caloric intake and expenditure during space flight. Future strategies for application of nutrition and exercise countermeasures for long-duration space missions must be directed to minimizing crew time and the impact on life-support resources.

Sequential monitoring and stability of ex vivo-expanded autologous and non-autologous regulatory T cells following infusion in non-human primates

PubMed Central

Zhang, H.; Guo, H.; Lu, L.; Zahorchak, A. F.; Wiseman, R. W.; Raimondi, G.; Cooper, D. K. C.; Ezzelarab, M. B.; Thomson, A. W.

2016-01-01

Ex vivo-expanded cynomolgus monkey CD4+CD25+CD127− regulatory T cells (Treg) maintained Foxp3 demethylation status at the Treg-Specific Demethylation Region (TSDR), and potently suppressed T cell proliferation through 3 rounds of expansion. When CFSE- or VPD450-labeled autologous (auto) and non-autologous (non-auto) expanded Treg were infused into monkeys, the number of labeled auto-Treg in peripheral blood declined rapidly during the first week, but persisted at low levels in both normal and anti-thymocyte globulin plus rapamycin-treated (immunosuppressed; IS) animals for at least 3 weeks. By contrast, MHC-mismatched non-auto-Treg could not be detected in normal monkey blood or in blood of two out of the three IS monkeys by day 6 post-infusion. They were also more difficult to detect than auto-Treg in peripheral lymphoid tissue. Both auto- and non-auto-Treg maintained Ki67 expression early after infusion. Sequential monitoring revealed that adoptively-transferred auto-Treg maintained similarly high levels of Foxp3 and CD25 and low CD127 compared with endogenous Treg, although Foxp3 staining diminished over time in these non-transplanted recipients. Thus, infused ex vivo-expanded auto-Treg persist longer than MHC-mismatched non-auto-Treg in blood of non-human primates and can be detected in secondary lymphoid tissue. Host lymphodepletion and rapamycin administration did not consistently prolong the persistence of non-auto-Treg in these sites. PMID:25783759

Upper-Tropospheric Synoptic-Scale Waves. Part II: Maintenance and Excitation of Quasi Modes.

NASA Astrophysics Data System (ADS)

Rivest, Chantal; Farrell, Brian F.

1992-11-01

In a preceding paper a simple dynamical model for the maintenance of upper-tropospheric waves was proposed: the upper-level Eady normal modes. In this paper it is shown that these modes have counterparts in basic states with positive tropospheric gradients of potential vorticity, and that these counterparts can be maintained and excited on time scales consistent with observations.In the presence of infinitesimal positive tropospheric gradients of potential vorticity, the upper-level normal-mode solutions no longer exist. That the normal-mode solution disappears when gradients are infinitesimal represents an apparent singularity and challenges the interpretation of upper-level synoptic-scale waves as related to the upper-level Eady normal modes. What happens to the upper-level modal solution in the presence of tropospheric gradients of potential vorticity is examined in a series of initial-value experiments. Our results show that they become slowly decaying quasi modes. Mathematically the quasi modes consist of a superposition of singular modes sharply peaked in the phase speed domain, and their decay proceeds as the modes interfere with one another. We repeat these experiments in basic states with a smooth tropopause in the presence of tropospheric and stratospheric gradients, and similar results are obtained.Following a previous study by Farrell, a class of near-optimal initial conditions for the excitation of upper-level waves is identified. The initial conditions consist of upper-tropospheric disturbances that lean against the shear. They strongly excite upper-level waves not only in the absence of tropospheric potential vorticity gradients, but also in their presence. This result is important mathematically since it suggests that quasi modes are as likely to emerge from favorably configured initial disturbances as true normal modes, although the excitation is followed by a slow decay.

Biomechanical Analysis of Cervical Disc Replacement and Fusion Using Single Level, Two Level, and Hybrid Constructs.

PubMed

Gandhi, Anup A; Kode, Swathi; DeVries, Nicole A; Grosland, Nicole M; Smucker, Joseph D; Fredericks, Douglas C

2015-10-15

A biomechanical study comparing arthroplasty with fusion using human cadaveric C2-T1 spines. To compare the kinematics of the cervical spine after arthroplasty and fusion using single level, 2 level and hybrid constructs. Previous studies have shown that spinal levels adjacent to a fusion experience increased motion and higher stress which may lead to adjacent segment disc degeneration. Cervical arthroplasty achieves similar decompression but preserves the motion at the operated level, potentially decreasing the occurrence of adjacent segment disc degeneration. 11 specimens (C2-T1) were divided into 2 groups (BRYAN and PRESTIGE LP). The specimens were tested in the following order; intact, single level total disc replacement (TDR) at C5-C6, 2-level TDR at C5-C6-C7, fusion at C5-C6 and TDR at C6-C7 (Hybrid construct), and lastly a 2-level fusion. The intact specimens were tested up to a moment of 2.0 Nm. After each surgical intervention, the specimens were loaded until the primary motion (C2-T1) matched the motion of the respective intact state (hybrid control). An arthroplasty preserved motion at the implanted level and maintained normal motion at the nonoperative levels. Arthrodesis resulted in a significant decrease in motion at the fused level and an increase in motion at the unfused levels. In the hybrid construct, the TDR adjacent to fusion preserved motion at the arthroplasty level, thereby reducing the demand on the other levels. Cervical disc arthroplasty with both the BRYAN and PRESTIGE LP discs not only preserved the motion at the operated level, but also maintained the normal motion at the adjacent levels. Under simulated physiologic loading, the motion patterns of the spine with the BRYAN or PRESTIGE LP disc were very similar and were closer than fusion to the intact motion pattern. An adjacent segment disc replacement is biomechanically favorable to a fusion in the presence of a pre-existing fusion.

Patterns of Obesity and Lymph Fluid Level during the First Year of Breast Cancer Treatment: A Prospective Study

PubMed Central

Fu, Mei R.; Axelrod, Deborah; Guth, Amber A.; Fletcher, Jason; Qiu, Jeanna M.; Scagliola, Joan; Kleinman, Robin; Ryan, Caitlin E.; Chan, Nicholas; Haber, Judith

2015-01-01

Obesity is one of the risk factors for developing lymphedema following breast cancer treatment. We prospectively enrolled 140 women and followed the participants for 12 months after surgery to investigate patterns of obesity and lymph fluid level in the first year of cancer treatment. Electrical bioimpedance devices were used to measure weight, BMI, and percent of body fat as well as lymph fluid level. General instructions were given to the participants on maintaining pre-surgery weight. Among the 140 participants, 136 completed the study with 2.9% attrition. More than 60% of the participants were obese (30.8%) or overweight (32.4%), while only two participants were underweight and about 35% had normal weight. This pattern of obesity and overweight was consistent at 4–8 weeks and 12 months post-surgery. At 12 months post-surgery, the majority of the women (72.1%) maintained pre-surgery weight and 15.4% had >5% weight loss; 12.5% of the women increase >5% of their weight. Significantly more patients in the obesity group had lymphedema defined by L-Dex ratio >7.1 than those in the normal/underweight and overweight group at pre-surgery and 4–8 weeks post-surgery. There was a trend of more patients in the obesity group had L-Dex ratio >7.1 at 12 months post-surgery. Obesity and overweight remain among women at the time of cancer diagnosis and the patterns of obesity and overweight continue during the first year of treatment. General instructions on having nutrition-balanced and portion-appropriate diet and physical activities daily or weekly can be effective to maintain pre-surgery weight. PMID:26404383

WASP family proteins and formins compete in pseudopod- and bleb-based migration

PubMed Central

2018-01-01

Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration. PMID:29191847

The mechanism by which nonlinearity sustains turbulence in plane Couette flow

NASA Astrophysics Data System (ADS)

Nikolaidis, M.-A.; Farrell, B. F.; Ioannou, P. J.

2018-04-01

Turbulence in wall-bounded shear flow results from a synergistic interaction between linear non-normality and nonlinearity in which non-normal growth of a subset of perturbations configured to transfer energy from the externally forced component of the turbulent state to the perturbation component maintains the perturbation energy, while the subset of energy-transferring perturbations is replenished by nonlinearity. Although it is accepted that both linear non-normality mediated energy transfer from the forced component of the mean flow and nonlinear interactions among perturbations are required to maintain the turbulent state, the detailed physical mechanism by which these processes interact in maintaining turbulence has not been determined. In this work a statistical state dynamics based analysis is performed on turbulent Couette flow at R = 600 and a comparison to DNS is used to demonstrate that the perturbation component in Couette flow turbulence is replenished by a non-normality mediated parametric growth process in which the fluctuating streamwise mean flow has been adjusted to marginal Lyapunov stability. It is further shown that the alternative mechanism in which the subspace of non-normally growing perturbations is maintained directly by perturbation-perturbation nonlinearity does not contribute to maintaining the turbulent state. This work identifies parametric interaction between the fluctuating streamwise mean flow and the streamwise varying perturbations to be the mechanism of the nonlinear interaction maintaining the perturbation component of the turbulent state, and identifies the associated Lyapunov vectors with positive energetics as the structures of the perturbation subspace supporting the turbulence.

Magnesium and the Athlete.

PubMed

Volpe, Stella Lucia

2015-01-01

Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation in the body. It is a required mineral that is involved in more than 300 metabolic reactions in the body. Magnesium helps maintain normal nerve and muscle function, heart rhythm (cardiac excitability), vasomotor tone, blood pressure, immune system, bone integrity, and blood glucose levels and promotes calcium absorption. Because of magnesium's role in energy production and storage, normal muscle function, and maintenance of blood glucose levels, it has been studied as an ergogenic aid for athletes. This article will cover the general roles of magnesium, magnesium requirements, and assessment of magnesium status as well as the dietary intake of magnesium and its effects on exercise performance. The research articles cited were limited from those published in 2003 through 2014.

Differential functional magnetic resonance imaging response to food pictures in successful weight-loss maintainers relative to normal-weight and obese controls1234

PubMed Central

Haley, Andreana P; Sweet, Lawrence H; Phelan, Suzanne; Raynor, Hollie A; Del Parigi, Angelo; Cohen, Ron; Wing, Rena R

2009-01-01

Background: Prior research indicates that successful weight-loss maintainers (SWLs) work harder than people of normal weight to maintain their weight loss, including greater dietary restriction of fat and higher physical activity levels. However, little work to date has examined how SWLs differ biologically from normal-weight (NW) and obese controls. Objective: The objective was to compare the brain responses of SWLs to food pictures with those of NW and obese controls. Design: Blood oxygen level–dependent responses to high- and low-energy food pictures were measured in 18 NW controls, 16 obese controls, and 17 SWLs. Results: Group differences were identified in 4 regions, which indicated significant change in activation in response to the food pictures. SWLs showed greater activation in the left superior frontal region and right middle temporal region than did NW and obese controls—a pattern of results confirmed in exploratory voxel-wise analyses. Obese controls also showed greater activation in a bilateral precentral region. Conclusions: These results suggest that SWLs show greater activation in frontal regions and primary and secondary visual cortices—a pattern consistent with greater inhibitory control in response to food cues and greater visual attention to the food cues. A greater engagement of inhibitory control regions in response to food cues as well as a greater monitoring of foods may promote control of food intake and successful weight-loss maintenance. PMID:19675107

Impact of taurine depletion on glucose control and insulin secretion in mice.

PubMed

Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

2015-09-01

Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Redox environment in stem and differentiated cells: A quantitative approach.

PubMed

Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

2017-08-01

Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The effects of narrow and elevated path walking on aperture crossing.

PubMed

Hackney, Amy L; Cinelli, Michael E; Denomme, Luke T; Frank, James S

2015-06-01

The study investigated the impact that action capabilities have on identifying possibilities for action, particularly how postural threat influences the passability of apertures. To do this, the ability to maintain balance was challenged by manipulating the level of postural threat while walking. First, participants walked along a 7m path and passed through two vertical obstacles spaced 1.1-1.5×the shoulder width apart during normal walking. Next, postural threat was manipulated by having participants complete the task either walking on a narrow, ground level path or on an elevated/narrow path. Despite a decrease in walking speed as well as an increase in trunk sway in both the narrow and elevated/narrow walking conditions, the passability of apertures was only affected when the consequence of instability was greatest. In the elevated/narrow walking condition, individuals maintained a larger critical point (rotated their shoulders for larger aperture widths) compared to normal walking. However, this effect was not observed for the narrow path walking suggesting that the level of postural threat was not enough to impose similar changes to the critical point. Therefore, it appears that manipulating action capabilities by increasing postural threat does indeed influence aperture crossing behavior, however the consequence associated with instability must be high before both gait characteristics and the critical point are affected. Copyright © 2015 Elsevier B.V. All rights reserved.

Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

PubMed Central

Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie; Struck, Maggie; Ramirez, Harvey E.; Jordan, Juan; Andrutis, Karl; Chou, Janice Y.; Byrne, Barry J.

2010-01-01

Abstract Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-α. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver. PMID:20163245

Quercetin Attenuates Cell Survival, Inflammation, and Angiogenesis via Modulation of AKT Signaling in Murine T-Cell Lymphoma.

PubMed

Maurya, Akhilendra Kumar; Vinayak, Manjula

2017-04-01

AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice. Protein level was determined by Western blotting. Nitric oxide (NO) level was estimated spectrophotometrically using Griess reagent. Results show downregulation in phosphorylation of AKT and PDK1 by quercetin, which was consistent with decreased phosphorylation of downstream survival factors such as BAD, GSK-3β, mTOR, and IkBα. Further, quercetin attenuated the levels of angiogenic factor VEGF-A and inflammatory enzymes COX-2 and iNOS as well as NO levels, whereas it increased the levels of phosphatase PTEN. Overall results suggest that quercetin modulates AKT signaling leading to attenuation of cell survival, inflammation, and angiogenesis in lymphoma-bearing mice.

Levels-of-Processing Effect on Frontotemporal Function in Schizophrenia During Word Encoding and Recognition

PubMed Central

Ragland, J. Daniel; Gur, Ruben C.; Valdez, Jeffrey N.; Loughead, James; Elliott, Mark; Kohler, Christian; Kanes, Stephen; Siegel, Steven J.; Moelter, Stephen T.; Gur, Raquel E.

2015-01-01

Objective Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. Method Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. Results Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. Conclusions Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies. PMID:16199830

Evaluation of Normalization Methods on GeLC-MS/MS Label-Free Spectral Counting Data to Correct for Variation during Proteomic Workflows

NASA Astrophysics Data System (ADS)

Gokce, Emine; Shuford, Christopher M.; Franck, William L.; Dean, Ralph A.; Muddiman, David C.

2011-12-01

Normalization of spectral counts (SpCs) in label-free shotgun proteomic approaches is important to achieve reliable relative quantification. Three different SpC normalization methods, total spectral count (TSpC) normalization, normalized spectral abundance factor (NSAF) normalization, and normalization to selected proteins (NSP) were evaluated based on their ability to correct for day-to-day variation between gel-based sample preparation and chromatographic performance. Three spectral counting data sets obtained from the same biological conidia sample of the rice blast fungus Magnaporthe oryzae were analyzed by 1D gel and liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Equine myoglobin and chicken ovalbumin were spiked into the protein extracts prior to 1D-SDS- PAGE as internal protein standards for NSP. The correlation between SpCs of the same proteins across the different data sets was investigated. We report that TSpC normalization and NSAF normalization yielded almost ideal slopes of unity for normalized SpC versus average normalized SpC plots, while NSP did not afford effective corrections of the unnormalized data. Furthermore, when utilizing TSpC normalization prior to relative protein quantification, t-testing and fold-change revealed the cutoff limits for determining real biological change to be a function of the absolute number of SpCs. For instance, we observed the variance decreased as the number of SpCs increased, which resulted in a higher propensity for detecting statistically significant, yet artificial, change for highly abundant proteins. Thus, we suggest applying higher confidence level and lower fold-change cutoffs for proteins with higher SpCs, rather than using a single criterion for the entire data set. By choosing appropriate cutoff values to maintain a constant false positive rate across different protein levels (i.e., SpC levels), it is expected this will reduce the overall false negative rate, particularly for proteins with higher SpCs.

The ability of multipotent mesenchymal stromal cells from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells.

PubMed

Sorokina, Tamara; Shipounova, Irina; Bigildeev, Alexey; Petinati, Nataliya; Drize, Nina; Turkina, Anna; Chelysheva, Ekaterina; Shukhov, Oleg; Kuzmina, Larisa; Parovichnikova, Elena; Savchenko, Valery

2016-09-01

The development of leukemia impairs normal hematopoiesis and marrow stromal microenvironment. The aim of the investigation was to study the ability of multipotent mesenchymal stromal cells (MSCs) derived from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells. MSCs were obtained from the bone marrow of 14 patients with acute lymphoblastic (ALL), 25 with myeloid (AML), and 15 with chronic myeloid (CML) leukemia. As a control, MSCs from 22 healthy donors were used. The incidence of cobblestone area forming cells (CAFC 7-8 d) in the bone marrow of healthy donor cultivated on the supportive layer of patients MSCs was measured. The ability of MSCs from AML and ALL patients at the moment of diagnosis to maintain normal CAFC was significantly decreased when compared to donors. After chemotherapy, the restoration of ALL patients' MSCs functions was slower than that of AML. CML MSCs maintained CAFC better than donors' at the moment of diagnosis and this ability increased with treatment. The ability of patients' MSCs to maintain normal hematopoietic progenitor cells was shown to change in comparison with MSCs from healthy donors and depended on nosology. During treatment, the functional capacity of patients' MSCs had been partially restored. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term Safety of Dichloroacetate in Congenital Lactic Acidosis

PubMed Central

Abdelmalak, Monica; Lew, Alicia; Ramezani, Ryan; Shroads, Albert L.; Coats, Bonnie S.; Langaee, Taimour; Shankar, Meena N.; Neiberger, Richard E.; Subramony, S.H.; Stacpoole, Peter W.

2013-01-01

We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the E1α subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (1 patient), IV (3 patients) or I+IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 hours) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean ± SD: 23.5 ± 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets. PMID:23611579

Self-teaching digital-computer program for fail-operational control of a turbojet engine in a sea-level test stand

NASA Technical Reports Server (NTRS)

Wallhagen, R. E.; Arpasi, D. J.

1974-01-01

The design and evaluation are described of a digital turbojet engine control which is capable of sensing catastrophic failures in either the engine rotor speed or the compressor discharge static-pressure signal and is capable of switching control modes to maintain near normal operation. The control program was developed for and tested on a turbojet engine located in a sea-level test stand. The control program is also capable of acquiring all the data that are necessary for the fail-operational control to function.

Pseudohypoparathyroidism: a rare but important cause of hypocalcaemia

PubMed Central

Chong, Pui Lin; Meeking, Darryl R

2013-01-01

We present a 46-year-old Caucasian lady with symptomatic hypocalcaemia. Investigations revealed markedly raised parathyroid hormone (PTH) levels with vitamin D deficiency. A number of conditions causing secondary hyperparathyroidism were ruled out from her medical history and initial investigations. The main differential diagnoses were vitamin D deficiency and PTH resistance (pseudohypoparathyroidism, PHP). With high-normal serum phosphate and normal alkaline phosphatase, and a lack of symptoms associated with osteomalacia, vitamin D deficiency alone was unlikely to be the cause of hypocalcaemia. Given a normal physical appearance, genetic testing was arranged and confirmed the diagnosis of PHP type Ib. She is currently taking activated vitamin D to maintain calcium homeostasis. PTH resistance is the hallmark of PHP, a rare complex genetic disorder, which can be easily missed resulting in potentially serious consequences. PMID:23345494

Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

PubMed Central

2010-01-01

Background Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women. Methods A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry. Results Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer. Conclusion Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy. PMID:21162745

DUOX enzyme activity promotes AKT signalling in prostate cancer cells.

PubMed

Pettigrew, Christopher A; Clerkin, John S; Cotter, Thomas G

2012-12-01

Reactive oxygen species (ROS) and oxidative stress are related to tumour progression, and high levels of ROS have been observed in prostate tumours compared to normal prostate. ROS can positively influence AKT signalling and thereby promote cell survival. The aim of this project was to establish whether the ROS generated in prostate cancer cells positively regulate AKT signalling and enable resistance to apoptotic stimuli. In PC3 cells, dual oxidase (DUOX) enzymes actively generate ROS, which inactivate phosphatases, thereby maintaining AKT phosphorylation. Inhibition of DUOX by diphenylene iodium (DPI), intracellular calcium chelation and small-interfering RNA (siRNA) resulted in lower ROS levels, lower AKT and glycogen synthase kinase 3β (GSK3β) phosphorylation, as well as reduced cell viability and increased susceptibility to apoptosis stimulating fragment (FAS) induced apoptosis. This report shows that ROS levels in PC3 cells are constitutively maintained by DUOX enzymes, and these ROS positively regulate AKT signalling through inactivating phosphatases, leading to increased resistance to apoptosis.

Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds123

PubMed Central

Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun

2015-01-01

Abstract Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood. PMID:26730405

Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds.

PubMed

Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun; Krimm, Robin F

2015-01-01

Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood.

Exclusion of particulate allergens by window air conditioners.

PubMed

Solomon, W R; Burge, H A; Boise, J R

1980-04-01

Effects of window air-conditioner operation on intramural particle levels were assessed in the bedrooms of 20 homes and in 10 outpatient clinic examining rooms during late summer periods. At each site, pollen and spore collections in the mechanically cooled room and a normally ventilated counterpart were compared using volumetric impactors. Substantially lower particle recoveries (median = 16/m3) were found in air-conditioned rooms than in those with open windows alone (median = 253 particles/m3). Furthermore, substantial exclusion of small (e.g., Ganoderma spores) as well as large (ragweed pollens) aerosol components were found by window units. Control studies within normally ventilated rooms and outside their open windows showed a marked but variable inward flux of particles. Window units appear to substantially reduce indoor allergan levels by maintaining the isolation of enclosed spaces from particle-bearing outdoor air.

A case of classical maple syrup urine disease that was successfully managed by living donor liver transplantation.

PubMed

Takano, Chika; Ishige, Mika; Ogawa, Erika; Usui, Hiromi; Kagawa, Reiko; Tajima, Go; Fujiki, Ryoji; Fukao, Toshiyuki; Mizuta, Koichi; Fuchigami, Tatsuo; Takahashi, Shori

2017-08-01

Classical MSUD is often fatal without appropriate medical interventions because of metabolic crisis. There are numerous reports suggesting the therapeutic potential of deceased donor liver transplantation for MSUD. However, the usefulness of LDLT for MSUD is unknown. We report a case of classical MSUD, which was successfully managed by LDLT from the patient's father at 1 year of age. Abnormal brain findings, which were cured with effective treatment, gradually disappeared after LDLT. The patient then developed normally. Findings from this case suggest the importance of LDLT for maintaining low leucine levels and subsequent normal neurological development. Although LDLT involves a modest surgical insult, LDLT with a related donor achieves acceptable leucine levels for life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Southeast Asia Report.

DTIC Science & Technology

1987-05-27

with Aspertame (which is 180 times sweeter than sucrose), Acesulfam-K (which is a non-calorific intensely sweet organic salt) and high fructose corn ...The Defence Signals Directorate’s earlier antennas for intercepting and locating normal high -frequency transmissions have been improved at major...thrust of De- fence Minister Kim Beazley’s white pa- per. Australia has to be self-reliant. It has to maintain a high level of intelli- gence

Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease.

PubMed

Kanai, Takahiro; Ito, Takane; Odaka, Jun; Saito, Takashi; Aoyagi, Jun; Betsui, Hiroyuki; Yamagata, Takanori

2016-03-01

Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear. The worldwide shortage of agalsidase-β in 2009 forced dose reduction of administration. It showed that the proteinuria emerged like surges, followed by temporary plasma GL-3 elevations in the early stages of classic Fabry disease. Additionally, it also showed that 1 mg/kg of agalsidase-β every other week could clear the GL-3 accumulations from podocytes and was required to maintain negative proteinuria and normal plasma GL-3 levels. This observation of a young patient with classic Fabry disease about 5 years reveals that the long-term, low-dose agalsidase-β caused proteinuria surges, but not persistent proteinuria, followed by temporary plasma GL-3 elevations, and agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes and was required to maintain normal urinalysis and plasma GL-3 levels.

Somatic proembryo production from excised, wounded zygotic carrot embryos on hormone-free medium: evaluation of the effects of pH, ethylene and activated charcoal

NASA Technical Reports Server (NTRS)

Smith, D. L.; Krikorian, A. D.

1990-01-01

Wounded zygotic embryos of cultivated carrot produce somatic proembryos on hormone-free nutrient medium containing 1 mM NH4+ as the sole nitrogen source. Continued maintenance of proembryos on this medium leads to a "pure" culture of preglobular stage proembryos (PGSPs). Ethylene had no effect on this process. Also, somatic embryo production was not affected by growing cultures on activated charcoal-impregnated filter papers. However, somatic proembyros initiated on activated charcoal papers were not maintainable as PGSPs and developed into later embryo stages. Normally, medium pH dropped from 5.7 to 4 during each subculture period, but when using activated charcoal papers the pH endpoint was around 6 - 7 due to a leachable substance(s) within the filter papers. When powdered, activated charcoal was used in the medium as an adsorbent of products potentially released after wounding, pH dropped at the normal rate and to the expected levels; proembryos did not mature into later embryo stages and were maintainable exclusively as PGSPs. Low pH (approximately 4) is detrimental to proembyro production, but is essential to maintaining PGSPs on hormone-free nutrient medium, whereas a sustained pH > or = 5.7 allows continued development of PGSPs into later embryo stages.

Role of 11beta-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure.

PubMed

Yeyati, N L; Altuna, M E; Damasco, M C; Mac Laughlin, M A

2010-01-01

Aldosterone concentrations vary in advanced chronic renal failure (CRF). The isozyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), which confers aldosterone specificity for mineralocorticoid receptors in distal tubules and collecting ducts, has been reported to be decreased or normal in patients with renal diseases. Our objective was to determine the role of aldosterone and 11beta-HSD2 renal microsome activity, normalized for glomerular filtration rate (GFR), in maintaining K+ homeostasis in 5/6 nephrectomized rats. Male Wistar rats weighing 180-220 g at the beginning of the study were used. Rats with experimental CRF obtained by 5/6 nephrectomy (N = 9) and sham rats (N = 10) were maintained for 4 months. Systolic blood pressure and plasma creatinine (Pcr) concentration were measured at the end of the experiment. Sodium and potassium excretion and GFR were evaluated before and after spironolactone administration (10 mg.kg-1.day-1 for 7 days) and 11beta-HSD2 activity on renal microsomes was determined. Systolic blood pressure (means +/- SEM; Sham = 105 +/- 8 and CRF = 149 +/- 10 mmHg) and Pcr (Sham = 0.42 +/- 0.03 and CRF = 2.53 +/- 0.26 mg/dL) were higher (P < 0.05) while GFR (Sham = 1.46 +/- 0.26 and CRF = 0.61 +/- 0.06 mL/min) was lower (P < 0.05) in CRF, and plasma aldosterone (Pald) was the same in the two groups. Urinary sodium and potassium excretion was similar in the two groups under basal conditions but, after spironolactone treatment, only potassium excretion was decreased in CRF rats (sham = 0.95 +/- 0.090 (before) vs 0.89 +/- 0.09 microEq/min (after) and CRF = 1.05 +/- 0.05 (before) vs 0.37 +/- 0.07 microEq/min (after); P < 0.05). 11beta-HSD2 activity on renal microsomes was lower in CRF rats (sham = 0.807 +/- 0.09 and CRF = 0.217 +/- 0.07 nmol.min-1.mg protein-1; P < 0.05), although when normalized for mL GFR it was similar in both groups. We conclude that K+ homeostasis is maintained during CRF development despite normal Pald levels. This adaptation may be mediated by renal 11beta-HSD2 activity, which, when normalized for GFR, became similar to that of control rats, suggesting that mineralocorticoid receptors maintain their aldosterone selectivity.

Effects of Mesalamine Treatment on Gut Barrier Integrity Following Burn Injury

PubMed Central

Cannon, Abigail R.; Akhtar, Suhail; Hammer, Adam M.; Morris, Niya L.; Javorski, Mike J.; Li, Xiaoling; Kennedy, Richard H.; Gamelli, Richard L.; Choudhry, Mashkoor A.

2016-01-01

Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, we examined whether therapeutic intervention with mesalamine (5-ASA), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an ~20% total body surface area dorsal scald burn and resuscitated with either 1mL normal saline or 100mg/kg of 5-ASA dissolved in saline. We examined intestinal transit and permeability along with levels of small intestine epithelial cell pro-inflammatory cytokines and tight junction protein expression one day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed one day after burn injury, which accompanied a significant increase in gut permeability. We found a substantial increase in the levels of IL-6 (by ~1.5 fold) and IL-18 (by ~2.5 fold) in small intestine epithelial cells one day after injury. Furthermore, burn injury decreases expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn induced increase in permeability, partially restored normal intestinal transit, normalized levels of the pro-inflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin to that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury. PMID:27388883

Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury.

PubMed

Cannon, Abigail R; Akhtar, Suhail; Hammer, Adam M; Morris, Niya L; Javorski, Michael J; Li, Xiaoling; Kennedy, Richard H; Gamelli, Richard L; Choudhry, Mashkoor A

2016-01-01

Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, the authors examined whether therapeutic intervention with mesalamine (5-aminosalicylic acid [5-ASA]), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an approximately 20% TBSA dorsal scald burn and resuscitated with either 1 ml normal saline or 100 mg/kg of 5-ASA dissolved in saline. The authors examined intestinal transit and permeability along with the levels of small intestine epithelial cell proinflammatory cytokines and tight junction protein expression 1 day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed 1 day after burn injury, which accompanied a significant increase in gut permeability. The authors found a substantial increase in the levels of interleukin (IL)-6 (by ~1.5-fold) and IL-18 (by ~2.5-fold) in the small intestine epithelial cells 1 day after injury. Furthermore, burn injury decreases the expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn-induced increase in permeability, partially restored normal intestinal transit, normalized the levels of the proinflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin compared with that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury.

Nicotinamide extends replicative lifespan of human cells.

PubMed

Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

2006-10-01

We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

Modulation of Wolframin Expression in Human Placenta during Pregnancy: Comparison among Physiological and Pathological States

PubMed Central

Perna, Angelica; Iannaccone, Alessandro; Cobellis, Luigi; De Luca, Antonio

2014-01-01

The WFS1 gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of the WFS1 gene in mice causes progressive β-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ. PMID:24588001

Vitamin D: the light side of sunshine.

PubMed

Mason, R S; Sequeira, V B; Gordon-Thomson, C

2011-09-01

Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.

Dysmegakaryocytopoiesis and maintaining platelet count in patients with plasma cell neoplasm.

PubMed

Mair, Yasmin; Zheng, Yan; Cai, Donghong

2013-05-01

Dysmegakaryocytopoiesis in patients with the plasma cell neoplasm (PCN) is rarely discussed in the literature. The puzzling phenomenon, which PCN patients maintaining normal platelet count even when the marrow is mostly replaced by plasma cells, is hardly explored. This study was aimed to determine the frequency of dysmegakaryocytopoiesis in PCN and the relationships between bone marrow (BM) plasma cell percentage, plasma cell immunomarkers, the severity of dysmegakaryocytopoiesis, and peripheral blood platelet count in PCN. We randomly selected 16 cases of PCN, among which 4 were with monoclonal gammopathy of undetermined significance and 12 were with plasma cell myeloma. OUR STUDY SHOWED THAT: (1) Dysmegakaryocytopoiesis was present in all the selected cases of PCN and its severity was not correlated with the percentage of the plasma cells in BM; (2) almost all patients maintained normal platelet count even when BM was mostly replaced by plasma cells; (3) immunomarkers of the neoplastic plasma cells were not associated with dysmegakaryocytopoiesis or maintaining of platelet count. The possible mechanisms behind dysmegakaryocytopoiesis and maintaining of platelet count were also discussed. Despite the universal presence of dysmegakaryocytopoiesis in PCN, the platelet count is maintained at normal range.

A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

PubMed Central

Gerard-O'Riley, Rita L.; Acton, Dena; McQueen, Amie K.; Strobel, Isabel E.; Witcher, Phillip C.; Feng, Jian Q.; Econs, Michael J.

2017-01-01

Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. PMID:28005411

A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice.

PubMed

Ichikawa, Shoji; Gerard-O'Riley, Rita L; Acton, Dena; McQueen, Amie K; Strobel, Isabel E; Witcher, Phillip C; Feng, Jian Q; Econs, Michael J

2017-03-01

Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. Copyright © 2017 by the Endocrine Society.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

PubMed

Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain.

PubMed

Currie, Ko W; Molinaro, Alyssa M; Pearson, Bret J

2016-11-19

The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, Smed-nkx2.1 and Smed-arx , which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian hedgehog ligand ( Smed-hh ), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core hh signal transduction genes, and consistent hh signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian hh signaling molecule in the adult CNS.

Assessment of Alternative RF Linac Structures for APT

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

The APT program has been examining both normal and superconducting variants of the APT linac for the past two years. A decision on which of the two will be the selected technology will depend upon several considerations including the results of ongoing feasibility experiments, the performance and overall attractiveness of each of the design concepts, and an assessment of the system-level features of both alternatives. The primary objective of the Assessment of Alternative RF Linac Structures for APT study reported herein was to assess and compare, at the system-level, the performance, capital and life cycle costs, reliability/availability/maintainability (RAM) and manufacturingmore » schedules of APT RF linear accelerators based upon both superconducting and normal conducting technologies. A secondary objective was to perform trade studies to explore opportunities for system optimization, technology substitution and alternative growth pathways and to identify sensitivities to design uncertainties.« less

Boiling water neutronic reactor incorporating a process inherent safety design

DOEpatents

Forsberg, C.W.

1985-02-19

A boiling-water reactor core is positioned within a prestressed concrete reactor vessel of a size which will hold a supply of coolant water sufficient to submerge and cool the reactor core by boiling for a period of at least one week after shutdown. Separate volumes of hot, clean (nonborated) water for cooling during normal operation and cool highly borated water for emergency cooling and reactor shutdown are separated by an insulated wall during normal reactor operation with contact between the two water volumes being maintained at interfaces near the top and bottom ends of the reactor vessel. Means are provided for balancing the pressure of the two water volumes at the lower interface zone during normal operation to prevent entry of the cool borated water into the reactor core region, for detecting the onset of excessive power to coolant flow conditions in the reactor core and for detecting low water levels of reactor coolant. Cool borated water is permitted to flow into the reactor core when low reactor coolant levels or excessive power to coolant flow conditions are encountered.

Boiling water neutronic reactor incorporating a process inherent safety design

DOEpatents

Forsberg, Charles W.

1987-01-01

A boiling-water reactor core is positioned within a prestressed concrete reactor vessel of a size which will hold a supply of coolant water sufficient to submerge and cool the reactor core by boiling for a period of at least one week after shutdown. Separate volumes of hot, clean (non-borated) water for cooling during normal operation and cool highly borated water for emergency cooling and reactor shutdown are separated by an insulated wall during normal reactor operation with contact between the two water volumes being maintained at interfaces near the top and bottom ends of the reactor vessel. Means are provided for balancing the pressure of the two volumes at the lower interface zone during normal operation to prevent entry of the cool borated water into the reactor core region, for detecting the onset of excessive power to coolant flow conditions in the reactor core and for detecting low water levels of reactor coolant. Cool borated water is permitted to flow into the reactor core when low reactor coolant levels or excessive power to coolant flow conditions are encountered.

Oxcarbazepine Therapy for Complete Central Diabetes Insipidus.

PubMed

Abdallah, Basmah; Hodgins, Spencer; Landry, Daniel; O'shea, Michael; Braden, Gregory

2018-01-01

Oxcarbazepine and carbamazepine cause hyponatremia by unknown mechanisms. We describe a patient with complete central diabetes insipidus and seizures who developed worsening hyponatremia when her dose of oxcarbazepine was increased. The patient maintained a normal serum sodium level and has had appropriately concentrated urine for 5 years on just oxcarbazepine, despite undetectable antidiuretic hormone (ADH) levels. This suggests that oxcarbazepine (or one of its metabolites) may stimulate collecting tubule V2 receptor-G protein complex independent of ADH, resulting in increased renal tubular water reabsorption. Oxcarbazepine may be useful as an alternative therapy for patients with central diabetes insipidus.

Does elevated pCO2 affect reef octocorals?

PubMed

Gabay, Yasmin; Benayahu, Yehuda; Fine, Maoz

2013-03-01

Increasing anthropogenic pCO2 alters seawater chemistry, with potentially severe consequences for coral reef growth and health. Octocorals are the second most important faunistic component in many reefs, often occupying 50% or more of the available substrate. Three species of octocorals from two families were studied in Eilat (Gulf of Aqaba), comprising the zooxanthellate Ovabunda macrospiculata and Heteroxenia fuscescens (family Xeniidae), and Sarcophyton sp. (family Alcyoniidae). They were maintained under normal (8.2) and reduced (7.6 and 7.3) pH conditions for up to 5 months. Their biolological features, including protein concentration, polyp weight, density of zooxanthellae, and their chlorophyll concentration per cell, as well as polyp pulsation rate, were examined under conditions more acidic than normal, in order to test the hypothesis that rising pCO2 would affect octocorals. The results indicate no statistically significant difference between the octocorals exposed to reduced pH values compared to the control. It is therefore suggested that the octocorals' tissue may act as a protective barrier against adverse pH conditions, thus maintaining them unharmed at high levels of pCO2.

High activity of mitochondrial glycerophosphate dehydrogenase and glycerophosphate-dependent ROS production in prostate cancer cell lines.

PubMed

Chowdhury, Subir K R; Gemin, Adam; Singh, Gurmit

2005-08-12

Most malignant cells are highly glycolytic and produce high levels of reactive oxygen species (ROS) compared to normal cells. Mitochondrial glycerophosphate dehydrogenase (mGPDH) participates in the reoxidation of cytosolic NADH by delivering reducing equivalents from this molecule into the electron transport chain, thus sustaining glycolysis. Here, we investigate the role of mGPDH in maintaining an increased rate of glycolysis and evaluate glycerophosphate-dependent ROS production in prostate cancer cell lines (LNCaP, DU145, PC3, and CL1). Immunoblot, polarographic, and spectrophotometric analyses revealed that mGPDH abundance and activity was significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A. Furthermore, both the glycolytic capacity and glycerophosphate-dependent ROS production was increased 1.68- to 4.44-fold and 5- to 7-fold, respectively, in prostate cancer cell lines when compared to PNT1A cells. Overall, these data demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to ROS production in prostate cancer cells.

Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.

PubMed

Saunders, Christopher T; Wong, Wendy S W; Swamy, Sajani; Becq, Jennifer; Murray, Lisa J; Cheetham, R Keira

2012-07-15

Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity. We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. We demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests. The Strelka workflow source code is available at ftp://strelka@ftp.illumina.com/. csaunders@illumina.com

Resource Optimization Techniques and Security Levels for Wireless Sensor Networks Based on the ARSy Framework.

PubMed

Parenreng, Jumadi Mabe; Kitagawa, Akio

2018-05-17

Wireless Sensor Networks (WSNs) with limited battery, central processing units (CPUs), and memory resources are a widely implemented technology for early warning detection systems. The main advantage of WSNs is their ability to be deployed in areas that are difficult to access by humans. In such areas, regular maintenance may be impossible; therefore, WSN devices must utilize their limited resources to operate for as long as possible, but longer operations require maintenance. One method of maintenance is to apply a resource adaptation policy when a system reaches a critical threshold. This study discusses the application of a security level adaptation model, such as an ARSy Framework, for using resources more efficiently. A single node comprising a Raspberry Pi 3 Model B and a DS18B20 temperature sensor were tested in a laboratory under normal and stressful conditions. The result shows that under normal conditions, the system operates approximately three times longer than under stressful conditions. Maintaining the stability of the resources also enables the security level of a network's data output to stay at a high or medium level.

Resource Optimization Techniques and Security Levels for Wireless Sensor Networks Based on the ARSy Framework

PubMed Central

Kitagawa, Akio

2018-01-01

Wireless Sensor Networks (WSNs) with limited battery, central processing units (CPUs), and memory resources are a widely implemented technology for early warning detection systems. The main advantage of WSNs is their ability to be deployed in areas that are difficult to access by humans. In such areas, regular maintenance may be impossible; therefore, WSN devices must utilize their limited resources to operate for as long as possible, but longer operations require maintenance. One method of maintenance is to apply a resource adaptation policy when a system reaches a critical threshold. This study discusses the application of a security level adaptation model, such as an ARSy Framework, for using resources more efficiently. A single node comprising a Raspberry Pi 3 Model B and a DS18B20 temperature sensor were tested in a laboratory under normal and stressful conditions. The result shows that under normal conditions, the system operates approximately three times longer than under stressful conditions. Maintaining the stability of the resources also enables the security level of a network’s data output to stay at a high or medium level. PMID:29772773

Nutritional management of replacement sheep utilizing southern forages: a review.

PubMed

Chappell, G L

1993-11-01

Intensive sheep production systems seem to be an appropriate means of fully using the available resources, particularly the forages, of the southern region. In such systems, ewes should lamb first at approximately 1 yr of age. Programs to accomplish this goal must be well-planned and carefully integrated and executed. The primary goal is to achieve two-thirds of the ewe's projected mature weight before exposure for breeding. General management must reduce heat stress and parasitism. Forage quality must be maintained at a level consistent with National Research Council requirements for energy and protein. Protein is not normally a limiting factor. Energy supplementation and grazing pressure can be used to maintain growth without over-condition, which reduces subsequent performance.

Multi-scale modeling of APC and [Formula: see text]-catenin regulation in the human colonic crypt.

PubMed

Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

2018-06-01

Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas. We formulate a PDE model describing cell movement and reproduction in a static crypt domain. We consider a single cell population whose proliferative capabilities are determined by stemness, a quantity defined by intracellular levels of adenomatous polyposis coli (APC) scaffold protein and [Formula: see text]-catenin. We fit APC regulation parameters to biological data that describe normal protein gradients in the crypt. We also fit cell movement and protein flux parameters to normal crypt characteristics such as renewal time, total cell count, and proportion of proliferating cells. The model is used to investigate abnormal crypt dynamics when subjected to a diminished APC gradient, a scenario synonymous to mutations in the APC gene. We find that a 25% decrease in APC synthesis leads to a fraction of 0.88 proliferative, which is reflective of normal-appearing FAP crypts. A 50% drop in APC activity yields a fully proliferative crypt showing a doubling of the level of stemness, which characterizes the initial stages of colorectal cancer development. A sensitivity analysis of APC regulation parameters shows the perturbation of factors that is required to restore crypt dynamics to normal in the case of APC mutations.

Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent anti-tumor activity

PubMed Central

Caruso, Hillary G.; Hurton, Lenka V.; Najjar, Amer; Rushworth, David; Ang, Sonny; Olivares, Simon; Mi, Tiejuan; Switzer, Kirsten; Singh, Harjeet; Huls, Helen; Lee, Dean A.; Heimberger, Amy B.; Champlin, Richard E.; Cooper, Laurence J. N.

2015-01-01

Many tumors over express tumor-associated antigens relative to normal tissue, such as epidermal growth factor receptor (EGFR). This limits targeting by human T cells modified to express chimeric antigen receptors (CARs) due to potential for deleterious recognition of normal cells. We sought to generate CAR+ T cells capable of distinguishing malignant from normal cells based on the disparate density of EGFR expression by generating two CARs from monoclonal antibodies which differ in affinity. T cells with low affinity Nimo-CAR selectively targeted cells over-expressing EGFR, but exhibited diminished effector function as the density of EGFR decreased. In contrast, the activation of T cells bearing high affinity Cetux-CAR was not impacted by the density of EGFR. In summary, we describe the generation of CARs able to tune T-cell activity to the level of EGFR expression in which a CAR with reduced affinity enabled T cells to distinguish malignant from non-malignant cells. PMID:26330164

TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

PubMed

Ghosh, Abhishek; Rideout, Elizabeth J; Grewal, Savraj S

2014-10-01

The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs) from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

TIF-IA-Dependent Regulation of Ribosome Synthesis in Drosophila Muscle Is Required to Maintain Systemic Insulin Signaling and Larval Growth

PubMed Central

Ghosh, Abhishek; Rideout, Elizabeth J.; Grewal, Savraj S.

2014-01-01

The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis—a limiting step in ribosome biogenesis—via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs) from the brain and increased expression of Imp-L2—a secreted factor that binds and inhibits dILP activity—from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis. PMID:25356674

Aquaporin-0 Targets Interlocking Domains to Control the Integrity and Transparency of the Eye Lens

PubMed Central

Lo, Woo-Kuen; Biswas, Sondip K.; Brako, Lawrence; Shiels, Alan; Gu, Sumin; Jiang, Jean X.

2014-01-01

Purpose. Lens fiber cell membranes contain aquaporin-0 (AQP0), which constitutes approximately 50% of the total fiber cell membrane proteins and has a dual function as a water channel protein and an adhesion molecule. Fiber cell membranes also develop an elaborate interlocking system that is required for maintaining structural order, stability, and lens transparency. Herein, we used an AQP0-deficient mouse model to investigate an unconventional adhesion role of AQP0 in maintaining a normal structure of lens interlocking protrusions. Methods. The loss of AQP0 in AQP0−/− lens fibers was verified by Western blot and immunofluorescence analyses. Changes in membrane surface structures of wild-type and AQP0−/− lenses at age 3 to 12 weeks were examined with scanning electron microscopy. Preferential distribution of AQP0 in wild-type fiber cell membranes was analyzed with immunofluorescence and immunogold labeling using freeze-fracturing transmission electron microscopy. Results. Interlocking protrusions in young differentiating fiber cells developed normally but showed minor abnormalities at approximately 50 μm deep in the absence of AQP0 in all ages studied. Strikingly, protrusions in maturing fiber cells specifically underwent uncontrolled elongation, deformation, and fragmentation, while cells still retained their overall shape. Later in the process, these changes eventually resulted in fiber cell separation, breakdown, and cataract formation in the lens core. Immunolabeling at the light microscopy and transmission electron microscopy levels demonstrated that AQP0 was particularly enriched in interlocking protrusions in wild-type lenses. Conclusions. This study suggests that AQP0 exerts its primary adhesion or suppression role specifically to maintain the normal structure of interlocking protrusions that is critical to the integrity and transparency of the lens. PMID:24458158

Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine.

PubMed

Zhang, Lihua; Cheng, Huilin; Shi, Jixin; Chen, Jun

2007-02-01

The protective effect against ischemic stroke by systemic hypothermia is limited by the cooling rate and it has severe complications. This study was designed to evaluate the effect of SBH induced by epidural cooling on infarction volume in a swine model of PMCAO. Permanent middle cerebral artery occlusion was performed in 12 domestic swine assigned to groups A and B. In group A, the cranial and rectal temperatures were maintained at normal range (37 degrees C-39 degrees C) for 6 hours after PMCAO. In group B, cranial temperature was reduced to moderate (deep brain, <30 degrees C) and deep (brain surface, <20 degrees C) temperature and maintained at that level for 5 hours after 1 hour after PMCAO, by the epidural cooling method. All animals were euthanized 6 hours after MCAO; their brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride and their infarct volumes were calculated. The moderate and deep brain temperature (at deep brain and brain surface) can be induced by rapid epidural cooling, whereas the rectal temperature was maintained within normal range. The infarction volume after PMCAO was significantly reduced by epidural cooling compared with controls (13.73% +/- 1.82% vs 5.62% +/- 2.57%, P < .05). The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.

Finger blood content, light transmission, and pulse oximetry errors.

PubMed

Craft, T M; Lawson, R A; Young, J D

1992-01-01

The changes in light emitting diode current necessary to maintain a constant level of light incident upon a photodetector were measured in 20 volunteers at the two wavelengths employed by pulse oximeters. Three states of finger blood content were assessed; exsanguinated, hyperaemic, and normal. The changes in light emitting diode current with changes in finger blood content were small and are not thought to represent a significant source of error in saturation as measured by pulse oximetry.

Method and apparatus for rapid thrust increases in a turbofan engine

NASA Technical Reports Server (NTRS)

Cornett, J. E.; Corley, R. C.; Fraley, T. O.; Saunders, A. A., Jr. (Inventor)

1980-01-01

Upon a landing approach, the normal compressor stator schedule of a fan speed controlled turbofan engine is temporarily varied to substantially close the stators to thereby increase the fuel flow and compressor speed in order to maintain fan speed and thrust. This running of the compressor at an off-design speed substantially reduces the time required to subsequently advance the engine speed to the takeoff thrust level by advancing the throttle and opening the compressor stators.

CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors

PubMed Central

Negrotto, Soledad; Ng, Kwok Peng; Jankowska, Ania M.; Bodo, Juraj; Gopalan, Banu; Guinta, Kathryn; Mulloy, James C.; Hsi, Eric; Maciejewski, Jaroslaw; Saunthararajah, Yogen

2011-01-01

The DNA hypomethylating drug decitabine maintains normal hematopoietic stem cell (HSC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. The basis for these contrasting cell-fates, and for selective CpG hypomethylation by decitabine, is poorly understood. Promoter CpGs, with methylation measured by microarray, were classified by the direction of methylation change with normal myeloid maturation. In AML cells, the methylation pattern at maturation-responsive CpG suggested at least partial maturation. Consistent with partial maturation, in gene expression analyses, AML cells expressed high levels of the key lineage-specifying factor CEBPA, but relatively low levels of the key late-differentiation driver CEBPE. In methylation analysis by mass-spectrometry, CEBPE promoter CpG that are usually hypomethylated during granulocyte maturation were significantly hypermethylated in AML cells. Decitabine treatment induced cellular differentiation of AML cells, and the largest methylation decreases were at CpG that are hypomethylated with myeloid maturation, including CEBPE promoter CpG. In contrast, decitabine-treated normal HSC retained immature morphology, and methylation significantly decreased at CpG that are less methylated in immature cells. High expression of lineage-specifying factor and aberrant epigenetic repression of some key late-differentiation genes distinguishes AML cells from normal HSC and could explain the contrasting differentiation and methylation responses to decitabine. PMID:21836612

Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.

PubMed Central

Waugh, W. H.; Daeschner, C. W.; Files, B. A.; McConnell, M. E.; Strandjord, S. E.

2001-01-01

L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated. PMID:11688916

Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.

PubMed

Waugh, W H; Daeschner, C W; Files, B A; McConnell, M E; Strandjord, S E

2001-10-01

L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated.

Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents

PubMed Central

Imokawa, Genji; Ishida, Koichi

2014-01-01

Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and unstimulated level. Thus, owing to the difficulty of confining topical application to a specific hyperpigmented skin area, potent anti-pigmenting agents capable of attenuating the natural unstimulated pigmentation process have the risk of leading to hypopigmentation. Since intracellular signaling pathways within melanocytes do not function substantially in maintaining normal skin color and are activated only by environmental stimuli such as UV radiation, specifically down-regulating the activation of melanogenesis to the constitutive level would be an appropriate strategy to develop new potent anti-pigmenting agents with a low risk of hypopigmentation. In this article, we review the hyperpigmentation mechanisms and intracellular signaling pathways that lead to the stimulation of melanogenesis. We also discuss a screening and evaluation system to select candidates for new anti-melanogenic substances by focusing on inhibitors of endothelin-1 or stem cell factor-triggered intracellular signaling cascades. From this viewpoint, we show that extracts of the herbs Withania somnifera and Melia toosendan and the natural chemicals Withaferin A and Astaxanthin are new candidates for potent anti-pigmenting substances that avoid the risk of hypopigmentation. PMID:24823877

[Phenylketonuria diagnosed during the neonatal period and breast feeding].

PubMed

Cornejo, Verónica; Manríquez, Viviana; Colombo, Marta; Mabe, Paulina; Jiménez, Mónica; De la Parra, Alicia; Valiente, Alf; Raimann, Erna

2003-11-01

Phenylketonuria (PKU) is due to of a defect in the phenylalanine hydroxylase gene (12q22-24.1) leading to hyperphenylalaninemia. Treatment consists in a low phenylalanine (Phe) diet. To evaluate the evolution of early diagnosed PKU children, receiving direct breast feeding, and a special formula without Phe, during their first six months of life. Nineteen PKU children diagnosed in the neonatal period (19.29 +/- 13.8 days of age), treated with breast feeding and formula without Phe since diagnosis, were studied. Intake of calories, proteins and dietary Phe were quantified. Blood Phe, nutritional status and psychomotor development were also measured. The diet that these children received during the 6 months period of study, had a mean of 127 +/- 19.9 Kcal/kg/day, 1.95 +/- 0.3 g protein/kg/day and 35.3 +/- 9.5 mg Phe/kg/day. Fifteen children maintained the blood level of Phe under 8 mg/dl, considered an excellent metabolic control. Only 4 cases had intermittently high levels, between 10-12 mg/dl. At 6 months of age, 74% of the children maintained breast feeding as the only source of Phe. Sixty three percent had a normal nutritional status, 5.2% were at nutritional risk and 31.6% were overweight. Eighty one percent had a normal mental development. The use of direct breast feeding allows a good metabolic control and improves growth and development of early diagnosed PKU children.

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

PubMed

Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

2009-12-01

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

Effect of signal to noise ratio on the speech perception ability of older adults

PubMed Central

Shojaei, Elahe; Ashayeri, Hassan; Jafari, Zahra; Zarrin Dast, Mohammad Reza; Kamali, Koorosh

2016-01-01

Background: Speech perception ability depends on auditory and extra-auditory elements. The signal- to-noise ratio (SNR) is an extra-auditory element that has an effect on the ability to normally follow speech and maintain a conversation. Speech in noise perception difficulty is a common complaint of the elderly. In this study, the importance of SNR magnitude as an extra-auditory effect on speech perception in noise was examined in the elderly. Methods: The speech perception in noise test (SPIN) was conducted on 25 elderly participants who had bilateral low–mid frequency normal hearing thresholds at three SNRs in the presence of ipsilateral white noise. These participants were selected by available sampling method. Cognitive screening was done using the Persian Mini Mental State Examination (MMSE) test. Results: Independent T- test, ANNOVA and Pearson Correlation Index were used for statistical analysis. There was a significant difference in word discrimination scores at silence and at three SNRs in both ears (p≤0.047). Moreover, there was a significant difference in word discrimination scores for paired SNRs (0 and +5, 0 and +10, and +5 and +10 (p≤0.04)). No significant correlation was found between age and word recognition scores at silence and at three SNRs in both ears (p≥0.386). Conclusion: Our results revealed that decreasing the signal level and increasing the competing noise considerably reduced the speech perception ability in normal hearing at low–mid thresholds in the elderly. These results support the critical role of SNRs for speech perception ability in the elderly. Furthermore, our results revealed that normal hearing elderly participants required compensatory strategies to maintain normal speech perception in challenging acoustic situations. PMID:27390712

The Effects of Low Sulfate Concentrations on Modern Microbial Mat Communities: A Long Term Manipulation

NASA Technical Reports Server (NTRS)

Bebout, Brad; Carpenter, Steve; DesMarais, David J.; Discipulo, Mykell; Hogan, Mary; Turk, Kendra

2002-01-01

Microbial mats were widespread during the first ca. 2 Ga. of our biosphere's history. To better understand microbial ecosystems and their biomarkers under the low sulfate levels present in early oceans, we attempted a long-term (ca. 1 year) manipulation of sulfate in modem mats. Mats collected from salt ponds at Guerrero Negro, Baja Calif. Sur were incubated in a Greenhouse "Collaboratory" at Ames. Mats were maintained in artificial seawater brine containing either: 1) sulfate levels normal for these mats (70 mM), or 2) brine in which sulfate was replaced by chloride. Sulfate concentrations in the "low sulfate" brine gradually approached their lowest (to date) value of 0. 1 mM as sulfate was consumed and/or diffused out of the mat over a period of ca. 4 months. During that period of time, a number of differences between the treatments emerged. Relative to the "low sulfate" mats, "normal sulfate" mats had: 1) lower consumption of oxygen in the lower levels of the mat, 2) higher efficiencies of oxygenic photosynthesis, and 3) higher rates of nitrogen fixation. Rates of methane production by the mats increased greatly as sulfate concentrations fell below ca. 0.2 mM. In contrast, "low" and "normal" sulfate mats had similar net rates of exchange of O2 and dissolved inorganic C between the mats and overlying water. Reduced sulfate levels have diverse impacts upon these ecosystems.

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS

PubMed Central

Cardoso, Rodolfo C.; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C.

2016-01-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype. PMID:27792406

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS.

PubMed

Cardoso, Rodolfo C; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C; Padmanabhan, Vasantha

2016-12-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype.

Enhanced angiotensin-converting enzyme activity and systemic reactivity to angiotensin II in normotensive rats exposed to a high-sodium diet

PubMed Central

Crestani, Sandra; Júnior, Arquimedes Gasparotto; Marques, Maria C.A.; Sullivan, Jennifer C.; Webb, R. Clinton; da Silva-Santos, J. Eduardo

2016-01-01

A high salt diet is associated with reduced activity of the renin–angiotensin–aldosterone system (RAAS). However, normotensive rats exposed to high sodium do not show changes in systemic arterial pressure. We hypothesized that, despite the reduced circulating amounts of angiotensin II induced by a high salt diet, the cardiovascular system’s reactivity to angiotensin II is increased in vivo, contributing to maintain arterial pressure at normal levels. Male Wistar rats received chow containing 0.27% (control), 2%, 4%, or 8% NaCl for six weeks. The high-sodium diet did not lead to changes in arterial pressure, although plasma levels of angiotensin II and aldosterone were reduced in the 4% and 8% NaCl groups. The 4% and 8% NaCl groups showed enhanced pressor responses to angiotensin I and II, accompanied by unchanged and increased angiotensin-converting enzyme activity, respectively. The 4% NaCl group showed increased expression of angiotensin II type 1 receptors and reduced expression of angiotensin II type 2 receptors in the aorta. In addition, the hypotensive effect of losartan was reduced in both 4% and 8% NaCl groups. In conclusion these results explain, at least in part, why the systemic arterial pressure is maintained at normal levels in non-salt sensitive and healthy rats exposed to a high salt diet, when the functionality of RAAS appears to be blunted, as well as suggest that angiotensin II has a crucial role in the vascular dysfunction associated with high salt intake, even in the absence of hypertension. PMID:24321189

Insulin resistance and the metabolism of branched-chain amino acids in humans.

PubMed

Adeva, María M; Calviño, Jesús; Souto, Gema; Donapetry, Cristóbal

2012-07-01

Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed.

Proinflammatory state and circulating erythropoietin in persons with and without anemia.

PubMed

Ferrucci, Luigi; Guralnik, Jack M; Woodman, Richard C; Bandinelli, Stefania; Lauretani, Fulvio; Corsi, Anna Maria; Chaves, Paulo H M; Ershler, William B; Longo, Dan L

2005-11-01

High circulating levels of proinflammatory cytokines cause anemia, perhaps by interacting with erythropoietin production or biological activity. We characterize the relationships of systemic inflammation, erythropoietin, and hemoglobin. Data are from the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study population. A sample of 1270 persons aged 65 years or older and 30 men and 30 women from each age-decade 20 to 70 years were randomly selected from the residents in the Chianti, Italy, geographic area. Of the 1714 eligible persons, 1235 had complete data on inflammatory markers, erythropoietin, hemoglobin, potential causes of anemia, and other relevant covariates. Anemia was defined as hemoglobin less than 12 g/dL in women and less than 13 g/dL in men. Independent of age, sex, and hemoglobin, the number of elevated inflammatory markers (C-reactive protein, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha) was associated with progressively higher erythropoietin in non-anemic participants but lower erythropoietin in anemic participants. Findings were consistent across different causes of anemia. The threshold at which the effect of inflammation on erythropoietin reversed was close to 13.0 g/dL of hemoglobin. Our findings suggest that anemia of inflammation evolves from a "pre-anemic" stage characterized by a compensatory increment of erythropoietin that maintains normal hemoglobin levels to a stage of clinically evident anemia in which erythropoietin levels are not high enough to maintain normal hemoglobin, possibly because of the inhibitory effect of inflammation on erythropoietin production. This hypothesis requires testing in a longitudinal study.

Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer

PubMed Central

Timofeeva, Olga A.; Palechor-Ceron, Nancy; Li, Guanglei; Yuan, Hang; Krawczyk, Ewa; Zhong, Xiaogang; Liu, Geng; Upadhyay, Geeta; Dakic, Aleksandra; Yu, Songtao; Fang, Shuang; Choudhury, Sujata; Zhang, Xueping; Ju, Andrew; Lee, Myeong-Seon; Dan, Han C.; Ji, Youngmi; Hou, Yong; Zheng, Yun-Ling; Albanese, Chris; Rhim, Johng; Schlegel, Richard; Dritschilo, Anatoly; Liu, Xuefeng

2017-01-01

Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient's prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. Characterization of cells with DNA fingerprinting demonstrated identical patterns in normal and tumor CR cells as well as in xenografted tumors. By flow cytometry, both normal and tumor CR cells expressed basal, luminal, and stem cell markers, with the majority of the normal and tumor CR cells expressing prostate basal cell markers, CD44 and Trop2, as well as luminal marker, CD13, suggesting a transit-amplifying phenotype. Consistent with this phenotype, real time RT-PCR analyses demonstrated that CR cells predominantly expressed high levels of basal cell markers (KRT5, KRT14 and p63), and low levels of luminal markers. When the CR tumor cells were injected into SCID mice, the expression of luminal markers (AR, NKX3.1) increased significantly, while basal cell markers dramatically decreased. These data suggest that CR cells maintain high levels of proliferation and low levels of differentiation in the presence of feeder cells and ROCK inhibitor, but undergo differentiation once injected into SCID mice. Genomic analyses, including SNP and INDEL, identified genes mutated in tumor cells, including components of apoptosis, cell attachment, and hypoxia pathways. The use of matched patient-derived cells provides a unique in vitro model for studies of early prostate cancer. PMID:28009986

Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase.

PubMed

Yong, Kok Pin; Tan, Ban Hock; Low, Chian Yong

2012-12-20

Acute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK). A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus. In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

Sertoli cell-specific ablation of miR-17-92 cluster significantly alters whole testis transcriptome without apparent phenotypic effects.

PubMed

Hurtado, Alicia; Real, Francisca M; Palomino, Rogelio; Carmona, Francisco David; Burgos, Miguel; Jiménez, Rafael; Barrionuevo, Francisco J

2018-01-01

MicroRNAs are frequently organized into polycistronic clusters whose transcription is controlled by a single promoter. The miR-17-92 cluster is expressed in most embryonic and postnatal organs. It is a potent oncogene associated to several types of cancer and it is involved in several important developmental processes. In the testis, expression of the miR-17-92 cluster in the germ cells is necessary to maintain normal spermatogenesis. This cluster is also expressed in Sertoli cells (the somatic cells of the seminiferous tubules), which require miRNAs for correct cell development and survival. To study the possible role of miR-17-92 in Sertoli cell development and function and, in order to overcome the postnatal lethality of miR-17-92-/ mice, we conditionally deleted it in embryonic Sertoli cells shortly after the sex determination stage using an Amh-Cre allele. Mutant mice developed apparently normal testes and were fertile, but their testis transcriptomes contained hundreds of moderately deregulated genes, indicating that testis homeostasis is tightly controlled in mammals and that miR-17-92 expression in Sertoli cells contribute to maintain normal gene expression levels, but is unnecessary for testis development and function. Our results show that significant deregulation of hundreds of genes might have no functional consequences.

The experience of weight management in normal weight adults.

PubMed

Hernandez, Cheri Ann; Hernandez, David A; Wellington, Christine M; Kidd, Art

2016-11-01

No prior research has been done with normal weight persons specific to their experience of weight management. The purpose of this research was to discover the experience of weight management in normal weight individuals. Glaserian grounded theory was used. Qualitative data (focus group) and quantitative data (food diary, study questionnaire, and anthropometric measures) were collected. Weight management was an ongoing process of trying to focus on living (family, work, and social), while maintaining their normal weight targets through five consciously and unconsciously used strategies. Despite maintaining normal weights, the nutritional composition of foods eaten was grossly inadequate. These five strategies can be used to develop new weight management strategies that could be integrated into existing weight management programs, or could be developed into novel weight management interventions. Surprisingly, normal weight individuals require dietary assessment and nutrition education to prevent future negative health consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment-resistant depressed patients show a good response to Mindfulness-based Cognitive Therapy

PubMed Central

Kenny, M.A.; Williams, J.M.G.

2007-01-01

Mindfulness-based Cognitive Therapy (MBCT) is a class-based programme designed for use in the prevention of relapse of major depression. Its aim is to teach participants to disengage from those cognitive processes that may render them vulnerable to future episodes. These same cognitive processes are also known to maintain depression once established, hence a clinical audit was conducted to explore the use of MBCT in patients who were currently actively depressed, and who had not responded fully to standard treatments. The study showed that it was acceptable to these patients and resulted in an improvement in depression scores (pre-post Effect Size=1.04), with a significant proportion of patients returning to normal or near-normal levels of mood. PMID:16797486

The last common ancestor of animals lacked the HIF pathway and respired in low-oxygen environments

PubMed Central

Vargas, Sergio; Larsen, Morten; Elemans, Coen PH; Canfield, Donald E

2018-01-01

Animals have a carefully orchestrated relationship with oxygen. When exposed to low environmental oxygen concentrations, and during periods of increased energy expenditure, animals maintain cellular oxygen homeostasis by enhancing internal oxygen delivery, and by enabling the anaerobic production of ATP. These low-oxygen responses are thought to be controlled universally across animals by the hypoxia-inducible factor (HIF). We find, however, that sponge and ctenophore genomes lack key components of the HIF pathway. Since sponges and ctenophores are likely sister to all remaining animal phyla, the last common ancestor of extant animals likely lacked the HIF pathway as well. Laboratory experiments show that the marine sponge Tethya wilhelma maintains normal transcription under oxygen levels down to 0.25% of modern atmospheric saturation, the lowest levels we investigated, consistent with the predicted absence of HIF or any other HIF-like pathway. Thus, the last common ancestor of all living animals could have metabolized aerobically under very low environmental oxygen concentrations. PMID:29402379

[Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

PubMed

Ren, Si-Hua; He, Yu-Xin; Ma, Yi-Ran; Jin, Jing-Chun; Kang, Dan

2016-02-01

To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

Reversible brain atrophy in glutaric aciduria type 1.

PubMed

Numata-Uematsu, Yurika; Sakamoto, Osamu; Kakisaka, Yosuke; Okubo, Yukimune; Oikawa, Yoshitsugu; Arai-Ichinoi, Natsuko; Kure, Shigeo; Uematsu, Mitsugu

2017-06-01

Glutaric aciduria type 1 (GA1) is a rare metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase. The typical clinical onset features an acute encephalopathic crisis developed in early childhood, causing irreversible striatal injury. Recently, tandem mass spectrometry of spots of dried blood has allowed pre-symptomatic detection of GA1 in newborns. Early treatment can prevent irreversible neurological injury. We report the case of a girl with GA1 who exhibited a characteristic reversible change upon brain magnetic resonance imaging (MRI). She was diagnosed with GA1 as a newborn. She commenced dietary carnitine and her intake of lysine and tryptophan were reduced at the age of 4weeks. After treatment commenced, her mean glutarylcarnitine level was lower than that in the previous reports. The plasma lysine and tryptophan levels were maintained below the normal ranges. At 4months, brain MRI revealed a widened operculum with dilatation of the subarachnoid spaces surrounding the atrophic bilateral frontotemporal lobes; this is typical of GA1 patients. However, at 17months, MRI revealed that the atrophic lesion had disappeared and she subsequently underwent normal maturation. She has never suffered a metabolic decompensation episode. At 26months, her development and brain MRI were normal. The present reversible brain atrophy in a patient with GA1 indicates that early dietary modifications with a lower level of glutarylcarnitine and administration of carnitine can lead to normal development. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Increased efficiency of gamma-irradiated versus mitomycin C-treated feeder cells for the expansion of normal human cells in long-term cultures.

PubMed

Roy, A; Krzykwa, E; Lemieux, R; Néron, S

2001-12-01

Several normal human cells, such as hematopoietic stem cells, dendritic cells, and B cells, can be cultured in vitro in defined optimal conditions. Several ex vivo culture systems require the use of feeder cells to support the growth of target cells. In such systems, proliferation of feeder cells has to be stopped, so that they can be used as nonreplicating viable support cells. Because feeder cells need to provide one or few active signals, it is important to maintain them in an metabolically active state, allowing continued expression of specific ligands or cytokines. Mitomycin C and gamma-irradiation treatments are commonly used to prepare nonproliferating feeder cells and are usually considered to be equivalent. Normal human B lymphocytes can be expanded in vitro in the presence of feeder cells expressing the CD40 ligand CD154. Here we compared the ability of gamma-irradiation- and mitomycin C-treated feeder cells to support the expansion of normal human B lymphocytes. The results indicate that expansion of B cells during a long-term culture was 100 times more potent using gamma-irradiated feeder cells compared to mitomycin C-treated cells. This difference could be related to a significant reduction in both cellular metabolism and level of CD154 expression observed in mitomycin C-treated feeder cells, but not in gamma-irradiated cells nor in control untreated cells. These results indicate that mitomycin C-treated feeder cells are metabolically altered, and consequently less efficient at maintaining cell expansion in the long-term cell culture system used.

Behavioral and Electrophysiological Characterization of Dyt1 Heterozygous Knockout Mice

PubMed Central

Yokoi, Fumiaki; Chen, Huan-Xin; Dang, Mai Tu; Cheetham, Chad C.; Campbell, Susan L.; Roper, Steven N.; Sweatt, J. David; Li, Yuqing

2015-01-01

DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinAΔE). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs) and normal theta-burst-induced long-term potentiation (LTP) in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinAΔE does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO) mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs) were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia. PMID:25799505

Behavioral and electrophysiological characterization of Dyt1 heterozygous knockout mice.

PubMed

Yokoi, Fumiaki; Chen, Huan-Xin; Dang, Mai Tu; Cheetham, Chad C; Campbell, Susan L; Roper, Steven N; Sweatt, J David; Li, Yuqing

2015-01-01

DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinA(ΔE)). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs) and normal theta-burst-induced long-term potentiation (LTP) in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinA(ΔE) does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO) mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs) were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia.

[Immunoloical aspects of the antropogenic response to the antigens of symbiotic non-toxigenic diphtherial corynebacteria].

PubMed

Shmeleva, E A; Popkova, S M; Makarova, S I; Baturina, I G

2006-01-01

Corynebacteria, being ancient symbionts of open cavities of human body, carry unique, balanced immunogenic stimuli, formed in the process of evolution, thus maintaining non-specific resistance at a certain level. They favor formation of human microcenotic communities as a normal biological and physiological phenomenon. Codivak, a preparation of natural antigens of a symbiotic strain of non-toxigenic diphtherial corynebacteria, is able to correct not only disturbances of oropharyngeal immunity, but also general cell-mediated and humoral immunity disorders.

Recovery of short-term memory and psychomotor speed but not postural stability with long-term sobriety in alcoholic women.

PubMed

Rosenbloom, Margaret J; Pfefferbaum, Adolf; Sullivan, Edith V

2004-07-01

The authors assessed effects of extended abstinence on cognitive and motor function deficits previously observed in a group of alcoholic women (n = 43) initially tested after 15 weeks of sobriety. Alcoholic women were retested 1 and 4 years later, and control women were retested 3 years later. At Year 1, 14 of 23 returners had maintained sobriety, but they did not perform significantly better than relapsers; the group as a whole continued to show deficits relative to age norms. By Year 4, 13 of 14 returners had maintained sobriety for more than 30 months; as a group, these women had returned to normal levels on tests of memory and psychomotor speed but remained impaired in standing balance.

Regulation of food intake and obesity.

PubMed

Mayer, J; Thomas, D W

1967-04-21

This is not the place to consider the medical significance of obesity in terms of conditions such as heart disease and hypertension, diabetes, and arthritis. These very complex interrelationships have been dealt with elsewhere (69). We hope that enough evidence has been presented to demonstrate that energy balance is normally maintained by a precise and reliable physiologic mechanism, and that the energy surplus represented by obesity may reflect direct failure of this mechanism or some combination from a variety of neurological, endocrine, enzymatic, and psychological disorders. Environmental conditions as well as genetic and traumatic factors may contribute to the development of obesity. If increasing mechanization brings tus below the level of energy expenditure at which food intake is properly regulated, appropriate habits of exercise will have to be established and maintained.

Oil cooling system for a gas turbine engine

NASA Technical Reports Server (NTRS)

Coffinberry, G. A.; Kast, H. B. (Inventor)

1977-01-01

A gas turbine engine fuel delivery and control system is provided with means to recirculate all fuel in excess of fuel control requirements back to aircraft fuel tank, thereby increasing the fuel pump heat sink and decreasing the pump temperature rise without the addition of valving other than that normally employed. A fuel/oil heat exchanger and associated circuitry is provided to maintain the hot engine oil in heat exchange relationship with the cool engine fuel. Where anti-icing of the fuel filter is required, means are provided to maintain the fuel temperature entering the filter at or above a minimum level to prevent freezing thereof. Fluid circuitry is provided to route hot engine oil through a plurality of heat exchangers disposed within the system to provide for selective cooling of the oil.

Interplay between population firing stability and single neuron dynamics in hippocampal networks

PubMed Central

Slomowitz, Edden; Styr, Boaz; Vertkin, Irena; Milshtein-Parush, Hila; Nelken, Israel; Slutsky, Michael; Slutsky, Inna

2015-01-01

Neuronal circuits' ability to maintain the delicate balance between stability and flexibility in changing environments is critical for normal neuronal functioning. However, to what extent individual neurons and neuronal populations maintain internal firing properties remains largely unknown. In this study, we show that distributions of spontaneous population firing rates and synchrony are subject to accurate homeostatic control following increase of synaptic inhibition in cultured hippocampal networks. Reduction in firing rate triggered synaptic and intrinsic adaptive responses operating as global homeostatic mechanisms to maintain firing macro-stability, without achieving local homeostasis at the single-neuron level. Adaptive mechanisms, while stabilizing population firing properties, reduced short-term facilitation essential for synaptic discrimination of input patterns. Thus, invariant ongoing population dynamics emerge from intrinsically unstable activity patterns of individual neurons and synapses. The observed differences in the precision of homeostatic control at different spatial scales challenge cell-autonomous theory of network homeostasis and suggest the existence of network-wide regulation rules. DOI: http://dx.doi.org/10.7554/eLife.04378.001 PMID:25556699

The effects of fetal and perinatal asphyxia on neuronal cytokine levels and ceramide metabolism in adulthood.

PubMed

Vlassaks, Evi; Gavilanes, Antonio W D; Vles, Johan S H; Deville, Sarah; Kramer, Boris W; Strackx, Eveline; Martinez-Martinez, Pilar

2013-02-15

In a rat model of global fetal and perinatal asphyxia, we investigated if asphyxia and long-lasting brain tolerance to asphyxia (preconditioning) are mediated by modifications in inflammatory cytokines and ceramide metabolism genes in prefrontal cortex, hippocampus and caudate-putamen at the age of 8months. Most significant changes were found in prefrontal cortex, with reduced LAG1 homolog ceramide synthase 1 expression after both types of asphyxia. Additionally, sphingosine kinase 1 was upregulated in those animals that experienced the combination of fetal and perinatal asphyxia (preconditioning), suggesting increased cell proliferation. While cytokine levels are normal, levels of ceramide genes were modulated both after fetal and perinatal asphyxia in the adult prefrontal cortex. Moreover, the combination of two subsequent asphyctic insults provides long-lasting neuroprotection in the prefrontal cortex probably by maintaining normal apoptosis and promoting cell proliferation. Better understanding of the effects of asphyxia on ceramide metabolism will help to understand the changes leading to brain tolerance and will open opportunities for the development of new neuroprotective therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

The effects of in-flight treadmill exercise on postflight orthostatic tolerance

NASA Technical Reports Server (NTRS)

Siconolfi, Steven F.; Charles, John B.

1992-01-01

In-flight aerobic exercise is thought to decrease the deconditioning effects of microgravity. Two deconditioning characteristics are the decreases in aerobic capacity (maximum O2 uptake) and an increased cardiovascular response to orthostatic stress (supine to standing). Changes in both parameters were examined after Shuttle flights of 8 to 11 days in astronauts who performed no in-flight exercise, a lower than normal volume of exercise, and a near-normal volume of exercise. The exercise regimen was a traditional continuous protocol. Maximum O2 uptake was maintained in astronauts who completed a near-normal exercise volume of in-flight exercise. Cardiovascular responses to stand test were equivocal among the groups. The use of the traditional exercise regimen as a means to maintain adequate orthostatic responses produced equivocal responses. A different exercise prescription may be more effective in maintaining both exercise capacity and orthostatic tolerance.

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

Resistance training attenuates fat mass regain after weight loss in ovariectomized rats.

PubMed

Pighon, Abdolnaser; Paquette, Amélie; Barsalani, Razieh; Chapados, Natalie Ann; Rabasa-Lhoret, Rémi; Yasari, Siham; Prud'homme, Denis; Lavoie, Jean-Marc

2009-09-20

The aim of the present study was to investigate the effects of maintaining only one of the two components of a food restriction (FR)+resistance training (RT) regimen on the regain of body weight and fat mass (liver and adipocytes) in ovariectomized (Ovx) rats. Five week Ovx rats were submitted to a weight loss program consisting of a 26% FR combined with RT (OvxFR+RT) for 8 weeks. RT consisted of climbing a 1.5m vertical grid with a load attached to the tail, 20-40 times with progressively increasing loads 4 times/week. Following this weight loss intervention, OvxFR+RT rats were sub-divided into 3 groups for an additional 5 weeks: 2 groups went back to a normal ad libitum feeding with or without RT and the other group kept only FR. Combined FR+RT program in Ovx rats led to lower body mass gain, liver triacylglycerol (TAG) levels, and fat mass gain compared to sedentary normally fed Ovx rats (P<0.01). Stopping both FR and RT over a 5 week period resulted in the regain of body weight, intra-abdominal fat pad weight and liver TAG (P<0.01). When only FR was maintained, the regain of body and fat pad weight as well as liver and plasma TAG concentrations was completely prevented. However, when only RT was maintained, regain in the aforementioned parameters was attenuated but not prevented (P<0.05). It is concluded that following a FR+RT weight loss program, continuation of only RT constitutes an asset to attenuate body weight and fat mass regain in Ovx rats; although the impact is less than the maintaining FR alone. These results suggest that, in post-menopausal women, RT is a positive strategy to reduce body weight and fat mass relapse.

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

PubMed

Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

2018-01-20

The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

Regulation of WNT Signaling at the Neuromuscular Junction by the Immunoglobulin Superfamily Protein RIG-3 in Caenorhabditis elegans

PubMed Central

Pandey, Pratima; Bhardwaj, Ashwani; Babu, Kavita

2017-01-01

Perturbations in synaptic function could affect the normal behavior of an animal, making it important to understand the regulatory mechanisms of synaptic signaling. Previous work has shown that in Caenorhabditis elegans an immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to maintain normal acetylcholine receptor levels at the neuromuscular junction (NMJ). In this study, we elucidate the molecular and functional mechanism of RIG-3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation) assays that presynaptic RIG-3 functions by directly interacting with the immunoglobulin domain of the nonconventional Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles. This interaction in turn inhibits Wnt/LIN-44 signaling through the ROR/CAM-1 receptor, and allows for maintenance of normal acetylcholine receptor, AChR/ACR-16, levels at the neuromuscular synapse. Further, this work reveals that RIG-3 and ROR/CAM-1 function through the β-catenin/HMP-2 at the NMJ. Taken together, our results demonstrate that RIG-3 functions as an inhibitory molecule of the Wnt/LIN-44 signaling pathway through the RTK, CAM-1. PMID:28515212

Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS).

PubMed

Bowers, A S; Pepple, D J; Reid, H L

2011-01-01

The determination of an optimal haematocrit (H0) has important clinical implications if such a level can be attained, and more importantly, maintained. This is defined as a haematocrit level, above or below which oxygen delivery is deleteriously affected. This study is designed to determine an optimal haematocrit in normal (AA), sickle cell trait (AS) and sickle cell disease (SS) subjects. Twenty-seven apparently healthy subjects having normal haemoglobin genotype, 24 with sickle cell trait and 42 with homozygous sickle cell disease were recruited into the study. Whole blood viscosity (WBV) was measured by a Wells Brookfield Cone and Plate Viscometer at a shear rate of 230 sec-1. Haematocrit was determined by an AC.Tron Coulter Counter. The optimal haematocrit was calculated as the inverse of a constant, K, which was derived from the haematocrit and viscosity data. Our findings showed that the H0 varied significantly among the 3 haemoglobin genotypes, in the order AA vs SS and AS vs SS. Additionally, the data indicated an increased H0 in subjects with sickle cell trait, suggesting a possible impairment in oxygen delivery in these individuals.

Impairment of short-term memory associated with low iron stores in a volunteer multidose plateletpheresis donor.

PubMed

Page, E A; Harrison, J F; Jaldow, E J; Kopelman, M

2008-10-01

A platelet donor may lose 80-100 mL of blood both in the harness and by blood sampling at each donation, the equivalent of four to five whole blood donations per annum for a donor attending at 2-weekly intervals. A 54-year-old male multidose platelet donor had donated platelets at regular 2-weekly intervals for 6 years. He developed an impairment of anterograde memory (new learning). A self-rating scale revealed a moderate degree of depression [Beck Depression Inventory (BDI) score 22]. Memory testing (Doors and People Memory Battery) showed low scores, particularly for verbal recall and verbal recognition memory. He was found to have a normal haemoglobin of 157 g L(-1) with normal red blood cell indices, but a low serum ferritin (15 ng mL(-1)) and a low serum iron (8.1 mmol L(-1)). Following iron therapy and a return of his iron stores to normal levels, there was an improved BDI score of 13 (minimal level of depression) and a marked improvement in memory test scores. This has been maintained even though he has resumed platelet donation but at reduced intervals.

The influence of hunger on meal to pellet intervals in barred owls

USGS Publications Warehouse

Duke, G.E.; Fuller, M.R.; Huberty, B.J.

1980-01-01

1. Barred owls fed at a sub-maintenance (SM) level had significantly (P < 0.01) longer meal to pellet intervals (MPI)/g eaten/kg body weight (BW) than those fed at an above maintenance (AM) level; MPI/g per kg for owls fed at a maintenance (M) level was intermediate but significantly (P < 0.01) different from both SM and AM.2. During SM feeding, MPI/g per kg gradually increased.3. The proportion of a meal occurring in a pellet was less in “hungry” owls whether losing weight (SM) or gaining (AM) as compared to owls maintaining their normal body weight (M).4. SM fed owls appear to be able to increase digestion time as well as thoroughness of digestion.

Contaminant studies in the Sierra Nevadas

USGS Publications Warehouse

Sparling, Don; Fellers, Gary M.

2002-01-01

1. 1. Barred owls fed at a sub-maintenance (SM) level had significantly (P < 0.01) longer meal to pellet intervals (MPI)/g eaten/kg body weight (BW) than those fed at an above maintenance (AM) level; MPI/g per kg for owls fed at a maintenance (M) level was intermediate but significantly (P < 0.01) different from both SM and AM. 2. 2. During SM feeding, MPI/g per kg gradually increased. 3. 3. The proportion of a meal occurring in a pellet was less in ?hungry? owls whether losing weight (SM) or gaining (AM) as compared to owls maintaining their normal body weight (M). 4. 4. SM fed owls appear to be able to increase digestion time as well as thoroughness of digestion.

Three-Dimensional mRNA Measurements Reveal Minimal Regional Heterogeneity in Esophageal Squamous Cell Carcinoma

PubMed Central

Yan, Wusheng; Shih, Joanna; Rodriguez-Canales, Jaime; Tangrea, Michael A.; Player, Audrey; Diao, Lixia; Hu, Nan; Goldstein, Alisa M.; Wang, Jing; Taylor, Philip R.; Lippman, Scott M.; Wistuba, Ignacio I.; Emmert-Buck, Michael R.; Erickson, Heidi S.

2014-01-01

The classic tumor clonal evolution theory postulates that cancers change over time to produce unique molecular subclones within a parent neoplasm, presumably including regional differences in gene expression. More recently, however, this notion has been challenged by studies showing that tumors maintain a relatively stable transcript profile. To examine these competing hypotheses, we microdissected discrete subregions containing approximately 3000 to 8000 cells (500 to 1500 μm in diameter) from ex vivo esophageal squamous cell carcinoma (ESCC) specimens and analyzed transcriptomes throughout three-dimensional tumor space. Overall mRNA profiles were highly similar in all 59 intratumor comparisons, in distinct contrast to the markedly different global expression patterns observed in other dissected cell populations. For example, normal esophageal basal cells contained 1918 and 624 differentially expressed genes at a greater than twofold level (95% confidence level of <5% false positives), compared with normal differentiated esophageal cells and ESCC, respectively. In contrast, intratumor regions had only zero to four gene changes at a greater than twofold level, with most tumor comparisons showing none. The present data indicate that, when analyzed using a standard array-based method at this level of histological resolution, ESCC contains little regional mRNA heterogeneity. PMID:23219752

Overcoming reprogramming resistance of Fanconi anemia cells

PubMed Central

Müller, Lars U. W.; Milsom, Michael D.; Harris, Chad E.; Vyas, Rutesh; Brumme, Kristina M.; Parmar, Kalindi; Moreau, Lisa A.; Schambach, Axel; Park, In-Hyun; London, Wendy B.; Strait, Kelly; Schlaeger, Thorsten; DeVine, Alexander L.; Grassman, Elke; D'Andrea, Alan; Daley, George Q.

2012-01-01

Fanconi anemia (FA) is a recessive syndrome characterized by progressive fatal BM failure and chromosomal instability. FA cells have inactivating mutations in a signaling pathway that is critical for maintaining genomic integrity and protecting cells from the DNA damage caused by cross-linking agents. Transgenic expression of the implicated genes corrects the phenotype of hematopoietic cells, but previous attempts at gene therapy have failed largely because of inadequate numbers of hematopoietic stem cells available for gene correction. Induced pluripotent stem cells (iPSCs) constitute an alternate source of autologous cells that are amenable to ex vivo expansion, genetic correction, and molecular characterization. In the present study, we demonstrate that reprogramming leads to activation of the FA pathway, increased DNA double-strand breaks, and senescence. We also demonstrate that defects in the FA DNA-repair pathway decrease the reprogramming efficiency of murine and human primary cells. FA pathway complementation reduces senescence and restores the reprogramming efficiency of somatic FA cells to normal levels. Disease-specific iPSCs derived in this fashion maintain a normal karyotype and are capable of hematopoietic differentiation. These data define the role of the FA pathway in reprogramming and provide a strategy for future translational applications of patient-specific FA iPSCs. PMID:22371882

High activity of mitochondrial glycerophosphate dehydrogenase and glycerophosphate-dependent ROS production in prostate cancer cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, Subir K.R.; Department of Pathology and Molecular Medicine, McMaster University, 1200 Main St. West, Hamilton, Ont., L8N 3Z5; Gemin, Adam

Most malignant cells are highly glycolytic and produce high levels of reactive oxygen species (ROS) compared to normal cells. Mitochondrial glycerophosphate dehydrogenase (mGPDH) participates in the reoxidation of cytosolic NADH by delivering reducing equivalents from this molecule into the electron transport chain, thus sustaining glycolysis. Here, we investigate the role of mGPDH in maintaining an increased rate of glycolysis and evaluate glycerophosphate-dependent ROS production in prostate cancer cell lines (LNCaP, DU145, PC3, and CL1). Immunoblot, polarographic, and spectrophotometric analyses revealed that mGPDH abundance and activity was significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelialmore » cell line PNT1A. Furthermore, both the glycolytic capacity and glycerophosphate-dependent ROS production was increased 1.68- to 4.44-fold and 5- to 7-fold, respectively, in prostate cancer cell lines when compared to PNT1A cells. Overall, these data demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to ROS production in prostate cancer cells.« less

Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with Synaptic Proteins

PubMed Central

Jones, Kelly A.; Kopeikina, Katherine J.; Burette, Alain C.; Copits, Bryan A.; Forrest, Marc P.; Fawcett-Patel, Jessica M.

2017-01-01

Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded by CDH10 within the ASD risk locus 5p14.1, maintains both excitatory and inhibitory synaptic scaffold structure in cultured cortical neurons from rats of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses in neocortex, where it is organized into nanoscale puncta that influence the size of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but increases inhibitory synapse size and strength, altering the E/I ratio in cortical neurons. Furthermore, cadherin-10 exhibits differential participation in complexes with PSD-95 and gephyrin, which may underlie its role in maintaining the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a common ASD risk factor controls E/I ratios by regulating excitatory and inhibitory synapses in opposing directions. SIGNIFICANCE STATEMENT The correct balance between excitatory/inhibitory (E/I) is crucial for normal brain function and is altered in psychiatric disorders such as autism. However, the molecular mechanisms that underlie this balance remain elusive. To address this, we studied cadherin-10, an adhesion protein that is genetically linked to autism and understudied at the cellular level. Using a combination of advanced microscopy techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta at excitatory and inhibitory synapses, maintains excitatory and inhibitory synaptic structure, and is essential for maintaining the correct balance between excitation and inhibition in neuronal dendrites. These findings reveal a new mechanism by which E/I balance is controlled in neurons and may bear relevance to synaptic dysfunction in autism. PMID:29030434

Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia.

PubMed

Carlsson, Göran; Wahlin, Ylva-Britt; Johansson, Anders; Olsson, Anders; Eriksson, Torbjörn; Claesson, Rolf; Hänström, Lennart; Henter, Jan-Inge

2006-04-01

Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

The Dinoflagellate Lingulodinium polyedrum Responds to N Depletion by a Polarized Deposition of Starch and Lipid Bodies

PubMed Central

Dagenais Bellefeuille, Steve; Dorion, Sonia; Rivoal, Jean; Morse, David

2014-01-01

Dinoflagellates are important contributors to the marine phytoplankton and global carbon fixation, but are also infamous for their ability to form the spectacular harmful algal blooms called red tides. While blooms are often associated with high available nitrogen, there are instances where they are observed in oligotrophic environments. In order to maintain their massive population in conditions of nitrogen limitation, dinoflagellates must have evolved efficient adaptive mechanisms. Here we report the physiological responses to nitrogen deprivation in Lingulodinium polyedrum. We find that this species reacts to nitrogen stress, as do most plants and microalgae, by stopping cell growth and diminishing levels of internal nitrogen, in particular in the form of protein and chlorophyll. Photosynthesis is maintained at high levels for roughly a week following nitrate depletion, resulting in accumulated photosynthetic products in the form of starch. During the second week, photosynthesis rates decrease due to a reduction in the number of chloroplasts and the accumulation of neutral lipid droplets. Surprisingly, the starch granules and lipid droplets are seen to accumulate at opposite poles of the cell. Lastly, we observe that cells acclimated to nitrogen-depleted conditions resume normal growth after addition of inorganic nitrogen, but are able to maintain high cell densities far longer than cells grown continuously in nitrogen-replete conditions. PMID:25368991

Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

PubMed

Tavakoli, Naser; Minaiyan, Mohsen; Tabbakhian, Majid; Pendar, Yaqub

2014-01-01

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.

Clinical risk factors demonstrate an age-dependent relationship with oxidative stress biomarkers in African Americans.

PubMed

Sturgeon, Kathleen M; Feairheller, Deborah L; Diaz, Keith M; Williamson, Sheara T; Veerabhadrappa, Praveen; Brown, Michael D

2010-01-01

To examine the interaction of oxidative stress biomarkers with age, and also factors that influence oxidative stress such as body mass index (BMI) and fitness in a population of individuals with established higher risk of cardiovascular disease, African Americans. Blood samples were obtained from healthy college-age and middle-age to older African Americans. Participants underwent a graded exercise test. Superoxide dismutase (SOD) activity, total antioxidant capacity and thiobarbituric acid reactive substances (TBARS) levels were measured. TBARS levels were significantly (P = .001) lower in young participants relative to middle-age to older participants. SOD activity was significantly (P = .001) lower in middle-age to older participants with low fitness relative to participants with normal fitness, and lower (P = .04) in middle-age to older participants that were overweight relative to normal weight participants. In a healthy middle-age to older population of African Americans, BMI and fitness are crucial for maintaining a healthy endothelium.

Free Thyroxine and Functional Mobility, Fitness, and Fatigue in Euthyroid Older Men and Women in the Baltimore Longitudinal Study of Aging.

PubMed

Simonsick, Eleanor M; Chia, Chee W; Mammen, Jennifer S; Egan, Josephine M; Ferrucci, Luigi

2016-07-01

Emerging evidence suggests that mildly down-regulated thyroid function in older persons may protect and/or reflect maintained health. Using observational data collected between January 2006 and March 2014 on a volunteer sample of 602 men and women aged 68-97 years with normal thyroid function participating in the Baltimore Longitudinal Study of Aging, this study examines the concurrent relationship between reported walking ability, usual and rapid gait speed, endurance walk performance, fatigability, and reported energy level with respect to free thyroxine (FT4) within the normal range (0.76-1.50ng/dL) as a continuous variable and categorized as low (lower quartile), medium (interquartile), or high (upper quartile). Adjusting for sex, age, race, height, weight, exercise and smoking, reported walking ability, usual and rapid gait speed, 400-m time, fatigability, and reported energy level were less favorable with increasing FT4 (p = .013 to <.001). In sex-strata, similar associations were observed except for walking ability in men and energy level in women. Categorical analyses revealed that persons with low FT4 exhibited better functional mobility, fitness, and reported energy than persons with intermediate or high levels (p < .05 for all). Persons with high-normal versus medium FT4 had slower usual and rapid gait speed (p < .05) only. Older adults with low-normal FT4 exhibit better mobility, fitness, and fatigue profiles. Mildly down-regulated thyroid function appears to align with better function in old age and may serve as a biomarker of healthy longevity. Published by Oxford University Press on behalf of the Gerontological Society of America 2016.

Efficacy of brown seaweed hot water extract against HCl-ethanol induced gastric mucosal injury in rats.

PubMed

Raghavendran, Hanumantha Rao Balaji; Sathivel, Arumugam; Devaki, Thiruvengadam

2004-04-01

Effect of pre-treatment with hot water extract of marine brown alga Sargassum polycystum C.Ag. (100 mg/kg body wt, orally for period of 15 days) on HCl-ethanol (150 mM of HCl-ethanol mixture containing 0.15 N HCl in 70% v/v ethanol given orally) induced gastric mucosal injury in rats was examined with respect to lipid peroxides, antioxidant enzyme status, acid/pepsin and glycoproteins in the gastric mucosa. The levels of lipid peroxides of gastric mucosa and volume, acidity of the gastric juice were increased with decreased levels of antioxidant enzymes and glycoproteins were observed in HCl-ethanol induced rats. The rats pre-treated with seaweed extract prior to HCl-ethanol induction reversed the depleted levels of antioxidant enzymes and reduced the elevated levels of lipid peroxides when compared with HCl-ethanol induced rats. The levels of glycoproteins and alterations in the gastric juice were also maintained at near normal levels in rats pre-treated with seaweed extract. The rats given seaweed extract alone did not show any toxicity, which was confirmed by histopathological studies. These results suggest that the seaweed extract contains some anti-ulcer agents, which may maintain the volume/acidity of gastric juice and improve the gastric mucosa antioxidant defense system against HCl-ethanol induced gastric mucosal injury in rats.

Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation.

PubMed

Badr, Haitham A; AlSadek, Dina M M; Mathew, Mohit P; Li, Chen-Zhong; Djansugurova, Leyla B; Yarema, Kevin J; Ahmed, Hafiz

2015-11-01

Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Quantitative analysis method based on fractal theory for medical imaging of normal brain development in infants].

PubMed

Li, Heheng; Luo, Liangping; Huang, Li

2011-02-01

The present paper is aimed to study the fractal spectrum of the cerebral computerized tomography in 158 normal infants of different age groups, based on the calculation of chaotic theory. The distribution range of neonatal period was 1.88-1.90 (mean = 1.8913 +/- 0.0064); It reached a stable condition at the level of 1.89-1.90 during 1-12 months old (mean = 1.8927 +/- 0.0045); The normal range of 1-2 years old infants was 1.86-1.90 (mean = 1.8863 +/- 4 0.0085); It kept the invariance of the quantitative value among 1.88-1.91(mean = 1.8958 +/- 0.0083) during 2-3 years of age. ANOVA indicated there's no significant difference between boys and girls (F = 0.243, P > 0.05), but the difference of age groups was significant (F = 8.947, P < 0.001). The fractal dimension of cerebral computerized tomography in normal infants computed by box methods was maintained at an efficient stability from 1.86 to 1.91. It indicated that there exit some attractor modes in pediatric brain development.

High-dose oral colecalciferol loading in obesity: impact of body mass index and its utility prior to bariatric surgery to treat vitamin D deficiency.

PubMed

King, R J; Chandrajay, D; Abbas, A; Orme, S M; Barth, J H

2017-04-01

Obesity is associated with lower vitamin D levels compared with normal weight subjects, and if levels are not replaced prior to bariatric surgery, this can increase fracture risk as bone density typically falls post-operatively. We analysed the effect of body mass index (BMI) on vitamin D levels in response to 300 000 IU of colecalciferol in patients with vitamin D deficiency (<30 nmol L -1 ). Patients were grouped according to their BMI as normal weight (20-24.9 kg m -2 ), overweight (25-29.9 kg m -2 ), obese class I (30-34.9 kg m -2 ) and obese class II and above (>35 kg m -2 ). The records were retrospectively analysed to investigate the effects of BMI on vitamin D (total 25-hydroxy vitamin D [25(OH)D]), serum Ca 2+ and parathyroid hormone (PTH) levels at 6, 12, 26 and 52 weeks compared with baseline. Compared with normal weight subjects, overweight and obese patients achieved lower mean peak total 25(OH)D levels (6 weeks post-loading), which was most significant in the class II and above group (mean total 25(OH)D levels 96.5 ± 24.2 nmol L -1 and 72.42 ± 24.9 nmol L -1 , respectively; P = 0.003). By 26 weeks, total 25(OH)D levels fell in all groups; however, there was now a significant difference between the normal weight subjects and all other groups (mean total 25(OH)D levels 84.1 ± 23.7 nmol L -1 ; 58 ± 20 nmol L -1 , P = 0.0002; 62.65 ± 19.2 nmol L -1 , P = 0.005; 59.2 ± 21 nmol L -1 , P = 0.005, respectively). Far fewer patients in the overweight and obese groups maintained levels above the recommended level of 75 nmol L -1 52 weeks post-loading (93%; 20%, P = 0.0003; 23%, P = 0.01; and 14%, P = 0.001, respectively). Alternative regimes for the treatment of vitamin D deficiency are needed in overweight and obese patients, especially those in whom bariatric surgery is planned. © 2017 World Obesity Federation.

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

PubMed Central

Nathwani, Amit C.; Tuddenham, Edward G.D.; Rangarajan, Savita; Rosales, Cecilia; McIntosh, Jenny; Linch, David C.; Chowdary, Pratima; Riddell, Anne; Pie, Arnulfo Jaquilmac; Harrington, Chris; O’Beirne, James; Smith, Keith; Pasi, John; Glader, Bertil; Rustagi, Pradip; Ng, Catherine Y.C.; Kay, Mark A.; Zhou, Junfang; Spence, Yunyu; Morton, Christopher L.; Allay, James; Coleman, John; Sleep, Susan; Cunningham, John M.; Srivastava, Deokumar; Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Gray, John T.; Reiss, Ulrike M.; Nienhuis, Arthur W.; Davidoff, Andrew M.

2012-01-01

BACKGROUND Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. METHODS We infused a single dose of a serotype-8–pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. RESULTS AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid–specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. CONCLUSIONS Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.) PMID:22149959

Normal T-cell activation in elite controllers with preserved CD4+ T-cell counts.

PubMed

Bansal, Anju; Sterrett, Sarah; Erdmann, Nathan; Westfall, Andrew O; Dionne-Odom, Jodie; Overton, Edgar T; Goepfert, Paul A

2015-11-01

HIV elite controllers suppress HIV viremia without antiretroviral therapy (ART), yet previous studies demonstrated that elite controllers maintain an activated T-cell phenotype. Chronic immune activation has detrimental consequences and thus ART has been advocated for all elite controllers. However, elite controllers are not a clinically homogenous group. Since CD4% is among the best predictors of AIDS-related events, in the current study, we assessed whether this marker can be used to stratify elite controllers needing ART. Sixteen elite controllers were divided into two groups based on CD4% (EC > 40% and EC ≤40%), and T-cell subsets were analyzed for markers of memory/differentiation (CD45RA, CCR7, CD28), activation (CD38/HLA-DR), immunosenescence (CD57), costimulation (CD73, CD28) and exhaustion (PD-1, CD160, Tim-3). Monocyte subsets (CD14, CD16) were also analyzed and sCD14 levels were quantified using ELISA. In the EC group, expression of activation, exhaustion, and immunosensescence markers on T cells were significantly reduced compared with the EC group and similar to the seronegative controls. The EC group expressed higher levels of costimulatory molecules CD28 and CD73 and had lower levels of monocyte activation (HLA-DR expression) with a reduced frequency of inflammatory monocyte (CD14 CD16) subset. Furthermore, the EC group maintained a stable CD4% during a median follow-up of 6 years. Elite controllers with preserved CD4T cells (EC) have normal T-cell and monocyte phenotypes and therefore may have limited benefit from ART. CD4% can be an important marker for evaluating future studies aimed at determining the need for ART in this group of individuals.

Relationship between PPARα mRNA expression and mitochondrial respiratory function and ultrastructure of the skeletal muscle of patients with COPD.

PubMed

Zhang, Jian-Qing; Long, Xiang-Yu; Xie, Yu; Zhao, Zhi-Huan; Fang, Li-Zhou; Liu, Ling; Fu, Wei-Ping; Shu, Jing-Kui; Wu, Jiang-Hai; Dai, Lu-Ming

2017-11-02

Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.

Abnormal regulation of adenosine 3′,5′-monophosphate and corticosterone formation in an adrenocortical carcinoma

PubMed Central

Ney, R. L.; Hochella, N. J.; Grahame-Smith, D. G.; Dexter, R. N.; Butcher, R. W.

1969-01-01

A spontaneously occurring rat adrenocortical carcinoma which produces corticosterone was maintained by transplantation. The carcinoma appeared to utilize corticosterone biosynthetic steps similar to those of the normal adrenal, but the tumor produced only about 1-10% as much corticosterone per unit tissue weight as nontumorous adrenal glands. The tumor demonstrated little or no increase in corticosterone production in response to adrenocorticotropic hormone (ACTH) either in vivo or in vitro. In normal adrenals, ACTH increases the activity of adenyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine-3′,5′-monophosphate (cyclic AMP), the latter then serving as an intracellular regulator of steroidogenesis. ACTH failed to increase cyclic AMP levels in the tumor in vivo or in slices in vitro, conditions under which there were 50- and 20-fold increases in nontumorous adrenals. However, in homogenates fortified with exogenous ATP, adenyl cyclase activity was comparable in the tumor and adrenals, and cyclic AMP formation was increased 3-fold by ACTH in each. As measured in homogenates, the tumor did not possess a greater ability to destroy cyclic AMP than did normal adrenals. Although ATP levels in the carcinoma were found to be considerably lower than those in normal adrenals, it was not clear that this finding can explain the inability of ACTH to increase cyclic AMP levels in intact tumor cells. While the failure to normally influence cyclic AMP levels in the carcinoma cells could be an important factor in the lack of a steroid response to ACTH, several lines of evidence suggest that the tumor possesses one or more additional abnormalities in the regulation of steroidogenesis. First, in the absence of ACTH stimulation, the tissue concentrations of cyclic AMP were comparable in the tumor and in nontumorous adrenals, but these cyclic AMP levels were associated with a lower level of steroidogenesis in the tumor. Second, tumor slices failed to increase corticosterone production when incubated with cyclic AMP, in contrast to 5-fold increases observed with nontumorous adrenals. PMID:4390412

Anti-diabetic effects of Inonotus obliquus polysaccharides-chromium (III) complex in type 2 diabetic mice and its sub-acute toxicity evaluation in normal mice.

PubMed

Wang, Cong; Chen, Zhongqin; Pan, Yuxiang; Gao, Xudong; Chen, Haixia

2017-10-01

Polysaccharides are important bioactive ingredients from Inonotus obliquus. This study aimed to synthesize and characterize a novel I. obliquus polysaccharides-chromium (III) complex (UIOPC) and investigate the anti-diabetic effects in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) mice and sub-acute toxicity in normal mice. The molecular weight of UIOPC was about 11.5 × 10 4  Da with the chromium content was 13.01% and the chromium was linked with polysaccharides through coordination bond. After treatment of UIOPC for four weeks, the body weight, fasting blood glucose (FBG) levels, plasma insulin levels of the diabetic mice were significantly reduced when compared with those of the diabetic mice (p < 0.05). The results on serum profiles and antioxidant enzymes activities revealed that UIOPC had a positive effect on hypoglycemic and antioxidant ability. Histopathology results showed that UIOPC could effectively alleviate the STZ-lesioned tissues in diabetic mice. Furthermore, high dose administration of UIOPC had no obviously influence on serum profiles levels and antioxidant ability of the normal mice and the organ tissues maintained organized and integrity in the sub-acute toxicity study. These results suggested that UIOPC might be a good candidate for the functional food or pharmaceuticals in the treatment of T2DM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parathyroid hormone gene expression in hypophosphatemic rats.

PubMed Central

Kilav, R; Silver, J; Naveh-Many, T

1995-01-01

Phosphate is central to bone metabolism and we have therefore studied whether parathyroid hormone (PTH) is regulated by dietary phosphate in vivo. Weanling rats were fed diets with different phosphate contents for 3 wk: low phosphate (0.02%), normal calcium (0.6%), normal phosphate (0.3%), and calcium (0.6%); high phosphate (1.2%), high calcium (1.2%). The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)2D3 together with decreased PTH mRNA levels (25 +/- 8% of controls, P < 0.01) and serum immunoreactive PTH (4.7 +/- 0.8: 22.1 +/- 3.7 pg/ml; low phosphate: control, P < 0.05). A high phosphate diet led to increased PTH mRNA levels. In situ hybridization showed that hypophosphatemia decreased PTH mRNA in all the parathyroid cells. To separate the effect of low phosphate from changes in calcium and vitamin D rats were fed diets to maintain them as vitamin D-deficient and normocalcemic despite the hypophosphatemia. Hypophosphatemic, normocalemic rats with normal serum 1,25(OH)2D3 levels still had decreased PTH mRNAs. Nuclear transcript run-ons showed that the effect of low phosphate was posttranscriptional. Calcium and 1,25(OH)2D3 regulate the parathyroid and we now show that dietary phosphate also regulates the parathyroid by a mechanism which remains to be defined. Images PMID:7615802

Systemic production of IFN-alpha by garlic (Allium sativum) in humans.

PubMed

Bhattacharyya, Mau; Girish, G V; Karmohapatra, Soumendra K; Samad, S A; Sinha, Asru K

2007-05-01

The effect of foods on the production of interferon-alpha (IFN-alpha) is currently unknown. Garlic (Allium sativum) used as a folk medicine is reported to stimulate nitric oxide (NO) production. We investigated the systemic increase of NO due to the ingestion of garlic on the plasma IFN-alpha level in normal volunteers. Normal volunteers (10 groups, 10 in each group) ate 2 g fresh garlic, and plasma NO and IFN-alpha levels were determined after 2 and 4 h. The participants were also asked to eat garlic for various periods of time, and plasma NO and IFN-alpha were similarly assayed. Ingestion of 2 g fresh, but not boiled, garlic was found to increase the basal plasma level of NO from 2.7 +/- 0.1 microM to 8.76 +/- 0.21 microM at 2 and 4 h, respectively. The basal plasma IFN-alpha level increased from 9.51 +/- 0.26 nM to 46.3 +/- 1.2 nM in normal volunteers (n = 10) at the same time. The chronic eating of garlic was found to maintain IFN-alpha at high levels for at least 7 days. The exposure of neutrophils to garlic in vivo or in vitro, which also stimulated synthesis of NO in these cells, was found to stimulate IFN-alpha synthesis as measured by the stimulation of IFN-alpha mRNA synthesis. Thus, consumption of garlic resulted in stimulated synthesis of NO and, in turn, IFN-alpha in humans, which could be beneficial in viral or proliferative diseases.

Neuroimaging markers associated with maintenance of optimal memory performance in late-life.

PubMed

Dekhtyar, Maria; Papp, Kathryn V; Buckley, Rachel; Jacobs, Heidi I L; Schultz, Aaron P; Johnson, Keith A; Sperling, Reisa A; Rentz, Dorene M

2017-06-01

Age-related memory decline has been well-documented; however, some individuals reach their 8th-10th decade while maintaining strong memory performance. To determine which demographic and biomarker factors differentiated top memory performers (aged 75+, top 20% for memory) from their peers and whether top memory performance was maintained over 3 years. Clinically normal adults (n=125, CDR=0; age: 79.5±3.57 years) from the Harvard Aging Brain Study underwent cognitive testing and neuroimaging (amyloid PET, MRI) at baseline and 3-year follow-up. Participants were grouped into Optimal (n=25) vs. Typical (n=100) performers using performance on 3 challenging memory measures. Non-parametric tests were used to compare groups. There were no differences in age, sex, or education between Optimal vs. Typical performers. The Optimal group performed better in Processing Speed (p=0.016) and Executive Functioning (p<0.001). Optimal performers had larger hippocampal volumes at baseline compared with Typical Performers (p=0.027) but no differences in amyloid burden (p=0.442). Twenty-three of the 25 Optimal performers had longitudinal data and16 maintained top memory performance while 7 declined. Non-Maintainers additionally declined in Executive Functioning but not Processing Speed. Longitudinally, there were no hippocampal volume differences between Maintainers and Non-Maintainers, however Non-Maintainers exhibited higher amyloid burden at baseline in contrast with Maintainers (p=0.008). Excellent memory performance in late life does not guarantee protection against cognitive decline. Those who maintain an optimal memory into the 8th and 9th decades may have lower levels of AD pathology. Copyright © 2017. Published by Elsevier Ltd.

Eliminating animal facility light-at-night contamination and its effect on circadian regulation of rodent physiology, tumor growth, and metabolism: a challenge in the relocation of a cancer research laboratory.

PubMed

Dauchy, Robert T; Dupepe, Lynell M; Ooms, Tara G; Dauchy, Erin M; Hill, Cody R; Mao, Lulu; Belancio, Victoria P; Slakey, Lauren M; Hill, Steven M; Blask, David E

2011-05-01

Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR(-)) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O(2), glucose, total fatty acid and CO(2) production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine-threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen.

Eliminating Animal Facility Light-at-Night Contamination and Its Effect on Circadian Regulation of Rodent Physiology, Tumor Growth, and Metabolism: A Challenge in the Relocation of a Cancer Research Laboratory

PubMed Central

Dauchy, Robert T; Dupepe, Lynell M; Ooms, Tara G; Dauchy, Erin M; Hill, Cody R; Mao, Lulu; Belancio, Victoria P; Slakey, Lauren M; Hill, Steven M; Blask, David E

2011-01-01

Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR–) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O2, glucose, total fatty acid and CO2 production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine–threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen. PMID:21640027

[Relationship between breast milk composition and weight growth velocity of infants fed with exclusive breast milk].

PubMed

Huang, Li-Li; Xiong, Fei; Yang, Fan

2016-10-01

To study the effect of breast milk composition on weight growth velocity of infants fed with exclusive breast milk. One hundred and thirty-eight full-term singleton infants who received regular follow-up visits and fed with exclusive breast milk and their mothers were recruited. Body height, weight and head circumference of these infants were measured at regular visits. Z scores were used to evaluate growth velocity. The subjects were classified into a failure to thrive group (ΔZ scores≤-0.67), a poor growth group (-0.67<ΔZ scores<0) and a normal control group (ΔZ scores≥0). The samples of mature breast milk were collected for composition analysis. The differences in the levels of the protein, fats, energy, carbohydrates and minerals in breast milk were compared among the three groups. ΔZ scores for weight in the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). There was no significant difference in the levels of protein, fats and energy in breast milk among the failure to thrive, poor growth and normal control groups. However, the levels of carbohydrates and minerals in both the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). Weight growth velocity of infants can be affected by the composition of breast milk to a certain degree in a short period. In order to maintain a good weight growth velocity of infants, mothers should have a balanced diet to improve the quality of breast milk.

Necessity of the glossopharyngeal nerve in the maintenance of normal intake and ingestive bout size of corn oil by rats.

PubMed

Treesukosol, Yada; Blonde, Ginger D; Jiang, Enshe; Gonzalez, Dani; Smith, James C; Spector, Alan C

2010-10-01

Recent evidence in the literature suggests that signals carried by the glossopharyngeal nerve (GL), which supplies sensory and parasympathetic innervation of the posterior tongue, might be essential in the maintenance of normal gustatory responses to fat stimuli. Here, we report that GL transection (GLX) significantly decreased corn oil intake and preference in 23-h two-bottle tests relative to sham-operated controls (Sham). Drinking-pattern analysis of corn oil licking revealed that bout size, rather than the number of bouts initiated, was smaller in GLX than Sham rats. We also tested a range of glucose concentrations and found that total licks over daily 23-h sessions significantly decreased in GLX compared with Sham rats, but this difference failed to reach significance when intake or any bout parameter was measured. These results show that the signals in the GL normally contribute to processes involved with corn oil bout termination as opposed to bout initiation. GL-derived signals could potentially provide input to "reward" circuits in the ventral forebrain that could serve to maintain ingestion during a meal or, alternatively, could act at the level of the brain stem to attenuate the inhibitory potency of vagal signals, thus delaying the onset of satiation, or perhaps contribute to a cephalic phase reflex modulation of the gut. Parasympathetic efferents in the GL innervating the von Ebner's glands, which secrete lingual lipase, which is thought to break down corn oil into detectable ligands, could also be playing a role in driving corn oil intake. Whatever the mechanism, an intact GL is clearly necessary in maintaining normal intake of corn oil.

[Effect of stress on nucleic acid metabolism in the rat spleen and liver after a flight on the Kosmos-1129 biosatellite].

PubMed

Komolova, G S; Troitskaia, E N; Egorov, I A; Tigranian, R A

1982-01-01

Changes in nucleic acid metabolism of the spleen and liver of rats flown for 18.5 days on Cosmos-112 were investigated. Postflight changes in the liver RNA synthesis after an additional stress effect (immobilization) in the flown rats were expressed to a lesser degree than in the controls. The DNA synthesis remained essentially at the preflight level. The tissue content of nucleic acids suggests that postflight the dystrophic changes induced by the additional stress effect increased. It is very likely that an exposure to space flight effects contributes to the depletion of compensatory mechanisms maintaining the normal level of metabolic processes.

A Simple and Effective Image Normalization Method to Monitor Boreal Forest Change in a Siberian Burn Chronosequence across Sensors and across Time

NASA Astrophysics Data System (ADS)

Chen, X.; Vierling, L. A.; Deering, D. W.

2004-12-01

Satellite data offer unique perspectives for monitoring and quantifying land cover change, however, the radiometric consistency among co-located multi-temporal images is difficult to maintain due to variations in sensors and atmosphere. To detect accurate landscape change using multi-temporal images, we developed a new relative radiometric normalization scheme: the temporally invariant cluster (TIC) method. Image data were acquired on 9 June 1990 (Landsat 4), 20 June 2000, and 26 August 2001 (Landsat 7) for analyses over boreal forests near the Siberian city of Krasnoyarsk. Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), and Reduced Simple Ratio (RSR) were investigated in the normalization study. The temporally invariant cluster (TIC) centers were identified through a point density map of the base image and the target image and a normalization regression line was created through all TIC centers. The target image digital data were then converted using the regression function so that the two images could be compared using the resulting common radiometric scale. We found that EVI was very sensitive to vegetation structure and could thus be used to separate conifer forests from deciduous forests and grass/crop lands. NDVI was a very effective vegetation index to reduce the influence of shadow, while EVI was very sensitive to shadowing. After normalization, correlations of NDVI and EVI with field collected total Leaf Area Index (LAI) data in 2000 and 2001 were significantly improved; the r-square values in these regressions increased from 0.49 to 0.69 and from 0.46 to 0.61, respectively. An EVI ¡°cancellation effect¡± where EVI was positively related to understory greenness but negatively related to forest canopy coverage was evident across a post fire chronosequence. These findings indicate that the TIC method provides a simple, effective and repeatable method to create radiometrically comparable data sets for remote detection of landscape change. Compared with some previous relative normalization methods, this new method can avoid subjective selection of a normalization regression line. It does not require high level programming and statistical analyses, yet remains sensitive to landscape changes occurring over seasonal and inter-annual time scales. In addition, the TIC method maintains sensitivity to subtle changes in vegetation phenology and enables normalization even when invariant features are rare.

Plasma hormonal and electrolyte alterations in cycling buffaloes ( Bubalus bubalis) during hot summer months

NASA Astrophysics Data System (ADS)

Singh, Narinder; Chaudhary, K. C.

1992-09-01

Plasma levels of progesterone, prolactin, luteinizing hormone, and electrolytes were monitored by radioimmunoassay in ten cycling buffaloes maintained at Punjab Agricultural University, Ludhiana during the hot summer months of June July. The plasma progesterone concentration ranged from 0.28±0.04 to 3.09±0.03 ng/ml at various stages of the oestrous cycle. Prolactin values ranged from 319±23 to 371±25 ng/ml and LH levels from 0.95±0.05 to 1.35±0.08 ng/ml. Concentrations differed significantly ( P⩽0.05) at various stages of the cycle. Levels of electrolytes, viz. Ca+ +, Na+ and K+, were well within the normal range. The high levels of prolactin, progesterone and LH during the hot summer were assessed in relation to poor reproductive efficiency in buffaloes.

Extraction of quasi-straightforward-propagating photons from diffused light transmitting through a scattering medium by polarization modulation

NASA Astrophysics Data System (ADS)

Horinaka, Hiromichi; Hashimoto, Koji; Wada, Kenji; Cho, Yoshio; Osawa, Masahiko

1995-07-01

The utilization of light polarization is proposed to extract quasi-straightforward-propagating photons from diffused light transmitting through a scattering medium under continuously operating conditions. Removal of a floor level normally appearing on the dynamic range over which the extraction capability is maintained is demonstrated. By use of pulse-based observations this cw scheme of extraction of quasi-straightforward-propagating photons is directly shown to be equivalent to the use of a temporal gate in the pulse-based operation.

Evaluation of structural issues related to isolation of the 100-KE/100-KW discharge chute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winkel, B.V.; Hyde, L.L.

The issue of excessive post-seismic leakage in the discharge chute of the K East and K West fuel storage basins was resolved by designing isolation barriers to maintain basin water levels if the discharge chute should drain. This report addresses the structural issues associated with isolation of the discharge chute. The report demonstrates the structural adequacy of the components associated with chute isolation for normal and seismic loading. Associated issues, such as hardware drop accidents and seismic slosh heights are also addressed.

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2014 CFR

2014-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2013 CFR

2013-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2010 CFR

2010-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2012 CFR

2012-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2011 CFR

2011-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

Normal postprandial nonesterified fatty acid uptake in muscles despite increased circulating fatty acids in type 2 diabetes.

PubMed

Labbé, Sébastien M; Croteau, Etienne; Grenier-Larouche, Thomas; Frisch, Frédérique; Ouellet, René; Langlois, Réjean; Guérin, Brigitte; Turcotte, Eric E; Carpentier, André C

2011-02-01

Postprandial plasma nonesterified fatty acid (NEFA) appearance is increased in type 2 diabetes. Our objective was to determine whether skeletal muscle uptake of plasma NEFA is abnormal during the postprandial state in type 2 diabetes. Thigh muscle blood flow and oxidative metabolism indexes and NEFA uptake were determined using positron emission tomography coupled with computed tomography (PET/CT) with [(11)C]acetate and 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)FTHA) in seven healthy control subjects (CON) and seven subjects with type 2 diabetes during continuous oral intake of a liquid meal to achieve steady postprandial NEFA levels with insulin infusion to maintain similar plasma glucose levels in both groups. In the postprandial state, plasma NEFA level was higher in type 2 diabetic subjects versus CON (P < 0.01), whereas plasma glucose was at the same level in both groups. Muscle NEFA fractional extraction and blood flow index levels were 56% (P < 0.05) and 24% (P = 0.27) lower in type 2 diabetes, respectively. However, muscle NEFA uptake was similar to that of CON (quadriceps femoris [QF] 1.47 ± 0.23 vs. 1.37 ± 0.24 nmol·g(-1)·min(-1), P = 0.77; biceps femoris [BF] 1.54 ± 0.26 vs. 1.46 ± 0.28 nmol·g(-1)·min(-1), P = 0.85). Muscle oxidative metabolism was similar in both groups. Muscle NEFA fractional extraction and blood flow index were strongly and positively correlated (r = 0.79, P < 0.005). Postprandial muscle NEFA uptake is normal despite elevated systemic NEFA levels and acute normalization of plasma glucose in type 2 diabetes. Lower postprandial muscle blood flow with resulting reduction in muscle NEFA fractional extraction may explain this phenomenon.

Supporting adolescents with type 1 diabetes mellitus: a qualitative study.

PubMed

Rostami, Shahnaz; Parsa-Yekta, Zohreh; Najafi Ghezeljeh, Tahereh; Vanaki, Zohreh

2014-03-01

Without sufficient support, type 1 diabetes mellitus often disturbs patients' normal lives. This study describes and explores the support that Iranian adolescents with type 1 diabetes mellitus experienced. Semistructured interviews were conducted with ten adolescents, seven family members, one dietitian, one nurse, and one school nurse. Participants were chosen using purposive sampling from two teaching hospitals and one high school in two urban areas of Iran. Using standard procedures for content analysis, three main themes were identified: maintaining a normal life; receiving tangible, informational, and emotional support from the family and society; and advancement of life toward normalization. The cornerstone of maintaining a normal life for adolescents with type 1 diabetes mellitus is to adopt an active role in taking care of themselves within their systems of support. © 2013 Wiley Publishing Asia Pty Ltd.

Vitamin A status of Filipino preschool children given a massive oral dose.

PubMed

Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I

1996-12-01

The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (< 20 microg/dl) levels were significantly lower one and six months after supplementation. All follow-up serum retinol levels of children with deficient and low values at baseline were significantly lower (p < 0.001) than those with normal values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

Is supplementation efficacious in maintaining adequate plasma levels of vitamin a and e for thalassemic patients undergoing hematopoietic stem cell transplantation? A cross-sectional study.

PubMed

Hajimahmoodi, Mannan; Hadjibabaie, Molouk; Hamidieh, Amir-Ali; Ahmadvand, Alireza; Kazempanah, Sahebeh; Sadeghi, Naficeh; Mansouri, Ava; Ghavamzadeh, Ardeshir

2014-02-01

Thalassemia along with hematopoietic stem cell transplantation (HSCT) can lead to major oxidative stress. Vitamins A and E are antioxidants which protect membrane from lipid peroxidation. We sought to determine for the first time, whether vitamins A and E supplementation is efficacious in maintaining or increasing plasma level of these vitamins in thalassemic children undergoing HSCT. A cross-sectional study was performed on 50 children with β-thalassemia major hospitalized for HSCT. Patients took a daily multivitamin. Plasma vitamins A and E levels were measured at four different times: on admission, HSCT day (day 0), day 7 and day 14 after HSCT. Findings : Plasma vitamin A and E were abnormal on admission in most patients (62.0% and 60.0% respectively). Ratio of patient with normal to abnormal plasma level of the vitamins improved from baseline to a peak on day 7 then deteriorated afterward until day 14. There was an increasingly positive correlation between daily oral intake and plasma vitamin A at different times, but plasma vitamin E showed inverse correlation at first which tended towards no correlation subsequently. In multivariate analysis, supplementation significantly changed plasma level of vitamin A at different measurement time (P=0.001) within study subjects. But, plasma level of vitamin E showed no significant difference (P=0.2). Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion.

Candidate Reference Genes Selection and Application for RT-qPCR Analysis in Kenaf with Cytoplasmic Male Sterility Background

PubMed Central

Zhou, Bujin; Chen, Peng; Khan, Aziz; Zhao, Yanhong; Chen, Lihong; Liu, Dongmei; Liao, Xiaofang; Kong, Xiangjun; Zhou, Ruiyang

2017-01-01

Cytoplasmic male sterility (CMS) is a maternally inherited trait that results in the production of dysfunctional pollen. Based on reliable reference gene-normalized real-time quantitative PCR (RT-qPCR) data, examining gene expression profile can provide valuable information on the molecular mechanism of kenaf CMS. However, studies have not been conducted regarding selection of reference genes for normalizing RT-qPCR data in the CMS and maintainer lines of kenaf crop. Therefore, we studied 10 candidate reference genes (ACT3, ELF1A, G6PD, PEPKR1, TUB, TUA, CYP, GAPDH, H3, and 18S) to assess their expression stability at three stages of pollen development in CMS line 722A and maintainer line 722B of kenaf. Five computational statistical approaches (GeNorm, NormFinder, ΔCt, BestKeeper, and RefFinder) were used to evaluate the expression stability levels of these genes. According to RefFinder and GeNorm, the combination of TUB, CYP, and PEPKR1 was identified as an internal control for the accurate normalization across all sample set, which was further confirmed by validating the expression of HcPDIL5-2a. Furthermore, the combination of TUB, CYP, and PEPKR1 was used to differentiate the expression pattern of five mitochondria F1F0-ATPase subunit genes (atp1, atp4, atp6, atp8, and atp9) by RT-qPCR during pollen development in CMS line 722A and maintainer line 722B. We found that atp1, atp6, and atp9 exhibited significantly different expression patterns during pollen development in line 722A compared with line 722B. This is the first systematic study of reference genes selection for CMS and will provide useful information for future research on the gene expressions and molecular mechanisms underlying CMS in kenaf. PMID:28919905

Adaptive track scheduling to optimize concurrency and vectorization in GeantV

DOE PAGES

Apostolakis, J.; Bandieramonte, M.; Bitzes, G.; ...

2015-05-22

The GeantV project is focused on the R&D of new particle transport techniques to maximize parallelism on multiple levels, profiting from the use of both SIMD instructions and co-processors for the CPU-intensive calculations specific to this type of applications. In our approach, vectors of tracks belonging to multiple events and matching different locality criteria must be gathered and dispatched to algorithms having vector signatures. While the transport propagates tracks and changes their individual states, data locality becomes harder to maintain. The scheduling policy has to be changed to maintain efficient vectors while keeping an optimal level of concurrency. The modelmore » has complex dynamics requiring tuning the thresholds to switch between the normal regime and special modes, i.e. prioritizing events to allow flushing memory, adding new events in the transport pipeline to boost locality, dynamically adjusting the particle vector size or switching between vector to single track mode when vectorization causes only overhead. Lastly, this work requires a comprehensive study for optimizing these parameters to make the behaviour of the scheduler self-adapting, presenting here its initial results.« less

Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis.

PubMed

Matsumoto, Kotaro; Ichimura, Mayuko; Tsuneyama, Koichi; Moritoki, Yuki; Tsunashima, Hiromichi; Omagari, Katsuhisa; Hara, Masumi; Yasuda, Ichiro; Miyakawa, Hiroshi; Kikuchi, Kentaro

2017-01-01

Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet. Fecal bacteria, short-chain fatty acids, and immunoglobulin A (IgA) levels were investigated. Histological and immunohistochemical examinations were performed using mice livers for CD14 and Toll-like receptor-4 (TLR4) expression and intestinal tissue samples for IgA and zonula occludens-1 expression in epithelial tight junctions. The methionine-choline-deficient mice administered 5% fructo-oligosaccharides maintained a normal gastrointestinal microbiome, whereas methionine-choline-deficient mice without prebiotic supplementation displayed increases in Clostridium cluster XI and subcluster XIVa populations and a reduction in Lactobacillales spp. counts. Methionine-choline-deficient mice given 5% fructo-oligosaccharides exhibited significantly decreased hepatic steatosis (p = 0.003), decreased liver inflammation (p = 0.005), a decreased proportion of CD14-positive Kupffer cells (p = 0.01), decreased expression of TLR4 (p = 0.04), and increases in fecal short-chain fatty acid and IgA concentrations (p < 0.04) compared with the findings in methionine-choline-deficient mice that were not administered this prebiotic. This study illustrated that in the methionine-choline-deficient mouse model, dietary fructo-oligosaccharides can restore normal gastrointestinal microflora and normal intestinal epithelial barrier function, and decrease steatohepatitis. The findings support the role of prebiotics, such as fructo-oligosaccharides, in maintaining a normal gastrointestinal microbiome; they also support the need for further studies on preventing or treating nonalcoholic steatohepatitis using dietary fructo-oligosaccharides.

The role of auditory and kinaesthetic feedback mechanisms on phonatory stability in children.

PubMed

Rathna Kumar, S B; Azeem, Suhail; Choudhary, Abhishek Kumar; Prakash, S G R

2013-12-01

Auditory feedback plays an important role in phonatory control. When auditory feedback is disrupted, various changes are observed in vocal motor control. Vocal intensity and fundamental frequency (F0) levels tend to increase in response to auditory masking. Because of the close reflexive links between the auditory and phonatory systems, it is likely that phonatory stability may be disrupted when auditory feedback is disrupted or altered. However, studies on phonatory stability under auditory masking condition in adult subjects showed that most of the subjects maintained normal levels of phonatory stability. The authors in the earlier investigations suggested that auditory feedback is not the sole contributor to vocal motor control and phonatory stability, a complex neuromuscular reflex system known as kinaesthetic feedback may play a role in controlling phonatory stability when auditory feedback is disrupted or lacking. This proposes the need to further investigate this phenomenon as to whether children show similar patterns of phonatory stability under auditory masking since their neuromotor systems are still at developmental stage, less mature and are less resistant to altered auditory feedback than adults. A total of 40 normal hearing and speaking children (20 male and 20 female) between the age group of 6 and 8 years participated as subjects. The acoustic parameters such as shimmer, jitter and harmonic-to-noise ratio (HNR) were measures and compared between no masking condition (0 dB ML) and masking condition (90 dB ML). Despite the neuromotor systems being less mature in children and less resistant than adults to altered auditory feedback, most of the children in the study demonstrated increased phonatory stability which was reflected by reduced shimmer, jitter and increased HNR values. This study implicates that most of the children demonstrate well established patterns of kinaesthetic feedback, which might have allowed them to maintain normal levels of vocal motor control even in the presence of disturbed auditory feedback. Hence, it can be concluded that children also exhibit kinaesthetic feedback mechanism to control phonatory stability when auditory feedback is disrupted which in turn highlights the importance of kinaesthetic feedback to be included in the therapeutic/intervention approaches for children with hearing and neurogenic speech deficits.

Cardiovascular effects of anti-G suit inflation at 1 and 2 G.

PubMed

Montmerle, Stéphanie; Linnarsson, Dag

2005-06-01

We sought to determine to which pressure a full-coverage anti-G suit needs to be inflated in order to obtain the same stroke volume during a brief exposure to twice the normal gravity (2 G) as that at 1 G without anti-G suit inflation. Nine sitting subjects were studied at normal (1 G) and during 20 s of exposure to 2 G. They wore anti-G suits, which were inflated at both G-levels to the following target pressures: 0, 70, 140 and 210 mmHg. Stroke volume was computed from cardiac output, which was measured by rebreathing. Heart rate and mean arterial pressure at heart level were recorded. Inflation to 70 mmHg compensated for the decrease in stroke volume and cardiac output caused by hypergravity. Mean arterial pressure at heart level was comparable at 1 G and at 2 G and increased gradually and similarly with inflation (P<0.001) at both gravity levels. Thus, anti-G suits act by increasing both preload and afterload but the two effects counteract each other in terms of cardiac output, so that cardiac output at 2 G is maintained at its 1 G level. This effect is reached already at 70 mmHg of inflation. Greater inflation pressure further increases mean arterial pressure at heart level and compensates for the increased difference in hydrostatic pressure between heart and head in moderate hypergravity.

Unique spatial and cellular expression patterns of Hoxa5, Hoxb4 and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia

PubMed Central

Volpe, MaryAnn Vitoria; Wang, Karen Ting Wai; Nielsen, Heber Carl; Chinoy, Mala Romeshchandra

2009-01-01

Background Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 proteins compared to normal lung development. Methods Temporal, spatial and cellular Hoxa5, Hoxb4 and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, 19 fetuses and neonates using western blot and immunohistochemistry. Results Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 isoforms changed with development and further in NT-PH lungs. Compared to normal lungs, Gd19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways. Conclusions Unique spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition. PMID:18553509

Stem cells and corneal epithelial maintenance – insights from the mouse and other animal models

PubMed Central

Mort, Richard L.; Douvaras, Panagiotis; Morley, Steven D.; Dorà, Natalie; Hill, Robert E.; Collinson, J. Martin; West, John D.

2012-01-01

Maintenance of the corneal epithelium is essential for vision and is a dynamic process incorporating constant cell production, movement and loss. Although cell based therapies involving the transplantation of putative stem cells are well advanced for the treatment of human corneal defects, the scientific understanding of these interventions is poor. No definitive marker that discriminates stem cells that maintain the corneal epithelium from the surrounding tissue has been discovered and the identity of these elusive cells is, therefore, hotly debated. The key elements of corneal epithelial maintenance have long been recognised but it is still not known how this dynamic balance is coordinated during normal homeostasis to ensure the corneal epithelium is maintained at a uniform thickness. Most indirect experimental evidence supports the limbal epithelial stem cell (LESC) hypothesis, which proposes that the adult corneal epithelium is maintained by stem cells located in the limbus at the corneal periphery. However, this has been challenged recently by the corneal epithelial stem cell (CESC) hypothesis, which proposes that during normal homeostasis the mouse corneal epithelium is maintained by stem cells located throughout the basal corneal epithelium with LESCs only contributing during wound healing. In this chapter we review experimental studies, mostly based on animal work, that provide insights into how stem cells maintain the normal corneal epithelium and consider the merits of the alternative LESC and CESC hypotheses. Finally, we highlight some recent research on other stem cell systems and consider how this could influence future research directions for identifying the stem cells that maintain the corneal epithelium. PMID:22918816

Application of extremum seeking for time-varying systems to resonance control of RF cavities

DOE PAGES

Scheinker, Alexander

2016-09-13

A recently developed form of extremum seeking for time-varying systems is implemented in hardware for the resonance control of radio-frequency cavities without phase measurements. Normal conducting RF cavity resonance control is performed via a slug tuner, while superconducting TESLA-type cavity resonance control is performed via piezo actuators. The controller maintains resonance by minimizing reflected power by utilizing model-independent adaptive feedback. Unlike standard phase-measurement-based resonance control, the presented approach is not sensitive to arbitrary phase shifts of the RF signals due to temperature-dependent cable length or phasemeasurement hardware changes. The phase independence of this method removes common slowly varying drifts andmore » required periodic recalibration of phase-based methods. A general overview of the adaptive controller is presented along with the proof of principle experimental results at room temperature. Lastly, this method allows us to both maintain a cavity at a desired resonance frequency and also to dynamically modify its resonance frequency to track the unknown time-varying frequency of an RF source, thereby maintaining maximal cavity field strength, based only on power-level measurements.« less

Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy

NASA Technical Reports Server (NTRS)

Headley, J. A.; Theriault, R. L.; LeBlanc, A. D.; Vassilopoulou-Sellin, R.; Hortobagyi, G. N.

1998-01-01

The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheinker, Alexander

A recently developed form of extremum seeking for time-varying systems is implemented in hardware for the resonance control of radio-frequency cavities without phase measurements. Normal conducting RF cavity resonance control is performed via a slug tuner, while superconducting TESLA-type cavity resonance control is performed via piezo actuators. The controller maintains resonance by minimizing reflected power by utilizing model-independent adaptive feedback. Unlike standard phase-measurement-based resonance control, the presented approach is not sensitive to arbitrary phase shifts of the RF signals due to temperature-dependent cable length or phasemeasurement hardware changes. The phase independence of this method removes common slowly varying drifts andmore » required periodic recalibration of phase-based methods. A general overview of the adaptive controller is presented along with the proof of principle experimental results at room temperature. Lastly, this method allows us to both maintain a cavity at a desired resonance frequency and also to dynamically modify its resonance frequency to track the unknown time-varying frequency of an RF source, thereby maintaining maximal cavity field strength, based only on power-level measurements.« less

Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development.

PubMed

Amory, J K; Anawalt, B D; Bremner, W J; Matsumoto, A M

2001-01-01

Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences in serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins explain why some men fail to completely suppress their sperm counts to zero with weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain persistent spermatogenesis in some men treated with androgen-based contraceptive regimens.

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

PubMed

Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D

1971-03-01

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

Precision contact of the fingertip reduces postural sway of individuals with bilateral vestibular loss

NASA Technical Reports Server (NTRS)

Lackner, J. R.; DiZio, P.; Jeka, J.; Horak, F.; Krebs, D.; Rabin, E.

1999-01-01

Contact of the hand with a stationary surface attenuates postural sway in normal individuals even when the level of force applied is mechanically inadequate to dampen body motion. We studied whether subjects without vestibular function would be able to substitute contact cues from the hand for their lost labyrinthine function and be able to balance as well as normal subjects in the dark without finger contact. We also studied the relative contribution of sight of the test chamber to the two groups. Subjects attempted to maintain a tandem Romberg stance for 25 s under three levels of fingertip contact: no contact; light-touch contact, up to 1 N (approximately 100 g) force; and unrestricted contact force. Both eyes open and eyes closed conditions were evaluated. Without contact, none of the vestibular loss subjects could stand for more than a few seconds in the dark without falling; all the normals could. The vestibular loss subjects were significantly more stable in the dark with light touch of the index finger than the normal subjects in the dark without touch. They also swayed less in the dark with light touch than when permitted sight of the test chamber without touch, and less with sight and touch than just sight. The normal subjects swayed less in the dark with touch than without, and less with sight and touch than sight alone. These findings show that during quiet stance light touch of the index finger with a stationary surface can be as effective or even more so than vestibular function for minimizing postural sway.

Moisturizers: Options for Softer Skin

MedlinePlus

... you have specific conditions, such as acne. For general guidelines, consider the following Normal skin. Normal skin is neither too dry nor too oily. To maintain this natural moisture balance, use a water-based moisturizer that has a ...

10 CFR 72.236 - Specific requirements for spent fuel storage cask approval and fabrication.

Code of Federal Regulations, 2013 CFR

2013-01-01

... maintained in a subcritical condition under credible conditions. (d) Radiation shielding and confinement... confinement of radioactive material under normal, off-normal, and credible accident conditions. (m) To the...

10 CFR 72.236 - Specific requirements for spent fuel storage cask approval and fabrication.

Code of Federal Regulations, 2012 CFR

2012-01-01

... maintained in a subcritical condition under credible conditions. (d) Radiation shielding and confinement... confinement of radioactive material under normal, off-normal, and credible accident conditions. (m) To the...

10 CFR 72.236 - Specific requirements for spent fuel storage cask approval and fabrication.

Code of Federal Regulations, 2010 CFR

2010-01-01

... maintained in a subcritical condition under credible conditions. (d) Radiation shielding and confinement... of radioactive material under normal, off-normal, and credible accident conditions. (m) To the extent...

10 CFR 72.236 - Specific requirements for spent fuel storage cask approval and fabrication.

Code of Federal Regulations, 2011 CFR

2011-01-01

... maintained in a subcritical condition under credible conditions. (d) Radiation shielding and confinement... of radioactive material under normal, off-normal, and credible accident conditions. (m) To the extent...

10 CFR 72.236 - Specific requirements for spent fuel storage cask approval and fabrication.

Code of Federal Regulations, 2014 CFR

2014-01-01

... maintained in a subcritical condition under credible conditions. (d) Radiation shielding and confinement... confinement of radioactive material under normal, off-normal, and credible accident conditions. (m) To the...

Sertoli cell androgen receptor expression regulates temporal fetal and adult Leydig cell differentiation, function, and population size.

PubMed

Hazra, Rasmani; Jimenez, Mark; Desai, Reena; Handelsman, David J; Allan, Charles M

2013-09-01

We recently created a mouse model displaying precocious Sertoli cell (SC) and spermatogenic development induced by SC-specific transgenic androgen receptor expression (TgSCAR). Here we reveal that TgSCAR regulates the development, function, and absolute number of Leydig cells (LCs). Total fetal and adult type LC numbers were reduced in postnatal and adult TgSCAR vs control testes, despite normal circulating LH levels. Normal LC to SC ratios found in TgSCAR testes indicate that SC androgen receptor (SCAR)-mediated activity confers a quorum-dependent relationship between total SC and LC numbers. TgSCAR enhanced LC differentiation, shown by elevated ratios of advanced to immature LC types, and reduced LC proliferation in postnatal TgSCAR vs control testes. Postnatal TgSCAR testes displayed up-regulated expression of coupled ligand-receptor transcripts (Amh-Amhr2, Dhh-Ptch1, Pdgfa-Pdgfra) for potential SCAR-stimulated paracrine pathways, which may coordinate LC differentiation. Neonatal TgSCAR testes displayed normal T and dihydrotestosterone levels despite differential changes to steroidogenic gene expression, with down-regulated Star, Cyp11a1, and Cyp17a1 expression contrasting with up-regulated Hsd3b1, Hsd17b3, and Srd5a1 expression. TgSCAR males also displayed elevated postnatal and normal adult serum testosterone levels, despite reduced LC numbers. Enhanced adult-type LC steroidogenic output was revealed by increased pubertal testicular T, dihydrotestosterone, 3α-diol and 3β-diol levels per LC and up-regulated steroidogenic gene (Nr5a1, Lhr, Cyp11a1, Cyp17a1, Hsd3b6, Srd5a1) expression in pubertal or adult TgSCAR vs control males, suggesting regulatory mechanisms maintain androgen levels independently of absolute LC numbers. Our unique gain-of-function TgSCAR model has revealed that SCAR activity controls temporal LC differentiation, steroidogenic function, and population size.

The epidermal growth factor receptor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract.

PubMed Central

Playford, R J; Hanby, A M; Gschmeissner, S; Peiffer, L P; Wright, N A; McGarrity, T

1996-01-01

BACKGROUND: While it is clear that luminal epidermal growth factor (EGF) stimulates repair of the damaged bowel, its significance in maintaining normal gut growth remains uncertain. If EGF is important in maintaining normal gut growth, the EGF receptor (EGF-R) should be present on the apical (luminal) surface in addition to the basolateral surface. AIMS/SUBJECTS/METHODS: This study examined the distribution of the EGF-R in the epithelium throughout the human gastro-intestinal tract using immunohistochemistry, electron microscopy, and western blotting of brush border preparations. RESULTS: Immunostaining of the oesophagus showed circumferential EGF-R positivity in the cells of the basal portions of the stratified squamous epithelium but surface cells were EGF-R negative. In the normal stomach, small intestine, and colon, immunostaining localised the receptor to the basolateral surface with the apical membranes being consistently negative. EGF-R positivity within the small intestine appeared to be almost entirely restricted to the proliferative (crypt) region. Western blotting demonstrated a 170 kDa protein in whole tissue homogenates but not in the brush border vesicle preparations. CONCLUSIONS: As the EGF-R is located only on the basolateral surfaces in the normal adult gastrointestinal tract, the major role of luminal EGF is probably to stimulate repair rather than to maintain normal gut growth. Images Figure 1 Figure 2 Figure 3 PMID:8977341

Assessment of sperm DNA in patients submitted the assisted reproduction technology procedures.

PubMed

Tsuribe, Patrícia Miyuki; Lima Neto, João Ferreira; Golim, Marjorie de Assis; Dell'Aqua, Camila de Paula Freitas; Issa, João Paulo; Gobbo, Carlos Alberto Monte

2016-03-01

This study aimed to produce data on sperm quality while maintaining the integrity of sperm DNA samples taken from patients submitted to in vitro fertilization (IVF) procedures at our center, and determine whether increased levels of histones were associated with sperm DNA damage and decreased fertilization, cleavage, and pregnancy rates. Such findings might shed light on the physiology and outcomes of pregnancy. Semen samples from 27 patients divided into two groups were analyzed. The case group included individuals offered IVF; the control group had subjects with normal spermograms. Sperm DNA structure was assessed through phosphorylated histone H2AX analysis by flow cytometry. The patients with altered sperm parameters had more histones in sperm chromatin than the individuals with normal sperm parameters. Results indicated that increased levels of histone in sperm chromatin do not affect embryo production, but affect the cleavage rate, embryo quality, and might thus reduce pregnancy rates. The integrity of the paternal genome is of paramount importance in the initiation and maintenance of a viable pregnancy in patients treated with assisted reproduction technology procedures. Further studies on sperm diagnostic tests at a nuclear level might improve the treatment offered to infertile couples.

The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors.

PubMed

Hulmi, Juha J; Isola, Ville; Suonpää, Marianna; Järvinen, Neea J; Kokkonen, Marja; Wennerström, Annika; Nyman, Kai; Perola, Markus; Ahtiainen, Juha P; Häkkinen, Keijo

2016-01-01

Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight ( P < 0.001) and a ~35-50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet ( P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone ( P < 0.001), and estradiol ( P < 0.01) coinciding with an increased incidence of menstrual irregularities ( P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3-4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35-50% decrease in body fat in previously normal-weight females can recover within 3-4 months of increased energy intake.

The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors

PubMed Central

Hulmi, Juha J.; Isola, Ville; Suonpää, Marianna; Järvinen, Neea J.; Kokkonen, Marja; Wennerström, Annika; Nyman, Kai; Perola, Markus; Ahtiainen, Juha P.; Häkkinen, Keijo

2017-01-01

Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35–50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3–4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35–50% decrease in body fat in previously normal-weight females can recover within 3–4 months of increased energy intake. PMID:28119632

Shadow Areas Robust Matching Among Image Sequence in Planetary Landing

NASA Astrophysics Data System (ADS)

Ruoyan, Wei; Xiaogang, Ruan; Naigong, Yu; Xiaoqing, Zhu; Jia, Lin

2017-01-01

In this paper, an approach for robust matching shadow areas in autonomous visual navigation and planetary landing is proposed. The approach begins with detecting shadow areas, which are extracted by Maximally Stable Extremal Regions (MSER). Then, an affine normalization algorithm is applied to normalize the areas. Thirdly, a descriptor called Multiple Angles-SIFT (MA-SIFT) that coming from SIFT is proposed, the descriptor can extract more features of an area. Finally, for eliminating the influence of outliers, a method of improved RANSAC based on Skinner Operation Condition is proposed to extract inliers. At last, series of experiments are conducted to test the performance of the approach this paper proposed, the results show that the approach can maintain the matching accuracy at a high level even the differences among the images are obvious with no attitude measurements supplied.

Behaviours associated with weight loss maintenance and regaining in a Mediterranean population sample. A qualitative study.

PubMed

Karfopoulou, E; Mouliou, K; Koutras, Y; Yannakoulia, M

2013-10-01

In the US, the National Weight Control Registry revealed lifestyle behaviours shared by weight loss maintainers. In the US and the UK, qualitative studies compared the experiences of weight loss maintainers and regainers. High rates of physical activity, a low-energy/low-fat diet, weight self-monitoring, breakfast consumption and flexible control of eating are well-established maintenance behaviours. The Mediterranean lifestyle has not been studied relative to weight loss maintenance. This study focused on a sample of Greek maintainers and regainers. Maintainers emphasized home-cooked meals; their diet does not appear to be low-fat, as home-cooked Greek meals are rich in olive oil. Having a small dinner is a common strategy among maintainers. Health motives were not mentioned by maintainers. Maintainers, but not regainers, appeared to compensate for emotional eating. Weight loss maintenance is imperative to successful obesity treatment. We qualitatively explored lifestyle behaviours associated with weight regulation, in a sample of Greek volunteers who had lost weight and either maintained or regained it. A 10% intentional loss maintained for at least one year was considered successful maintenance. Volunteers (n = 44, 41% men) formed eight focus groups, four of maintainers and four of regainers. Questions regarded weight loss, weight maintenance or regaining, and beliefs on weight maintenance and regaining. All discussions were tape recorded. Maintainers lost weight on their own, whereas regainers sought professional help. Maintainers exercised during both the loss and maintenance phases, whereas regainers showed inconsistent physical activity levels. Health motives for weight loss were mentioned only by regainers. Emotional eating was a common barrier, but only maintainers compensated for it. Maintainers continuously applied specific strategies to maintain their weight: emphasizing home-cooked meals, high eating frequency, a small dinner, portion size regulation, and sweets' intake regulation. Regainers considered the behaviours leading to weight loss different from their normal lifestyle, and resumed their old habits when the diet was over. However, both groups believed that for long-term success, lifestyle changes need to be permanent. © 2013 The Authors. Clinical Obesity © 2013 International Association for the Study of Obesity.

[Energy corrective and antioxidative actions of cytoflavin during postischemic period of human dermal fibroblasts in vitro].

PubMed

Tiuriaeva, I I; Kuranova, M L; Gonchar, I V; Rozanov, Iu M

2012-01-01

The influence of metabolic drug Cytoflavin (CF) with antihypoxic and antioxidative properties on human dermal fibroblasts in a model of ischemia-reoxygenation in vitro was studied. It was revealed that the restoration of ATP synthesis in fibroblasts in the postischemic period was considerably accelerated (in 2.1 times) by the addition of CF to the culture medium. The drug had a cell protective effect of reducing cell mortality during the reoxygenation after ischemia by 2-2.7 times. CF effectively reduced the level of reactive oxygen species (ROS) in fibroblasts after H2O2 treatment which allowed maintaining their survival at the level of control cells. Pretreatment of the cells with CF for one day ensured the maintenance of normal levels of ROS during the investigated time period in the fibroblasts subjected to H2O2 treatment, and reduced H2O2-induced cell death by almost a third compared to control cells. The introduction of CF in culture medium after ischemia showed no influence on Hsp70 synthesis, but led to decrease in GRP78 synthesis, raised after ischemia, to the control level, indicating a resolve of the endoplasmic reticulum (ER) stress and functional normalization of ER.

S-ADENOSYLMETHIONINE IN LIVER HEALTH, INJURY, AND CANCER

PubMed Central

Lu, Shelly C.; Mato, José M.

2013-01-01

S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well. PMID:23073625

Wireless connection of continuous glucose monitoring system to the electronic patient record

NASA Astrophysics Data System (ADS)

Murakami, Alexandre; Gutierrez, Marco A.; Lage, Silvia G.; Rebelo, Marina S.; Granja, Luiz A. R.; Ramires, Jose A. F.

2005-04-01

The control of blood sugar level (BSL) at near-normal levels has been documented to reduce both acute and chronic complications of diabetes mellitus. Recent studies suggested, the reduction of mortality in a surgical intensive care unit (ICU), when the BSL are maintained at normal levels. Despite of the benefits appointed by these and others clinical studies, the strict BSL control in critically ill patients suffers from some difficulties: a) medical staff need to measure and control the patient"s BSL using blood sample at least every hour. This is a complex and time consuming task; b) the inaccuracy of standard capillary glucose monitoring (fingerstick) in hypotensive patients and, if frequently used to sample arterial or venous blood, may lead to excess phlebotomy; c) there is no validated procedure for continuously monitoring of BSL levels. This study used the MiniMed CGMS in ill patients at ICU to send, in real-time, BSL values to a Web-Based Electronic Patient Record. The BSL values are parsed and delivered through a wireless network as an HL7 message. The HL7 messages with BSL values are collected, stored into the Electronic Patient Record and presented into a bed-side monitor at the ICU together with other relevant patient information.

Reversal of Physiological Deficits Caused by Diminished Levels of Peptidylglycine α-Amidating Monooxygenase by Dietary Copper

PubMed Central

Bousquet-Moore, D.; Ma, X. M.; Nillni, E. A.; Czyzyk, T. A.; Pintar, J. E.; Eipper, B. A.; Mains, R. E.

2009-01-01

Amidated peptides are critically involved in many physiological functions. Genetic deletion of peptidylglycine α-amidating monooxygenase (PAM), the only enzyme that can synthesize these peptides, is embryonically lethal. The goal of the present study was the identification of physiological functions impaired by haploinsufficiency of PAM. Regulation of the hypothalamic-pituitary-thyroid axis and body temperature, functions requiring contributions from multiple amidated peptides, were selected for evaluation. Based on serum T4 and pituitary TSH-β mRNA levels, mice heterozygous for PAM (PAM+/−) were euthyroid at baseline. Feedback within the hypothalamic-pituitary-thyroid axis was impaired in PAM+/− mice made hypothyroid using a low iodine/propylthiouracil diet. Despite their normal endocrine response to cold, PAM+/− mice were unable to maintain body temperature as well as wild-type littermates when kept in a 4 C environment. When provided with additional dietary copper, PAM+/− mice maintained body temperature as well as wild-type mice. Pharmacological activation of vasoconstriction or shivering also allowed PAM+/− mice to maintain body temperature. Cold-induced vasoconstriction was deficient in PAM+/− mice. This deficit was eliminated in PAM+/− mice receiving a diet with supplemental copper. These results suggest that dietary deficiency of copper, coupled with genetic deficits in PAM, could result in physiological deficits in humans. PMID:19022883

Serum-Free Medium and Mesenchymal Stromal Cells Enhance Functionality and Stabilize Integrity of Rat Hepatocyte Spheroids

PubMed Central

Bao, Ji; Fisher, James E.; Lillegard, Joseph B.; Wang, William; Amiot, Bruce; Yu, Yue; Dietz, Allan B.; Nahmias, Yaakov; Nyberg, Scott L.

2013-01-01

Long-term culture of hepatocyte spheroids with high ammonia clearance is valuable for therapeutic applications, especially the bioartificial liver. However, the optimal conditions are not well studied. We hypothesized that liver urea cycle enzymes can be induced by high protein diet and maintain on a higher expression level in rat hepatocyte spheroids by serum-free medium (SFM) culture and coculture with mesenchymal stromal cells (MSCs). Rats were feed normal protein diet (NPD) or high protein diet (HPD) for 7 days before liver digestion and isolation of hepatocytes. Hepatocyte spheroids were formed and maintained in a rocked suspension culture with or without MSCs in SFM or 10% serum-containing medium (SCM). Spheroid viability, kinetics of spheroid formation, hepatic functions, gene expression, and biochemical activities of rat hepatocyte spheroids were tested over 14 days of culture. We observed that urea cycle enzymes of hepatocyte spheroids can be induced by high protein diet. SFM and MSCs enhanced ammonia clearance and ureagenesis and stabilized integrity of hepatocyte spheroids compared to control conditions over 14 days. Hepatocytes from high protein diet-fed rats formed spheroids and maintained a high level of ammonia detoxification for over 14 days in a novel SFM. Hepatic functionality and spheroid integrity were further stabilized by coculture of hepatocytes with MSCs in the spheroid microenvironment. These findings have direct application to development of the spheroid reservoir bioartificial liver. PMID:23006214

Diagnosis and management of subclinical hypothyroidism in pregnancy.

PubMed

Negro, Roberto; Stagnaro-Green, Alex

2014-10-06

In prospective studies, the prevalence of undiagnosed subclinical hypothyroidism in pregnant women ranges from 3% to 15%. Subclinical hypothyroidism is associated with multiple adverse outcomes in the mother and fetus, including spontaneous abortion, pre-eclampsia, gestational hypertension, gestational diabetes, preterm delivery, and decreased IQ in the offspring. Only two prospective studies have evaluated the impact of levothyroxine therapy in pregnant women with subclinical hypothyroidism, and the results were mixed. Subclinical hypothyroidism is defined as raised thyrotropin combined with a normal serum free thyroxine level. The normal range of thyrotropin varies according to geographic region and ethnic background. In the absence of local normative data, the recommended upper limit of thyrotropin in the first trimester of pregnancy is 2.5 mIU/L, and 3.0 mIU/L in the second and third trimester. The thyroid gland needs to produce 50% more thyroid hormone during pregnancy to maintain a euthyroid state. Consequently, most women on levothyroxine therapy before pregnancy require an increase in dose when pregnant to maintain euthyroidism. Ongoing prospective trials that are evaluating the impact of levothyroxine therapy on adverse outcomes in the mother and fetus in women with subclinical hypothyroidism will provide crucial data on the role of thyroid hormone replacement in pregnancy. © BMJ Publishing Group Ltd 2014.

Oil cooling system for a gas turbine engine

NASA Technical Reports Server (NTRS)

Coffinberry, G. A.; Kast, H. B. (Inventor)

1977-01-01

A gas turbine engine fuel delivery and control system is provided with means to recirculate all fuel in excess fuel control requirements back to the aircraft fuel tank. This increases the fuel pump heat sink and decreases the pump temperature rise without the addition of valving other than normally employed. A fuel/oil heat exchanger and associated circuitry is provided to maintain the hot engine oil in heat exchange relationship with the cool engine fuel. Where anti-icing of the fuel filter is required, means are provided to maintain the fuel temperature entering the filter at or above a minimum level to prevent freezing thereof. In one embodiment, a divider valve is provided to take all excess fuel from either upstream or downstream of the fuel filter and route it back to the tanks, the ratio of upstream to downstream extraction being a function of fuel pump discharge pressure.

High temperature acoustic levitator

NASA Technical Reports Server (NTRS)

Barmatz, M. B. (Inventor)

1984-01-01

A system is described for acoustically levitating an object within a portion of a chamber that is heated to a high temperature, while a driver at the opposite end of the chamber is maintained at a relatively low temperature. The cold end of the chamber is constructed so it can be telescoped to vary the length (L sub 1) of the cold end portion and therefore of the entire chamber, so that the chamber remains resonant to a normal mode frequency, and so that the pressure at the hot end of the chamber is maximized. The precise length of the chamber at any given time, is maintained at an optimum resonant length by a feedback loop. The feedback loop includes an acoustic pressure sensor at the hot end of the chamber, which delivers its output to a control circuit which controls a motor that varies the length (L) of the chamber to a level where the sensed acoustic pressure is a maximum.

Early adaptation to altered gravitational environments in the squirrel monkey

NASA Technical Reports Server (NTRS)

Fuller, C. A.

1985-01-01

The feeding behavior of two squirrel monkeys flown in Spacelab 3 is compared to that of six monkeys exposed to 1.5 G through centrifugation. The monkeys in the centrifugation study were housed unrestrained in cages, maintained at 25 C + or - 1 C, exposed to a 12:12 light/dark cycle, and had unrestrained access to food and water. The Spacelab monkeys were maintained at 26 C, exposed to a 12:12 light/dark cycle and had unlimited food and water. It is observed that the centrifuge rats displayed a change in feeding behavior for 4 days prior to resuming a normal pattern; one Spacelab monkey exhibited a 6 day depression before recover to control levels, and the feeding pattern of the second monkey was not influenced by the environment. It is noted that the effect of an altered dynamic environment is variable on the feeding behavior of individual monkeys.

eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor cells

PubMed Central

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R.; Beadnell, Thomas C.; Schwertfeger, Kathryn L.; Benyumov, Alexey O.; Manivel, J. Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B.; Polunovsky, Vitaly A.

2015-01-01

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biological outputs remains unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased cell self-renewal, triggered DNA replication stress, and induced formation of pre-malignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands, and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its pro-neoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. PMID:25524901

Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis

PubMed Central

HajMohammadi, Sassan; Enjyoji, Keiichi; Princivalle, Marc; Christi, Patricia; Lech, Miroslav; Beeler, David; Rayburn, Helen; Schwartz, John J.; Barzegar, Samad; de Agostini, Ariane I.; Post, Mark J.; Rosenberg, Robert D.; Shworak, Nicholas W.

2003-01-01

Endothelial cell production of anticoagulant heparan sulfate (HSact) is controlled by the Hs3st1 gene, which encodes the rate-limiting enzyme heparan sulfate 3-O-sulfotransferase-1 (3-OST-1). In vitro, HSact dramatically enhances the neutralization of coagulation proteases by antithrombin. The in vivo role of HSact was evaluated by generating Hs3st1–/– knockout mice. Hs3st1–/– animals were devoid of 3-OST-1 enzyme activity in plasma and tissue extracts. Nulls showed dramatic reductions in tissue levels of HSact but maintained wild-type levels of tissue fibrin accumulation under both normoxic and hypoxic conditions. Given that vascular HSact predominantly occurs in the subendothelial matrix, mice were subjected to a carotid artery injury assay in which ferric chloride administration induces de-endothelialization and occlusive thrombosis. Hs3st1–/– and Hs3st1+/+ mice yielded indistinguishable occlusion times and comparable levels of thrombin•antithrombin complexes. Thus, Hs3st1–/– mice did not show an obvious procoagulant phenotype. Instead, Hs3st1–/– mice exhibited genetic background–specific lethality and intrauterine growth retardation, without evidence of a gross coagulopathy. Our results demonstrate that the 3-OST-1 enzyme produces the majority of tissue HSact. Surprisingly, this bulk of HSact is not essential for normal hemostasis in mice. Instead, 3-OST-1–deficient mice exhibited unanticipated phenotypes suggesting that HSact or additional 3-OST-1–derived structures may serve alternate biologic roles. PMID:12671048

Physiological Ranges of Matrix Rigidity Modulate Primary Mouse Hepatocyte Function In Part Through Hepatocyte Nuclear Factor 4 Alpha

PubMed Central

Desai, Seema S.; Tung, Jason C.; Zhou, Vivian X.; Grenert, James P.; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M.; Chang, Tammy T.

2016-01-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of hepatic-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150Pa and increased to 1–6kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α) whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase (FAK). In addition, blockade of the Rho/Rho-associated protein kinase (ROCK) pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/ROCK pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. PMID:26755329

eIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

PubMed

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R; Beadnell, Thomas C; Schwertfeger, Kathryn L; Benyumov, Alexey O; Manivel, J Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2015-02-15

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. ©2014 American Association for Cancer Research.

Apparatus for controlling coolant level in a liquid-metal-cooled nuclear reactor

DOEpatents

Jones, Robert D.

1978-01-01

A liquid-metal-cooled fast-breeder reactor which has a thermal liner spaced inwardly of the pressure vessel and includes means for passing bypass coolant through the annulus between the thermal liner and the pressure vessel to insulate the pressure vessel from hot outlet coolant includes control ports in the thermal liner a short distance below the normal operating coolant level in the reactor and an overflow nozzle in the pressure vessel below the control ports connected to an overflow line including a portion at an elevation such that overflow coolant flow is established when the coolant level in the reactor is above the top of the coolant ports. When no makeup coolant is added, bypass flow is inwardly through the control ports and there is no overflow; when makeup coolant is being added, coolant flow through the overflow line will maintain the coolant level.

Differential regulation of glutathione peroxidase by selenomethionine and hyperoxia in endothelial cells.

PubMed Central

Jornot, L; Junod, A F

1995-01-01

We have studied the effect of selenomethionine (SeMet) and hyperoxia on the expression of glutathione peroxidase (GP) in human umbilical vein endothelial cells. Incubation of HUVEC with 1 x 10(-6) M SeMet for 24 h and 48 h caused a 65% and 86% increase in GP activity respectively. The same treatment did not result in significant changes in GP gene transcription and mRNA levels. Pactamycin, a specific inhibitor of the initiation step of translation, prevented the rise in GP activity induced by SeMet and caused an increase in GP mRNA in both cells grown in normal and SeMet-supplemented medium. Interestingly, SeMet supplementation stimulated the recruitment of GP mRNA from an untranslatable pool on to polyribosomes, so that the concentration of GP mRNA in polyribosomal translatable pools was 50% higher in cells grown in SeMet-supplemented medium than in cells grown in normal medium. On the other hand, cells exposed to 95% O2 for 3 days in normal medium showed a 60%, 394% and 81% increase in GP gene transcription rate, mRNA levels and activity respectively. Hyperoxia also stabilized GP mRNA. Hyperoxic cells grown in SeMet-supplemented medium did not show any change in GP gene transcription and mRNA levels, but expressed an 81% and 100% increase in GP activity and amount of GP mRNA associated with polyribosomes respectively, when compared with hyperoxic cells maintained in normal medium. Thus, GP appeared to be regulated post-transcriptionally, most probably co-translationally, in response to selenium availability, and transcriptionally and post-transcriptionally in response to oxygen. Images Figure 1 Figure 2 Figure 4 Figure 7 Figure 8 PMID:7887914

Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.

PubMed

Suzuki, Ayako; Lindor, Keith; St Saver, Jenny; Lymp, James; Mendes, Flavia; Muto, Ayako; Okada, Toshihide; Angulo, Paul

2005-12-01

The effects of lifestyle modifications in nonalcoholic fatty liver disease (NAFLD) are incompletely defined. We aimed at determining the association of changes in body weight and lifestyle with changes in serum ALT levels. We analyzed annual health checkup data from 1546 employees. Of 469 subjects with elevated ALT, we selected 348 male subjects by excluding those who had other causes of liver disease. They were followed for one year to assess the association of change in lifestyle with change in serum ALT. The 136 subjects who had ALT normalization were followed for two years to assess the association between lifestyle management and persistently normal ALT. In adjusted analysis, weight loss and regular exercise were significantly associated with improvement in serum ALT and increased the odds of ALT normalization, while starting smoking was significantly associated with deterioration in serum ALT. Subjects achieving > or = 5% weight reduction showed improvement in serum ALT. Reduction in alcohol consumption was not associated with changes in serum ALT. Maintaining reduced weight (<5% gain) was significantly associated with persistently normal ALT. Reducing weight by at least 5% with subsequent weight control and exercising regularly may be beneficial in treating NAFLD.

The histamine-synthesizing enzyme histidine decarboxylase is upregulated by keratinocytes in atopic skin.

PubMed

Gutowska-Owsiak, D; Greenwald, L; Watson, C; Selvakumar, T A; Wang, X; Ogg, G S

2014-10-01

Histamine is an abundant mediator accumulating in the skin of atopic patients, where it is thought to be derived from immune cells. While keratinocytes express histidine decarboxylase (HDC), levels of the enzyme in normal or diseased epidermis and factors that influence its expression in human keratinocytes are not known. To assess levels of HDC in inflammatory skin diseases and factors influencing its expression. Normal and filaggrin-insufficient human keratinocytes, organotypic epidermal models and skin samples were investigated for the expression of HDC. The effect of cytokines, bacterial and allergen stimuli exposure and functional changes in differentiation were evaluated in vitro. We detected abundant expression of the HDC protein in all models studied; expression was increased in atopic skin samples. Filaggrin-insufficient keratinocytes maintained HDC levels, but exposure of keratinocytes to thymic stromal lymphopoietin, tumour necrosis factor-α, lipopolysaccharide (LPS) and house dust mite (HDM) extract increased HDC expression in vitro. Furthermore, filaggrin expression in cultured keratinocytes increased following histamine depletion. Keratinocytes express abundant HDC protein, and the levels increase in atopic skin. LPS, HDM and cytokines, which are implicated in allergic inflammation, promote the expression of the enzyme and upregulate histamine levels in keratinocytes. Actively produced histamine influences keratinocyte differentiation, suggesting functional relevance of the axis to atopic dermatitis. The findings therefore identify a new point of therapeutic intervention. © 2014 British Association of Dermatologists.

Low-pressure oxidation of Cb-1Zr alloy.

NASA Technical Reports Server (NTRS)

Lyon, T. F.

1971-01-01

Resistively heated strip specimens of Cb-1Zr alloy were exposed at 927 C in a vacuum chamber at various levels of total pressure in the 1-microtorr range and at various oxygen partial pressures in the .1-microtorr range. Oxygen reaction rates (sticking probabilities) were found to depend on whether or not the specimens were annealed immediately before the test exposure. It is shown that a normally undetectable oxide film exists on the Cb-1Zr surface as a result of oxidation by ambient air, and this film reduces the sticking probability as compared with a clean metal surface. The alloy is considerably strengthened by addition of oxygen to a level of about 6000 ppm, while still maintaining reasonably good room temperature ductility.

Polyamines and cancer: Implications for chemoprevention and chemotherapy

PubMed Central

Nowotarski, Shannon L.; Woster, Patrick M.; Casero, Robert A.

2013-01-01

Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes and a poorly characterized transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate, and skin cancers, and altered levels of the rate limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway specific drugs, and ongoing clinical trials targeting polyamine biosynthesis. PMID:23432971

16S rDNA analysis of the effect of fecal microbiota transplantation on pulmonary and intestinal flora.

PubMed

Liu, Tianhao; Yang, Zhongshan; Zhang, Xiaomei; Han, Niping; Yuan, Jiali; Cheng, Yu

2017-12-01

This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated Proteobacteria , Firmicutes , and Bacteroidetes in the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas , Sphingobium , Lactobacillus , Rhizobium , and Acinetobacter , thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases.

Static Feed Water Electrolysis Subsystem Testing and Component Development

NASA Technical Reports Server (NTRS)

Koszenski, E. P.; Schubert, F. H.; Burke, K. A.

1983-01-01

A program was carried out to develop and test advanced electrochemical cells/modules and critical electromechanical components for a static feed (alkaline electrolyte) water electrolysis oxygen generation subsystem. The accomplishments were refurbishment of a previously developed subsystem and successful demonstration for a total of 2980 hours of normal operation; achievement of sustained one-person level oxygen generation performance with state-of-the-art cell voltages averaging 1.61 V at 191 ASF for an operating temperature of 128F (equivalent to 1.51V when normalized to 180F); endurance testing and demonstration of reliable performance of the three-fluid pressure controller for 8650 hours; design and development of a fluid control assembly for this subsystem and demonstration of its performance; development and demonstration at the single cell and module levels of a unitized core composite cell that provides expanded differential pressure tolerance capability; fabrication and evaluation of a feed water electrolyte elimination five-cell module; and successful demonstration of an electrolysis module pressurization technique that can be used in place of nitrogen gas during the standby mode of operation to maintain system pressure and differential pressures.

Basic Proteins of Plant Nuclei during Normal and Pathological Cell Growth

PubMed Central

Rasch, Ellen; Woodard, John W.

1959-01-01

Histone proteins were studied by microphotometry of plant tissue sections stained with fast green at pH 8.1. For comparative purposes the Feulgen reaction was used for deoxyribose nuclei acid (DNA); the Sakaguchi reaction for arginine; and the Millon reaction for estimates of total protein. Analysis of Tradescantia tissues indicated that amounts of nuclear histone fell into approximate multiples of the gametic (egg or sperm) quantity except in dividing tissues, where amounts intermediate between multiples were found. In differentiated tissues of lily, corn, onion, and broad bean, histones occurred in constant amounts per nucleus, characteristic of the species, as was found also for DNA. Unlike the condition in several animal species, the basic proteins of sperm nuclei in these higher plants were of the histone type; no evidence of protamine was found. In a plant neoplasm, crown gall of broad bean, behavior of the basic nuclear proteins closely paralleled that of DNA. Thus, alterations of DNA levels in tumor tissues were accompanied by quantitatively similar changes in histone levels to maintain the same Feulgen/fast green ratios found in homologous normal tissues. PMID:14436319

31 CFR 515.509 - Entries in certain accounts for normal service charges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... against any foreign currency account maintained by it with a banking institution in a designated foreign... therewith. (b) As used in this section, the term normal service charge shall include charges in payment or...

31 CFR 585.520 - Entries in certain accounts for normal service charges authorized.

Code of Federal Regulations, 2010 CFR

2010-07-01

... account; and (2) Make book entries against any foreign currency account maintained by it with a financial... charges in connection therewith. (b) As used in this section, the term normal service charge shall include...

31 CFR 500.509 - Entries in certain accounts for normal service charges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... against any foreign currency account maintained by it with a banking institution in any designated foreign... therewith. (b) As used in this section, the term normal service charge shall include charges in payment or...

The slippery slope: prediction of successful weight maintenance in anorexia nervosa

PubMed Central

Kaplan, A. S.; Walsh, B. T.; Olmsted, M.; Attia, E.; Carter, J. C.; Devlin, M. J.; Pike, K. M.; Woodside, B.; Rockert, W.; Roberto, C. A.; Parides, M.

2015-01-01

Background Previous research has found that many patients with anorexia nervosa (AN) are unable to maintain normal weight after weight restoration. The objective of this study was to identify variables that predicted successful weight maintenance among weight-restored AN patients. Method Ninety-three patients with AN treated at two sites (Toronto and New York) through in-patient or partial hospitalization achieved a minimally normal weight and were then randomly assigned to receive fluoxetine or placebo along with cognitive behavioral therapy (CBT) for 1 year. Clinical, demographic and psychometric variables were assessed after weight restoration prior to randomization and putative predictors of successful weight maintenance at 6 and 12 months were examined. Results The most powerful predictors of weight maintenance at 6 and 12 months following weight restoration were pre-randomization body mass index (BMI) and the rate of weight loss in the first 28 days following randomization. Higher BMI and lower rate of weight loss were associated with greater likelihood of maintaining a normal BMI at 6 and 12 months. An additional predictor of weight maintenance was site; patients in Toronto fared better than those in New York. Conclusions This study found that the best predictors of weight maintenance in weight-restored AN patients over 6 and 12 months were the level of weight restoration at the conclusion of acute treatment and the avoidance of weight loss immediately following intensive treatment. These results suggest that outcome might be improved by achieving a higher BMI during structured treatment programs and on preventing weight loss immediately following discharge from such programs. PMID:18845008

Respiratory mechanics and breathing pattern in the neonatal foal.

PubMed

Koterba, A M; Kosch, P C

1987-01-01

Breathing pattern, respiratory muscle activation pattern, lung volumes and volume-pressure characteristics of the respiratory system of normal, term, neonatal foals on Days 2 and 7 of age were determined to test the hypothesis that the foal actively maintains end-expiratory lung volume (EEV) greater than the relaxation volume of the respiratory system (Vrx) because of a highly compliant chest wall. Breathing pattern was measured in the awake, unsedated foal during quiet breathing in lateral and standing positions. The typical neonatal foal breathing pattern was characterized by a monophasic inspiratory and expiratory flow pattern. Both inspiration and expiration were active, with onset of Edi activity preceding onset of inspiratory flow, and phasic abdominal muscle activity detectable throughout most of expiration. No evidence was found to support the hypothesis that the normal, term neonatal foal actively maintains EEV greater than Vrx. In the neonatal foal, normalized lung volume and lung compliance values were similar to those reported for neonates of other species, while normalized chest wall compliance was considerably lower. We conclude that the chest wall of the term neonatal foal is sufficiently rigid to prevent a low Vrx. This characteristic probably prevents the foal from having to use a breathing strategy which maintains an EEV greater than Vrx.

Glutathione-related enzymes and the eye.

PubMed

Ganea, Elena; Harding, John J

2006-01-01

Glutathione and the related enzymes belong to the defence system protecting the eye against chemical and oxidative stress. This review focuses on GSH and two key enzymes, glutathione reductase and glucose-6-phosphate dehydrogenase in lens, cornea, and retina. Lens contains a high concentration of reduced glutathione, which maintains the thiol groups in the reduced form. These contribute to lens complete transparency as well as to the transparent and refractive properties of the mammalian cornea, which are essential for proper image formation on the retina. In cornea, gluthatione also plays an important role in maintaining normal hydration level, and in protecting cellular membrane integrity. In retina, glutathione is distributed in the different types of retinal cells. Intracellular enzyme, glutathione reductase, involved in reducing the oxidized glutathione has been found at highest activity in human and primate lenses, as compared to other species. Besides the enzymes directly involved in maintaining the normal redox status of the cell, glucose-6-phosphate dehydrogenase which catalyzes the first reaction of the pentose phosphate pathway, plays a key role in protection of the eye against reactive oxygen species. Cornea has a high activity of the pentose phosphate pathway and glucose-6-phosphate dehydrogenase activity. Glycation, the non-enzymic reaction between a free amino group in proteins and a reducing sugar, slowly inactivates gluthathione-related and other enzymes. In addition, glutathione can be also glycated. The presence of glutathione, and of the related enzymes has been also reported in other parts of the eye, such as ciliary body and trabecular meshwork, suggesting that the same enzyme systems are present in all tissues of the eye to generate NADPH and to maintain gluthatione in the reduced form. Changes of glutathione and related enzymes activity in lens, cornea, retina and other eye tissues, occur with ageing, cataract, diabetes, irradiation and administration of some drugs.

Prevention of Iron Overload and Long Term Maintenance of Normal Iron Stores in Thalassaemia Major Patients using Deferiprone or Deferiprone Deferoxamine Combination.

PubMed

Kolnagou, Annita; Kontoghiorghe, Christina N; Kontoghiorghes, George J

2017-07-01

Decrease in mortality and morbidity is observed in thalassaemia major patients with reduced iron load in comparison to heavy iron loaded patients. Effective and complete treatment of transfusional iron overload can be achieved by chelation protocols that can eliminate excess iron and maintain normal iron stores (NIS). The maintenance of NIS, i. e., serum ferritin (350 μg/L >), MRI T2* cardiac (>20 ms) and liver (>6.3 ms) relaxation time levels was monitored in 16 thalassaemia major patients (32-53 years, 12 splenectomized, 10 male, erythrocyte transfusions 120-323 ml/kg/year) for about 90 patient years. The patients were treated with individualised tailor-made deferiprone or deferiprone/deferoxamine combination protocols. In 8 patients deferiprone (50-100 mg/kg/day) was sufficient for maintaining NIS and withdrawal of deferiprone for 28 months in total was necessary in 4 patients for preventing iron deficiency. In 3 other patients intermittent deferoxamine (50-75 mg/kg/8-30 h, 1-4 days/week) in combination with deferiprone (75-100 mg/kg/day) was sufficient for maintaining NIS. In the remaining 5 patients deferiprone (75-100 mg/kg/day) and deferoxamine (50-60 mg/kg/8-15 h, 1-7 days/week) combination was used for maintaining NIS, as a result of increased transfusions which were caused mainly by splenomegaly and infections. No toxic side effects were detected during the study. Lower chelation doses were used for the maintenance of NIS in comparison to iron loaded categories of patients. The safe maintenance of NIS using deferiprone and deferiprone/deferoxamine combinations should be considered as an optimum therapy for the complete treatment of iron overload in the majority of thalassaemia patients. © Georg Thieme Verlag KG Stuttgart · New York.

Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.

PubMed

More, Amar S; Mishra, Jay S; Hankins, Gary D; Kumar, Sathish

2016-08-01

Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na(+) and K(+) levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg(8)-vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na(+) and K(+) levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na(+) and K(+) levels and mediate hypertension in adult testosterone females. © 2016 by the Society for the Study of Reproduction, Inc.

Reduced Solubility of Polymer-Oriented Water for Sodium Salts, Sugars, Amino Acids, and other Solutes Normally Maintained at Low Levels in Living Cells,

DTIC Science & Technology

1983-01-01

following were obtained: gum arabic (64C-0252; gum ghatti (42C-2380; gum guar (32C1930); gum Karaya (103C-0720); gum locust bean (42C-2900); gum ...plotted against time of incubation. In the efflux method, usually the dry polymer powder was dissolved 22 + 35 in water containing the radioactive label...tragacanth (74C-0207); and gum xantham (888-0200); corn starch (6813-0216); potato starch (65B-2060); pectin (107B-0090); alginic acid (766-818); also

Use of outsourced nurses in long-term acute care hospitals: outcomes and leadership preferences.

PubMed

Alvarez, M Raymond; Kerr, Bernard J; Burtner, Joan; Ledlow, Gerald; Fulton, Larry V

2011-02-01

When staffing effectiveness is not maintained over time, the likelihood of negative outcomes increases. This challenge is particularly problematic in long-term acute care hospitals (LTACHs) where use of outsourced temporary nurses is common when providing safe, sufficient care to medically complex patients who require longer hospital stays than normally would occur. To assess this issue, the authors discuss the outcomes of their survey of LTACH chief nursing officers that demonstrated LTACH quality indicators and overall patient satisfaction were within nationally accepted benchmarks even with higher levels of outsourced nurses used in this post-acute care setting.

"Exercise dependence"--a problem or natural result of high activity?

PubMed

Phelan, Suzanne; Bond, Dale S; Lang, Wei; Jordan, Dustin; Wing, Rena R

2011-11-01

To compare physical activity (PA) and exercise dependence (ED) in 267 weight-loss maintainers (WLM) and 213 normal-weight (NW) controls. PA and ED assessed via accelerometery and the Exercise Dependence Questionnaire. WLM had higher PA levels and ED scores than those of NW (P< 0.0001). WLM status (P=.006) and higher PA (P=.0001) were independently related to higher ED, although effect sizes were larger for PA. Exercising for weight control was the ED domain that most discriminated WLM from NW. WLM have higher ED scores than do NW, but this is mostly due to exercising for weight control.

Hormonal Treatment of Transgender Women with Oral Estradiol.

PubMed

Leinung, Matthew C; Feustel, Paul J; Joseph, Jalaja

2018-01-01

Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

Effect of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of certain plasma enzymes in CCl4-induced liver injury in low-protein fed rats.

PubMed

Nkosi, C Z; Opoku, A R; Terblanche, S E

2005-04-01

The effects of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of lactate dehydrogenase (LD), alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) against carbon tetrachloride (CCl4)-induced acute liver injury in low-protein fed rats were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with pumpkin seed protein isolate. All three subgroups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all four enzymes were significantly higher than their counterparts on a normal balanced diet. CCl4 intoxication resulted in significant increases in the activity levels of all four enzymes investigated. The administration of pumpkin seed protein isolate after CCl4 intoxication resulted in significantly reduced activity levels of all four enzymes. It is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition. (c) 2005 John Wiley & Sons, Ltd.

Evaluation of a Low-Cost Bubble CPAP System Designed for Resource-Limited Settings.

PubMed

Bennett, Desmond J; Carroll, Ryan W; Kacmarek, Robert M

2018-04-01

Respiratory compromise is a leading contributor to global neonatal death. CPAP is a method of treatment that helps maintain lung volume during expiration, promotes comfortable breathing, and improves oxygenation. Bubble CPAP is an effective alternative to standard CPAP. We sought to determine the reliability and functionality of a low-cost bubble CPAP device designed for low-resource settings. The low-cost bubble CPAP device was compared to a commercially available bubble CPAP system. The devices were connected to a lung simulator that simulated neonates of 4 different weights with compromised respiratory mechanics (∼1, ∼3, ∼5, and ∼10 kg). The devices' abilities to establish and maintain pressure and flow under normal conditions as well as under conditions of leak were compared. Multiple combinations of pressure levels (5, 8, and 10 cm H 2 O) and flow levels (3, 6, and 10 L/min) were tested. The endurance of both devices was also tested by running the systems continuously for 8 h and measuring the changes in pressure and flow. Both devices performed equivalently during the no-leak and leak trials. While our testing revealed individual differences that were statistically significant and clinically important (>10% difference) within specific CPAP and flow-level settings, no overall comparisons of CPAP or flow were both statistically significant and clinically important. Each device delivered pressures similar to the desired pressures, although the flows delivered by both machines were lower than the set flows in most trials. During the endurance trials, the low-cost device was marginally better at maintaining pressure, while the commercially available device was better at maintaining flow. The low-cost bubble CPAP device evaluated in this study is comparable to a bubble CPAP system used in developed settings. Extensive clinical trials, however, are necessary to confirm its effectiveness. Copyright © 2018 by Daedalus Enterprises.

Use of structured personality survey techniques to indicate operator response to stressful situations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waller, M.A.

Under given circumstances, a person will tend to operate in one of four dominant orientations: (1) to perform tasks; (2) to achieve consensus; (3) to achieve understanding, or (4) to maintain structure. Historically, personality survey techniques, such as the Myers-Briggs type indicator, have been used to determine these tendencies. While these techniques can accurately reflect a person's orientation under normal social situations, under different sets of conditions, the same person may exhibit other tendencies, displaying a similar or entirely different orientation. While most do not exhibit extreme tendencies or changes of orientation, the shift in personality from normal to stressfulmore » conditions can be rather dramatic, depending on the individual. Structured personality survey techniques have been used to indicate operator response to stressful situations. These techniques have been extended to indicate the balance between orientations that the control room team has through the various levels of cognizance.« less

Genome-wide network analysis of Wnt signaling in three pediatric cancers

NASA Astrophysics Data System (ADS)

Bao, Ju; Lee, Ho-Jin; Zheng, Jie J.

2013-10-01

Genomic structural alteration is common in pediatric cancers, and analysis of data generated by the Pediatric Cancer Genome Project reveals such tumor-related alterations in many Wnt signaling-associated genes. Most pediatric cancers are thought to arise within developing tissues that undergo substantial expansion during early organ formation, growth and maturation, and Wnt signaling plays an important role in this development. We examined three pediatric tumors--medullobastoma, early T-cell precursor acute lymphoblastic leukemia, and retinoblastoma--that show multiple genomic structural variations within Wnt signaling pathways. We mathematically modeled this pathway to investigate the effects of cancer-related structural variations on Wnt signaling. Surprisingly, we found that an outcome measure of canonical Wnt signaling was consistently similar in matched cancer cells and normal cells, even in the context of different cancers, different mutations, and different Wnt-related genes. Our results suggest that the cancer cells maintain a normal level of Wnt signaling by developing multiple mutations.

The Production of lnterleukin-1 Receptor Antagonist by Human Bronchogenic Carcinoma

PubMed Central

Smith, Daniel R.; Kunkel, Steven L.; Standiford, Theodore J.; Chensue, Stephen W.; Rolfe, Mark W.; Orringer, Mark B.; Whyte, Richard I.; Burdick, Marie D.; Danforth, Jean M.; Gilbert, Andrew R.; Strieter, Robert M.

1993-01-01

Bronchogenic carcinoma displays an aggressive clinical course that may reflect a capacity to evade host defenses. We postulated that tumors may elaborate interleukin-1 receptor antagonist protein (IRAP) to escape host interleukin-1-dependent responses. Homogenates of human bronchogenic lung tumors demonstrated significant increases of IRAP compared with normal lung tissue controls (n = 48). There was no significant difference in interleukin-1 β levels between tumor and normal lung tissue. Immunohistochemical staining localized IRAP to tumor cells. Semiquantitative pathological analysis demonstrated a modest inflammatory cell infiltrate with qualitative differences between tumors of different histology. Western blot analysis of tumor homogenates demonstrated several molecular weight forms of IRAP. Finally, antigenic IRAP was detected in supernatants of the human bronchogenic carcinoma cell line (A549) maintained in vitro. These findings illustrate the capacity of bronchogenic tumors to produce and secrete IRAP that may be important in tumor evasion of host defenses. ImagesFigure 3Figure 4 PMID:8362978

Use of an Amino Acid Mixture in Treatment of Phenylketonuria

PubMed Central

Bentovim, A.; Clayton, Barbara E.; Francis, Dorothy E. M.; Shepherd, Jean; Wolff, O. H.

1970-01-01

Twelve children with phenylketonuria diagnosed and treated from the first few weeks of life were grouped into pairs. Before the trial all of them were receiving a commercial preparation containing a protein hydrolysate low in phenylalanine (Cymogran, Allen and Hanburys Ltd.) as a substitute for natural protein. One of each pair was given an amino acid mixture instead of Cymogran for about 6 months. Use of the mixture involved considerable modification of the diet, and in particular the inclusion of greater amounts of phenylalanine-free foods. All six accepted the new mixture without difficulty, food problems were greatly reduced, parents welcomed the new preparation, and the quality of family life improved. Normal growth was maintained and with a mixture of l amino acids the plasma and urinary amino acid levels were normal. Further studies are needed before the mixture can be recommended for children under 20 months of age. PMID:5477678

Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice

PubMed Central

Huai, Jisen; Firat, Elke; Nil, Ahmed; Million, Daniele; Gaedicke, Simone; Kanzler, Benoit; Freudenberg, Marina; van Endert, Peter; Kohler, Gabriele; Pahl, Heike L.; Aichele, Peter; Eichmann, Klaus; Niedermann, Gabriele

2008-01-01

The giant cytosolic protease tripeptidyl peptidase II (TPPII) has been implicated in the regulation of proliferation and survival of malignant cells, particularly lymphoma cells. To address its functions in normal cellular and systemic physiology we have generated TPPII-deficient mice. TPPII deficiency activates cell type-specific death programs, including proliferative apoptosis in several T lineage subsets and premature cellular senescence in fibroblasts and CD8+ T cells. This coincides with up-regulation of p53 and dysregulation of NF-κB. Prominent degenerative alterations at the organismic level were a decreased lifespan and symptoms characteristic of immunohematopoietic senescence. These symptoms include accelerated thymic involution, lymphopenia, impaired proliferative T cell responses, extramedullary hematopoiesis, and inflammation. Thus, TPPII is important for maintaining normal cellular and systemic physiology, which may be relevant for potential therapeutic applications of TPPII inhibitors. PMID:18362329

Hydrostatic pressure as epigenetic modulator in chondrocyte cultures: A study on miRNA-155, miRNA-181a and miRNA-223 expression levels.

PubMed

De Palma, Anna; Cheleschi, Sara; Pascarelli, Nicola Antonio; Giannotti, Stefano; Galeazzi, Mauro; Fioravanti, Antonella

2018-01-03

Mechanical stimuli and hydrostatic pressure (HP) play an important role in the regulation of chondrocytes metabolism. Growing evidence demonstrated the ability of mechanical loading to modulate the expression of microRNA (miRNA) involved in chondrocytes homeostasis and in the pathogenesis of osteoarthritis (OA). The expression of miR-155, miR-181a and miR-223 in normal and OA chondrocyte cultures, and their potential modifications following exposure to three hours of a cyclic HP (1-5 MPa, frequency 0.25 Hz) were investigated. Also evaluated the expression of Chuk, regulator of the NF-kB pathway activation, which is a target gene of miR-223, was evaluated. Chondrocytes were collected immediately after pressurization (T0), and following 12, 24, and 48 h. Total RNA was extracted, reverse transcribed and used for real-time PCR. At basal condition, a significant increase of miR-155 and miR-181a was observed in OA in comparison to normal cells; on the contrary, no differences in miR-223 and Chuk expression levels were detected between normal and OA chondrocytes. miR-155 and miR-181a resulted significantly downregulated immediately after pressurization (T0) in OA cells. The pressure effect on miR-155 and miR-181a levels was maintained over time. No modifications of miR-223 were observed in response to HP, while Chuk levels resulted significantly reduced at T0 and after 12 h. Pressurization did not cause any modifications in normal cells. In conclusion, HP was able to modulate the expression of miRNA associated to OA pathogenesis. The preliminary results about Chuk response to pressure raised interest in its involvement in the possible HP induced NF-kB pathway modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Supplemental levels of iron and calcium interfere with repletion of zinc status in zinc-deficient animals.

PubMed

Jayalakshmi, S; Platel, Kalpana

2016-05-18

Negative interactions between minerals interfering with each other's absorption are of concern when iron and calcium supplements are given to pregnant women and children. We have previously reported that supplemental levels of iron and calcium inhibit the bioaccessibility of zinc, and compromise zinc status in rats fed diets with high levels of these two minerals. The present study examined the effect of supplemental levels of iron and calcium on the recovery of zinc status during a zinc repletion period in rats rendered zinc-deficient. Iron and calcium, both individually and in combination, significantly interfered with the recovery of zinc status in zinc deficient rats during repletion with normal levels of zinc in the diet. Rats maintained on diets containing supplemental levels of these two minerals had significantly lower body weight, and the concentration of zinc in serum and organs was significantly lower than in zinc-deficient rats not receiving the supplements. Iron and calcium supplementation also significantly inhibited the activity of zinc-containing enzymes in the serum as well as liver. Both iron and calcium independently exerted this negative effect on zinc status, while their combination seemed to have a more prominent effect, especially on the activities of zinc containing enzymes. This investigation is probably the first systematic study on the effect of these two minerals on the zinc status of zinc deficient animals and their recovery during repletion with normal amounts of zinc.

Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells.

PubMed

Kim, Boyun; Kim, Hee Seung; Jung, Eun-Ji; Lee, Jung Yun; K Tsang, Benjamin; Lim, Jeong Mook; Song, Yong Sang

2016-05-01

Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells. © 2015 Wiley Periodicals, Inc.

Akt1/NFκB signaling pathway activation by a small molecule DMA confers radioprotection to intestinal epithelium in xenograft model.

PubMed

Tiwari, Vinod; Kamran, Mohammad Zahid; Ranjan, Atul; Nimesh, Hemlata; Singh, Manish; Tandon, Vibha

2017-07-01

Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism. Administration of single DMA dose prior to radiation has enhanced survival of Balb/c mice against sublethal and supralethal total body irradiation. DMA ameliorated radiation-induced damage of normal tissues such as hematopoietic (HP) and gastrointestinal tract (GI) system. Oxidative stress marker Malondialdehyde level was decreased by DMA whereas it maintained endogenous antioxidant status by increasing the level of reduced glutathione, glutathione reductase, glutathione-s-transferase, superoxide dismutase and total thiol content in hepatic tissue of irradiated mice. Mechanistic studies revealed that DMA treatment prior to radiation leads to Akt1/NFκB signaling which reduced radiation-induced genomic instability in normal cells. However, these pathways were not activated in tumor tissues when subjected to DMA treatment in similar conditions. Abrogation of Akt1 and NFκB genes resulted in no radioprotection by DMA and enhanced apoptosis against radiation. Plasma half-life of DMA was 3.5h and 2.65h at oral and intravenous dose respectively and 90% clearance was observed in 16h. In conclusion, these data suggests that DMA has potential to be developed as a safe radioprotective agent for radiation countermeasures and an adjuvant in cancer therapy. Copyright © 2017. Published by Elsevier Inc.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

PubMed

Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-12-01

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis. Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides). Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported. Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

9 CFR 3.80 - Primary enclosures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... injuring themselves; and (xi) Provide sufficient space for the nonhuman primates to make normal postural... maintained so as to provide sufficient space to allow each nonhuman primate to make normal postural... postural adjustments and movements within the primary enclosure. Different species of prosimians vary in...

STUDIES ON THE ORIGIN OF CIRCULATING 18-HYDROXYCORTISOL AND 18-OXOCORTISOL IN NORMAL HUMAN SUBJECTS.

PubMed Central

Freel, E Marie; Shakerdi, Loai A; Friel, Elaine C; Wallace, A Michael; Davies, Eleanor; Fraser, Robert; Connell, John MC

2005-01-01

18-hydroxycortisol (18-OHF) and 18-oxocortisol (18oxo-F) are derivatives of cortisol found in Primary Aldosteronism but whose origin and regulation in normal subjects is uncertain. 18-OHF can be synthesised by zona fasciculata 11-β hydroxylase; 18-oxoF can only be produced by zona glomerulosa aldosterone synthase (AS). Stably transfected cell lines expressing either CYP11B1 (11β-hydroxylase) or CYP11B2 (AS) were incubated with cortisol and other substrates over a range of concentrations. Both enzymes could synthesise 18-OHF from cortisol but only AS could synthesise 18-oxoF. AS was more efficient than 11β-hydroxylase at 18-hydroxylation. The apparent Km of AS for cortisol was estimated to be 2.6μM. In 5 patients with adrenal insufficiency maintained on hydrocortisone, urinary free cortisol and cortisone levels were high; 18-oxoF was detectable in all patients and 18-hydroxycortisol in 3. It is likely that the 18-oxygenated steroids were synthesised from circulating cortisol, either in the zona glomerulosa or at extra-adrenal sites. In 8 male volunteers, dexamethasone treatment decreased urinary excretion rates of free cortisol, cortisone, 18-OHF and 18-oxoFl, confirming dependence of 18-oxygenated steroid levels on cortisol availability. In both groups, hydrocortisone administration resulted in detectable levels of 18-OHF and raised levels of 18-oxoF. There was close correlation between 18-oxoF and cortisol excretion during hydrocortisone administration in normal subjects (r=0.86, p<0.001). These data show, for the first time, that 18-OHF and 18oxoF can be synthesised from circulating cortisol. The close correlation between 18-oxoF and cortisol suggests that 18-oxoF is normally produced by the action of aldosterone synthase utilising circulating cortisol as a substrate. Although 18OHF can be synthesized using circulating cortisol as substrate, our data suggest this is normally produced in the zona fasciculata by 11β-hydroxylase from locally available cortisol. PMID:15356073

Former Heroin Addicts with or without a History of Cocaine Dependence are more Impulsive than Controls

PubMed Central

Nielsen, David A.; Ho, Ann; Bahl, Ajay; Varma, Priya; Kellogg, Scott; Borg, Lisa; Kreek, Mary Jeanne

2012-01-01

Background Personality traits such as impulsivity and sensation seeking may contribute to the initiation and maintenance of illicit drug use. Since studies have reported higher impulsivity and sensation seeking traits in cocaine dependent subjects, we were interested in determining whether former heroin addicts in methadone pharmacotherapy with comorbid cocaine addiction have greater impulsivity than those without. Methods Instruments to assess impulsivity (Barratt Impulsiveness Scale version 11) and sensation seeking (Sensation Seeking Scale version V) were administered to former severe heroin addicts meeting Federal criteria for methadone maintenance pharmacotherapy with (n = 71) or without cocaine dependence (n = 31) and to 145 normal healthy (non-methadone-maintained) volunteers. Results The methadone-maintained without cocaine dependence and the methadone-maintained with cocaine dependence groups, both scored higher than did the normal volunteer group on the Barratt Impulsiveness Scale total score (p < 0.001). On the Barratt Impulsiveness Scale Attentional, Nonplanning, and Motor subscales, the methadone-maintained and methadone-maintained with cocaine dependence groups scored higher than did normal volunteers with no history of drug abuse or dependence (p < 0.001). There was no difference among groups on total score or any subscale of the Sensation Seeking Scale. However, males in all groups overall scored higher than did females on Disinhibition and Thrill and Adventure seeking subscales of the Sensation Seeking Scale version V (p < 0.001). Conclusions This study demonstrates higher impulsivity in former severe heroin addicts meeting criteria for or currently in stable methadone maintenance pharmacotherapy, irrespective of a positive or negative history of cocaine dependence. PMID:22265192

Organizational and individual factors influencing job satisfaction and burnout of mental health workers.

PubMed

Martin, U; Schinke, S P

1998-01-01

Job satisfaction and burnout are important areas of study because of the financial and social effects of job satisfaction and the damaging physical/psychological impacts of burnout. Two hundred family/children and psychiatric workers of seven social service organizations were surveyed. Instruments used were the Minnesota Satisfaction Questionnaire, the Maslach Burnout Inventory, and the Staff Burnout Scale for Health Professionals. Reported levels of job satisfaction and burnout are within normal limits. Psychiatric and family/children workers report equal job satisfaction levels, but the latter group reports significantly higher burnout levels. Both groups are particularly satisfied with the amount of praise delivered by supervisors and are reportedly dissatisfied with salary levels and promotional opportunities. These three factors are strongly associated with job satisfaction and burnout levels of both groups. Findings have practical implications for social service administrators and practitioners. Correlates of satisfaction and burnout can be altered in order to maintain employee satisfaction and reduce burnout, absenteeism and turnover.

Managing Children's Fears and Anxieties in Classroom Settings.

ERIC Educational Resources Information Center

Akande, A.; Osagie, J. E.; Mwaiteleke, P. B.; Botha, K. F. H.; Ababio, E. P.; Selepe, T. J.; Chipeta, K.

1999-01-01

Explores fears and phobias of childhood from a behavioral perspective. Maintains that many childhood fears are mild, age-specific, and transitory, whereas others persist beyond normal developmental limits. Maintains that severe school phobia is difficult to manage. Notes that reports of successful behavioral treatments of fears/phobias are rare in…

Parainflammation, chronic inflammation and age-related macular degeneration

PubMed Central

Chen, Mei; Xu, Heping

2016-01-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study.

PubMed

Miodownik, Chanoch; Lerner, Vladimir; Vishne, Tali; Sela, Ben-Ami; Levine, Joseph

2007-01-01

Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder.

Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo

PubMed Central

Lee, Keunsook K.; MacCallum, Donna M.; Jacobsen, Mette D.; Walker, Louise A.; Odds, Frank C.

2012-01-01

Candida albicans cells with increased cell wall chitin have reduced echinocandin susceptibility in vitro. The aim of this study was to investigate whether C. albicans cells with elevated chitin levels have reduced echinocandin susceptibility in vivo. BALB/c mice were infected with C. albicans cells with normal chitin levels and compared to mice infected with high-chitin cells. Caspofungin therapy was initiated at 24 h postinfection. Mice infected with chitin-normal cells were successfully treated with caspofungin, as indicated by reduced kidney fungal burdens, reduced weight loss, and decreased C. albicans density in kidney lesions. In contrast, mice infected with high-chitin C. albicans cells were less susceptible to caspofungin, as they had higher kidney fungal burdens and greater weight loss during early infection. Cells recovered from mouse kidneys at 24 h postinfection with high-chitin cells had 1.6-fold higher chitin levels than cells from mice infected with chitin-normal cells and maintained a significantly reduced susceptibility to caspofungin when tested in vitro. At 48 h postinfection, caspofungin treatment induced a further increase in chitin content of C. albicans cells harvested from kidneys compared to saline treatment. Some of the recovered clones had acquired, at a low frequency, a point mutation in FKS1 resulting in a S645Y amino acid substitution, a mutation known to confer echinocandin resistance. This occurred even in cells that had not been exposed to caspofungin. Our results suggest that the efficacy of caspofungin against C. albicans was reduced in vivo due to either elevation of chitin levels in the cell wall or acquisition of FKS1 point mutations. PMID:21986821

Plasma progesterone levels and luteal activity during gestation and prolonged oviductal egg retention in a tropical lizard, Calotes versicolor.

PubMed

Shanbhag, B A; Radder, R S; Saidapur, S K

2001-07-01

Plasma progesterone (P) levels and luteal and adrenal activities were studied during normal gestation and unusual prolonged period of oviductal egg retention in a polyautochronic, multiclutched lizard, Calotes versicolor. The normal gestation period (approximately 15 days) was categorized into four stages: stage I--a few hours following ovulation, stage II--eggs with shell and embryo at primitive streak, stage III--embryonic stages 16-20, and stage IV--prior to ovipostion (stages 26-27). The gravid lizards maintained in captivity retained eggs in their oviducts for 45 days. Plasma P levels were low in stage I, increased significantly during stage II, declined in stage III, and reached their lowest in stage IV of gestation. 3Beta-hydroxysteroid dehydrogenase (3beta-HSDH) activity was greater in lutein cells at stage II and was present in traces in stage IV gestation. Interestingly, plasma P titers that were high in lizards with eggs retained longer though the corpora lutea (CL) showed a trace 3beta-HSDH activity. However, 3beta-HSDH activity was greater in the adrenocortical cells in these lizards than that in lizards during a normal gestation period. The present study on C. versicolor shows that the CL remains active and secretes P only during the early part of the gestation. The drop in P level during the later part of gestation might facilitate growth of a second set of vitellogenic follicles. During unfavorable conditions when the lizards are forced to retain eggs in the oviduct, the adrenal glands seem to secrete progesterone to help in egg retention and in inhibition of oviposition.

Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.

PubMed

Desai, Seema S; Tung, Jason C; Zhou, Vivian X; Grenert, James P; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M; Chang, Tammy T

2016-07-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275). © 2016 by the American Association for the Study of Liver Diseases.

Effect of lipid-lowering dietary recommendations on the nutritional intake and lipid profiles of chronic peritoneal dialysis and hemodialysis patients.

PubMed

Saltissi, D; Morgan, C; Knight, B; Chang, W; Rigby, R; Westhuyzen, J

2001-06-01

Patients with end-stage renal failure are a high-risk group for atherosclerotic cardiovascular disease and commonly have dyslipidemia as a major factor. Dietary manipulation is the recommended first line of therapy for reducing lipid levels in people with normal renal function; however, complex dietary requirements of dialysis-treated patients with end-stage renal failure impose significant constraints. In this study, we evaluated the effect of trying to comply with established lipid-lowering recommendations superimposed on our normally prescribed dialysis diet over 14 weeks in stable subjects treated with either hemodialysis (HD) or chronic peritoneal dialysis (PD). Of 306 dialysis patients screened, 75 subjects were enrolled; 8 subjects did not complete the study. In the remainder, HD subjects (n = 41) decreased saturated fat intakes by 18% overall and cholesterol intakes by 16%. This was associated with a decrease in total cholesterol levels from 232 +/- 8 to 209 +/- 4 mg/dL (mean +/- SEM; P = 0.007) and low-density lipoprotein cholesterol levels from 147 +/- 4 to 131 +/- 4 mg/dL (P = 0.009). However, energy intakes decreased by almost 10%. There were no statistically significant changes in PD patients (n = 26). Only 24.4% of HD (10 of 41 patients) and 15.4% of PD patients (4 of 26 patients) normalized their lipid levels. Considerable problems were encountered in maintaining compliance with the modified dialysis diets. This study shows that if adhered to, properly constructed dialysis diets are close to optimal lipid-lowering recommendations. Further dietary manipulation is difficult, leads to little benefit in the majority, and is accompanied by added problems of adherence. We conclude that the vast majority of dyslipidemic patients with end-stage renal failure require pharmacological therapy.

Obesity, change of body mass index and subsequent physical and mental health functioning: a 12-year follow-up study among ageing employees.

PubMed

Svärd, Anna; Lahti, Jouni; Roos, Eira; Rahkonen, Ossi; Lahelma, Eero; Lallukka, Tea; Mänty, Minna

2017-09-26

Studies suggest an association between weight change and subsequent poor physical health functioning, whereas the association with mental health functioning is inconsistent. We aimed to examine whether obesity and change of body mass index among normal weight, overweight and obese women and men associate with changes in physical and mental health functioning. The Helsinki Health Study cohort includes Finnish municipal employees aged 40 to 60 in 2000-02 (phase 1, response rate 67%). Phase 2 mail survey (response rate 82%) took place in 2007 and phase 3 in 2012 (response rate 76%). This study included 5668 participants (82% women). Seven weight change categories were formed based on body mass index (BMI) (phase 1) and weight change (BMI change ≥5%) (phase 1-2). The Short Form 36 Health Survey (SF-36) measured physical and mental health functioning. The change in health functioning (phase 1-3) score was examined with repeated measures analyses. Covariates were age, sociodemographic factors, health behaviours, and somatic ill-health. Weight gain was common among women (34%) and men (25%). Weight-gaining normal weight (-1.3 points), overweight (-1.3 points) and obese (-3.6 points) women showed a greater decline in physical component summary scores than weight-maintaining normal weight women. Among weight-maintainers, only obese (-1.8 points) women showed a greater decline than weight-maintaining normal weight women. The associations were similar, but statistically non-significant for obese men. No statistically significant differences in the change in mental health functioning occurred. Preventing weight gain likely helps maintaining good physical health functioning and work ability.

Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development

PubMed Central

Bratic, Ivana; Hench, Jürgen; Henriksson, Johan; Antebi, Adam; Bürglin, Thomas R; Trifunovic, Aleksandra

2009-01-01

A number of studies showed that the development and the lifespan of Caenorhabditis elegans is dependent on mitochondrial function. In this study, we addressed the role of mitochondrial DNA levels and mtDNA maintenance in development of C. elegans by analyzing deletion mutants for mitochondrial polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in other model organisms showed necessity of polymerase gamma for embryonic development, homozygous polg-1(ok1548) mutants had normal development and reached adulthood without any morphological defects. However, polg-1 deficient animals have a seriously compromised gonadal function as a result of severe mitochondrial depletion, leading to sterility and shortened lifespan. Our results indicate that the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult somatic tissues mainly stems from the developing embryo. Furthermore, we show that the mtDNA copy number shows great plasticity as it can be almost tripled as a response to the environmental stimuli. Finally, we show that the mtDNA copy number is an essential limiting factor for the worm development and therefore, a number of mechanisms set to maintain mtDNA levels exist, ensuring a normal development of C. elegans even in the absence of the mitochondrial replicase. PMID:19181702

[Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

PubMed

Ma, Yi-Ran; Ren, Si-Hua; He, Yu-Xin; Wang, Lin-Lin; Jin, Li; Hao, Yi-Wen

2012-10-01

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.

Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections.

PubMed

Rodrigues-da-Silva, Rodrigo Nunes; Lima-Junior, Josué da Costa; Fonseca, Bruna de Paula Fonseca e; Antas, Paulo Renato Zuquim; Baldez, Arlete; Storer, Fabio Luiz; Santos, Fátima; Banic, Dalma Maria; Oliveira-Ferreira, Joseli de

2014-04-01

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

Men with Low Vitamin A Stores Respond Adequately to Primary Yellow Fever and Secondary Tetanus Toxoid Vaccination12

PubMed Central

Ahmad, Shaikh M.; Haskell, Marjorie J.; Raqib, Rubhana; Stephensen, Charles B.

2008-01-01

Current recommendations for vitamin A intake and liver stores (0.07 μmol/g) are based on maintaining normal vision. Higher levels may be required for maintaining normal immune function. The objective of this study was to assess the relationship between total body vitamin A stores in adult men and measures of adaptive immune function. We conducted an 8-wk residential study among 36 healthy Bangladeshi men with low vitamin A stores. Subjects received a standard diet and were randomized in a double-blind fashion to receive vitamin A (240 mg) or placebo during wk 2 and 3. Subjects received Yellow Fever Virus (YFV) and tetanus toxoid (TT) vaccines during wk 5. Vitamin A stores were estimated by isotopic dilution during wk 8. Vaccine-specific lymphocyte proliferation, cytokine production, and serum antibody responses were evaluated before and after vaccination. Vitamin A supplementation increased YFV- and TT-specific lymphocyte proliferation and YFV-specific interleukin (IL)-5, IL-10, and tumor necrosis factor-α production but inhibited development of a TT-specific IL-10 response. Both groups developed protective antibody responses to both vaccines. Some responses correlated positively with vitamin A stores. These findings indicate that the currently recommended vitamin A intake is sufficient to sustain a protective response to YFV and TT vaccination. However, YFV-specific lymphocyte proliferation, some cytokine responses, and neutralizing antibody were positively associated with liver vitamin A stores > 0.084 μmol/g. Such increases may enhance vaccine protection but raise the question of whether immune-mediated chronic diseases may by exacerbated by high-level dietary vitamin A. PMID:18936231

Expression pattern and function of tyrosine receptor kinase B isoforms in rat mesenteric arterial smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Otani, Kosuke; Okada, Muneyoshi; Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp

Tyrosine receptor kinaseB (TrkB) is a high affinity receptor for brain-derived neurotrophic factor (BDNF). TrkB isoforms involve full length TrkB (TrkB FL) and truncated TrkB type1 (TrkB T1) and type 2 (TrkB T2) in rats. The aim of present study was to explore their expression pattern and function in mesenteric arterial smooth muscle cells (MASMCs). The expression of TrkB isoform protein and mRNA was examined by Western blotting, immunofluorescence and quantitative RT-PCR analyses. Cell proliferation was measured by a bromodeoxyuridine (BrdU) incorporation assay. Cell migration was measured by a Boyden chamber assay. Cell morphology was observed with a phase-contrast microscope.more » Protein and mRNA expression of BDNF and TrkB isoforms was confirmed in MASMCs. Expression level of TrkB FL was less, while that of TrkB T1 was the highest in MASMCs. Although BDNF increased phosphorylation of ERK, it had no influence on migration and proliferation of MASMCs. TrkB T1 gene knockdown by a RNA interference induced morphological changes and reduced expression level of α-smooth muscle actin (α-SMA) in MASMCs. Similar morphological changes and reduced α-SMA expression were induced in MASMCs by a Rho kinase inhibitor, Y-27632. In conclusion, we for the first time demonstrate that TrkB T1 expressed highly in MASMCs contributes to maintain normal cell morphology possibly via regulation of Rho activity. This study firstly defined expression level of TrkB isoforms and partly revealed their functions in peripheral vascular cells. - Highlights: • BDNF-TrkB axis mediates neurogenesis, growth, differentiation and survival. • Expression pattern and function of TrkB in vascular smooth muscle remain unclear. • Expression of TrkB FL is low, while that of TrkB T1 is the highest. • TrkB T1 contributes to maintain normal morphology possibly via activating Rho.« less

Basal p53 expression is indispensable for mesenchymal stem cell integrity.

PubMed

Boregowda, Siddaraju V; Krishnappa, Veena; Strivelli, Jacqueline; Haga, Christopher L; Booker, Cori N; Phinney, Donald G

2018-03-01

Marrow-resident mesenchymal stem cells (MSCs) serve as a functional component of the perivascular niche that regulates hematopoiesis. They also represent the main source of bone formed in adult bone marrow, and their bifurcation to osteoblast and adipocyte lineages plays a key role in skeletal homeostasis and aging. Although the tumor suppressor p53 also functions in bone organogenesis, homeostasis, and neoplasia, its role in MSCs remains poorly described. Herein, we examined the normal physiological role of p53 in primary MSCs cultured under physiologic oxygen levels. Using knockout mice and gene silencing we show that p53 inactivation downregulates expression of TWIST2, which normally restrains cellular differentiation to maintain wild-type MSCs in a multipotent state, depletes mitochondrial reactive oxygen species (ROS) levels, and suppresses ROS generation and PPARG gene and protein induction in response to adipogenic stimuli. Mechanistically, this loss of adipogenic potential skews MSCs toward an osteogenic fate, which is further potentiated by TWIST2 downregulation, resulting in highly augmented osteogenic differentiation. We also show that p53 - /- MSCs are defective in supporting hematopoiesis as measured in standard colony assays because of decreased secretion of various cytokines including CXCL12 and CSF1. Lastly, we show that transient exposure of wild-type MSCs to 21% oxygen upregulates p53 protein expression, resulting in increased mitochondrial ROS production and enhanced adipogenic differentiation at the expense of osteogenesis, and that treatment of cells with FGF2 mitigates these effects by inducing TWIST2. Together, these findings indicate that basal p53 levels are necessary to maintain MSC bi-potency, and oxygen-induced increases in p53 expression modulate cell fate and survival decisions. Because of the critical function of basal p53 in MSCs, our findings question the use of p53 null cell lines as MSC surrogates, and also implicate dysfunctional MSC responses in the pathophysiology of p53-related skeletal disorders.

Characterization of the electrical output of flat-plate photovoltaic arrays

NASA Technical Reports Server (NTRS)

Gonzalez, C. C.; Hill, G. M.; Ross, R. G., Jr.

1982-01-01

The electric output of flat-plate photovoltaic arrays changes constantly, due primarily to changes in cell temperature and irradiance level. As a result, array loads such as direct-current to alternating-current power conditioners must be able to accommodate widely varying input levels, while maintaining operation at or near the array maximum power point.The results of an extensive computer simulation study that was used to define the parameters necessary for the systematic design of array/power-conditioner interfaces are presented as normalized ratios of power-conditioner parameters to array parameters, to make the results universally applicable to a wide variety of system sizes, sites, and operating modes. The advantages of maximum power tracking and a technique for computing average annual power-conditioner efficiency are discussed.

Experiment K-6-16. Morphological examination of rat testes. The effect of Cosmos 1887 flight on spermatogonial population and testosterone level in rat testes

NASA Technical Reports Server (NTRS)

Philpott, D. E.; Kato, K.; Stevenson, J.; Vasques, M.; Sapp, W.; Williams, C.; Popova, I. A.; Serova, L. V.

1990-01-01

Testes from rats flown on Cosmos 1887 for twelve and a half days were compared to basal control, synchronous control and vivarium maintained rats. When the mean weights of flight testes, normalized for weight/100 gms, were compared to the vivarium controls they were 6.7 percent lighter. Although the flight testes were lighter than the synchronous, the difference is not significant. Counts of spermatogonial cells from 5 animals in each group revealed a 4 percent decrease in flight compared to vivarium controls. In both cases the t-Test significance was less than 0.02. The serum testosterone levels of all animals (flight, synchronous and vivarium) were significantly below the basal controls.

Metabolic studies with NMR spectroscopy of the alga Dunaliella salina trapped within agarose beads.

PubMed

Bental, M; Pick, U; Avron, M; Degani, H

1990-02-22

A technique for the entrapment of the unicellular algae Dunaliella salina in agarose beads and their perfusion during NMR measurements is presented. The trapped cells maintained their ability to proliferate under normal growth conditions, and remained viable and stable under steady-state conditions for long periods during NMR measurements. Following osmotic shock in the dark, prominent changes were observed in the intracellular level of ATP and polyphosphates, but little to no changes in the intracellular pH or orthoposphate content. When cells were subjected to hyperosmotic shock, the ATP level decreased. The content of NMR-visible polyphosphates decreased as well, presumably due to the production of longer, NMR-invisible structures. Following hypoosmotic shock, the ATP content increased and longer polyphosphates were broken down to shorter, more mobile polymers.

Chemopreventive effect of bacoside A on N-nitrosodiethylamine-induced hepatocarcinogenesis in rats.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Ravisankar, Baskaran; Parthasarathy, Chandrakesan

2010-05-01

Chemoprevention is an effective approach to control hepatocarcinogenesis. Bacoside A, the active constituent of Bacopa monniera Linn., is anticipated to play a role in chemoprevention of liver cancer. In the present study, we investigated the chemopreventive effect of bacoside A against N-nitrosodiethylamine-induced hepatocarcinogenesis in an animal model. Administration of carcinogen showed a significant elevation in the levels of lipid peroxidation, serum tumor marker enzymes and liver injury marker enzymes with subsequent decrease in the levels of both hemolysate and liver antioxidant status. Bacoside A co-treatment maintained the N-nitrosodiethylamine-induced alterations at near normal level. Histopathological and electron microscopic study of the liver tissue also supports the above biochemical observations. From our findings we conclude that bacoside A is effective to prevent DEN-induced hepatocellular carcinoma by quenching lipid peroxidation and enhancing antioxidant status through free radical scavenging mechanism and having potential of protecting endogenous enzymatic and non-enzymatic antioxidant activity.

A systems model for immune cell interactions unravels the mechanism of inflammation in human skin.

PubMed

Valeyev, Najl V; Hundhausen, Christian; Umezawa, Yoshinori; Kotov, Nikolay V; Williams, Gareth; Clop, Alex; Ainali, Crysanthi; Ouzounis, Christos; Tsoka, Sophia; Nestle, Frank O

2010-12-02

Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes.

Obesity and Sexuality Among Older Couples.

PubMed

Kwon, Soyoung; Schafer, Markus H

2016-04-01

We investigate whether obesity is associated with sexual activity, sexual frequency, and the range of sexual behaviors in heterosexual older couples. We assess to what extent associations between obesity and sexuality are explained by physical, psychological, and sexual health, and by relationship quality. We use data from 1,698 older adults in 849 partnered dyads in the 2010-2011 wave of the National Social Life, Health, and Aging Project and conduct couple-level analysis featuring women's and men's characteristics. Women's obesity-particularly at severe levels-is negatively associated with coupled sexual activity, and that the association is not mediated by hypothesized mediators. Men's obesity did not have any association with sexual activity. There was no significant difference between overweight and normal weight adults across all three sexuality measures. The growing number of older adults with high levels of body mass index, particularly women, may face certain difficulties in maintaining active sexual lives.

GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

PubMed

Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

2016-01-01

Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice.

Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

PubMed

Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

2011-08-01

To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Relationship between seminal plasma levels of anandamide congeners palmitoylethanolamide and oleoylethanolamide and semen quality.

PubMed

Amoako, Akwasi Atakora; Marczylo, Timothy Hywel; Elson, Janine; Taylor, Anthony Henry; Willets, Jonathon M; Konje, Justin Chi

2014-11-01

To determine whether changes in seminal plasma concentrations of the endogenous lipid signaling molecules palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) have significant effects on sperm quality. Biochemical and physiological studies of human seminal plasma and spermatozoa. Academic tertiary care medical center. Ninety men attending an infertility clinic for semen analysis. Palmitoylethanolamide and OEA extracted from seminal plasma were quantified by ultra high-performance liquid chromatography (HPLC)-tandem mass spectrometry. Patient sperm from semen with normal parameters were exposed in vitro to PEA or OEA to determine effects on sperm motility, viability, and mitochondrial activity. The relationship between seminal plasma concentrations of PEA and OEA and sperm quality and the effect of these compounds on sperm motility, viability, and mitochondria activity in vitro. Palmitoylethanolamide and OEA concentrations in seminal plasma were lower in men with asthenozoospermia and oligoasthenoteratozospermia compared with men with normal semen parameters. Palmitoylethanolamide and OEA rapidly and significantly improved sperm motility and maintained viability without affecting mitochondria activity in vitro. Maintenance of normal PEA and OEA tone in human seminal plasma may be necessary for the preservation of normal sperm function and male fertility. Exocannabinoids found in Cannabis, such as delta-9-tetrahydrocannabinol and cannabidiol, could compete with these endocannabinoids upsetting their finely balanced, normal functioning and resulting in male reproductive failure. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Loss of end-differentiated β-cell phenotype following pancreatic islet transplantation.

PubMed

Anderson, S J; White, M G; Armour, S L; Maheshwari, R; Tiniakos, D; Muller, Y D; Berishvili, E; Berney, T; Shaw, J A M

2018-03-01

Replacement of pancreatic β-cells through deceased donor islet transplantation is a proven therapy for preventing recurrent life-threatening hypoglycemia in type 1 diabetes. Although near-normal glucose levels and insulin independence can be maintained for many years following successful islet transplantation, restoration of normal functional β-cell mass has remained elusive. It has recently been proposed that dedifferentiation/plasticity towards other endocrine phenotypes may play an important role in stress-induced β-cell dysfunction in type 2 diabetes. Here we report loss of end-differentiated β-cell phenotype in 2 intraportal islet allotransplant recipients. Despite excellent graft function and sustained insulin independence, all examined insulin-positive cells had lost expression of the end-differentiation marker, urocortin-3, or appeared to co-express the α-cell marker, glucagon. In contrast, no insulin + /urocortin-3 - cells were seen in nondiabetic deceased donor control pancreatic islets. Loss of end-differentiated phenotype may facilitate β-cell survival during the stresses associated with islet isolation and culture, in addition to sustained hypoxia following engraftment. As further refinements in islet isolation and culture are made in parallel with exploration of alternative β-cell sources, graft sites, and ultimately fully vascularized bioengineered insulin-secreting microtissues, differentiation status immunostaining provides a novel tool to assess whether fully mature β-cell phenotype has been maintained. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection

PubMed Central

Goodwin, Thomas J.; McCarthy, Maureen; Osterrieder, Nikolaus; Cohrs, Randall J.; Kaufer, Benedikt B.

2013-01-01

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells. PMID:23935496

3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.

2013-01-01

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

The character of sleep disturbances produced by multiple administrations of atropine the antagonist of brain muscarinic cholinergic system.

PubMed

Maglakelidze, N T; Chkhartishvili, E V; Mchedlidze, O M; Dzadzamiia, Sh Sh; Nachkebiia, N G

2012-03-01

Modification of brain muscarinic cholinergic system normal functioning can be considered as an appropriate strategy for the study of its role in sleep-wakefulness cycle basic mechanisms in general and in the course/maintenance of PS in particular. For this aim systemic application of muscarinic cholinoreceptors antagonists is significant because it gives possibility to modify functioning all of known five sub-types of muscarinic cholinoreceptors and to study the character of sleep disturbances in these conditions. Problem is very topical because the question about the intimate aspects of BMChS involvement in PS maintaining mechanisms still remains unsolved. In cats Atropine systemic administration was made once daily at 10:00 a.m. and continuous EEG registration of sleep-wakefulness cycle ultradian structure, lasting for 10 hour daily, was started immediately. In sum each animal received anti-muscarinic drugs for 12 times. Thereafter drug administrations were ceased and EEG registration of sleep-wakefulness cycle ultradian structure was continued during 10 consecutive days. On the basis of results obtained in these conditions we can conclude that brain muscarinic cholinergic system normal functioning is significant for basic mechanisms of sleep-wakefulness cycle. During wakefulness, at the level of neocortex and hippocampus, MChS supports only EEG activation, while it is one of the main factors in PS triggering and maintaining mechanisms.

Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10

PubMed Central

Xie, Luokun; Choudhury, Gourav Roy; Winters, Ali; Yang, Shao-Hua; Jin, Kunlin

2014-01-01

Forkhead box P3 (Foxp3)+ regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the central nervous system under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ+CD4+Foxp3+ T-cell population (cerebral Treg cells) in the normal rat cerebrum, constituting more than 15% of the cerebral CD4+ T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the normal rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state. PMID:25329858

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

PubMed Central

Dalgin, Gökhan; Prince, Victoria E.

2015-01-01

During development a network of transcription factors functions to differentiate foregut cells into pancreatic endocrine cells. Differentiation of appropriate numbers of each hormone-expressing endocrine cell type is essential for the normal development of the pancreas and ultimately for effective maintenance of blood glucose levels. A fuller understanding of the details of endocrine cell differentiation may contribute to development of cell replacement therapies to treat diabetes. In this study, by using morpholino and gRNA/Cas9 mediated knockdown we establish that differential levels of the basic-helix loop helix (bHLH) transcription factor Neurod are required for the differentiation of distinct endocrine cell types in developing zebrafish. While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-expressing beta cells is less sensitive to Neurod depletion. The endocrine cells that arise during embryonic stages to produce the primary islet, and those that arise subsequently during larval stages from the intra-pancreatic duct (IPD) to ultimately contribute to the secondary islets, show similar dependence on differential Neurod levels. Intriguingly, Neurod-deficiency triggers premature formation of endocrine precursors from the IPD during early larval stages. However, the Neurod-deficient endocrine precursors fail to differentiate appropriately, and the larvae are unable to maintain normal glucose levels. In summary, differential levels of Neurod are required to generate endocrine pancreas subtypes from precursors during both embryonic and larval stages, and Neurod function is in turn critical to endocrine function. PMID:25797153

Normal Postprandial Nonesterified Fatty Acid Uptake in Muscles Despite Increased Circulating Fatty Acids in Type 2 Diabetes

PubMed Central

Labbé, Sébastien M.; Croteau, Etienne; Grenier-Larouche, Thomas; Frisch, Frédérique; Ouellet, René; Langlois, Réjean; Guérin, Brigitte; Turcotte, Eric E.; Carpentier, André C.

2011-01-01

OBJECTIVE Postprandial plasma nonesterified fatty acid (NEFA) appearance is increased in type 2 diabetes. Our objective was to determine whether skeletal muscle uptake of plasma NEFA is abnormal during the postprandial state in type 2 diabetes. RESEARCH DESIGN AND METHODS Thigh muscle blood flow and oxidative metabolism indexes and NEFA uptake were determined using positron emission tomography coupled with computed tomography (PET/CT) with [11C]acetate and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18FTHA) in seven healthy control subjects (CON) and seven subjects with type 2 diabetes during continuous oral intake of a liquid meal to achieve steady postprandial NEFA levels with insulin infusion to maintain similar plasma glucose levels in both groups. RESULTS In the postprandial state, plasma NEFA level was higher in type 2 diabetic subjects versus CON (P < 0.01), whereas plasma glucose was at the same level in both groups. Muscle NEFA fractional extraction and blood flow index levels were 56% (P < 0.05) and 24% (P = 0.27) lower in type 2 diabetes, respectively. However, muscle NEFA uptake was similar to that of CON (quadriceps femoris [QF] 1.47 ± 0.23 vs. 1.37 ± 0.24 nmol ⋅ g−1 ⋅ min−1, P = 0.77; biceps femoris [BF] 1.54 ± 0.26 vs. 1.46 ± 0.28 nmol ⋅ g−1 ⋅ min−1, P = 0.85). Muscle oxidative metabolism was similar in both groups. Muscle NEFA fractional extraction and blood flow index were strongly and positively correlated (r = 0.79, P < 0.005). CONCLUSIONS Postprandial muscle NEFA uptake is normal despite elevated systemic NEFA levels and acute normalization of plasma glucose in type 2 diabetes. Lower postprandial muscle blood flow with resulting reduction in muscle NEFA fractional extraction may explain this phenomenon. PMID:21228312

The influence of the platelet count on the incidence of thrombotic and haemorrhagic complications in polycythaemia vera

PubMed Central

Dawson, Audrey A.; Ogston, D.

1970-01-01

In polycythaemia vera, those patients who have an elevated platelet count develop more thrombotic and more haemorrhagic complications than those with a normal count, even when the haematocrit is maintained by therapy within the normal range. PMID:5416508

Effects of petroleum on adrenocortical activity and on hepatic naphthalene-metabolizing activity in mallard ducks

USGS Publications Warehouse

Gorsline, J.; Holmes, W.N.

1981-01-01

Unstressed mallard ducks (Anas platyrhychos), given uncontaminated food and maintained on a short photoperiod, show two daily maxima in plasma corticosterone concentration ([B]); one occurring early in the light phase and a second just before the onset of darkness. After one week of exposure to food containing 3% (v/w) South Louisiana crude oil, plasma [B] were significantly lowered throughout the day. Similar abrupt declines in plasma [B] also occurred during the first 10 days of exposure to food containing 1% and 0.5% crude oil. Although the plasma [B] in birds consuming food contaminated with 0.5% crude oil increased between 10 and 50 days of exposure, the concentration after 50 days was still lower than normal. During the same interval, normal plasma [B] were restored in birds consuming food containing 1% and 3% crude oil. Significant increases occurred in the naphthalene-metabolizing properties of hepatic microsomes prepared from birds acutely exposed to all levels of petroleum-contaminated food and elevated levels were sustained throughout the first 50 days of exposure. Birds given food containing 3% crude oil for more than 50 days, however, showed steady declines in hepatic naphthalene-metabolizing activity. After 500 days, the activity was similar to that found in contemporaneous controls. During the same interval, the plasma [B] increased until the levels were higher than normal after 500 days of exposure; at this time, an inverse relationship, similar to that seen during the first week of exposure to contaminated food, was once more established between plasma [B] and the concomitant hepatic naphthalene-metabolizing activity.

Reduction of systemic exposure and toxicity of cisplatin by encapsulation in poly-lactide-co-glycolide.

PubMed

Verrijk, R; Smolders, I J; Bosnie, N; Begg, A C

1992-12-01

The tissue distribution and normal tissue toxicity of cisplatin (cDDP) administered as poly-lactide-co-glycolide (PLAGA) microspheres, developed for loco-regional administration of cDDP to the liver, were studied in Wag/Rij rats. Venoportal administration of this formulation resulted in a reduction in total systemic and renal toxicity, which correlated with a decrease in normal tissue exposure to cDDP while maintaining high liver platinum levels. Liver-to-kidney platinum level ratios were 28 times higher after 4 h and 19 times higher after 24 h with PLAGA-cDDP microspheres than with free cDDP. Liver-to-blood platinum ratios at these times were 38 times and 36 times higher using PLAGA-cDDP. In a CC531 colon carcinoma liver micrometastases model, cytotoxicity of microsphere-released cDDP was confirmed in vivo by equal inhibition of tumor growth by PLAGA-cDDP and free cDDP over a period of 26 days. Free cDDP, however, caused significantly more histological renal damage and total body weight loss. The results were supported by the finding of higher plasma creatinine and urea concentrations 26 days after administration of free cDDP. Kidney platinum levels were 7 times lower when PLAGA-cDDP was used. These findings indicate a sparing effect on normal tissues when cDDP is targeted to the liver by formulation in PLAGA. PLAGA-cDDP microspheres may, therefore, be a useful and effective addition to current techniques of loco-regional chemotherapy for disseminated hepatic tumors.

Adenosine A2A receptor inhibition restores the normal transport of endothelial glutamate transporters in the brain.

PubMed

Bai, Wei; Li, Ping; Ning, Ya-Lei; Peng, Yan; Xiong, Ren-Ping; Yang, Nan; Chen, Xing; Zhou, Yuan-Guo

2018-04-15

Excitatory amino acid transporters (EAATs) on cerebral vascular endothelial cells play an important role in maintaining glutamate homeostasis in the brain. The dysfunction of endothelial EAATs is an important reason for the dramatically elevated brain glutamate levels after brain injury, such as traumatic brain injury (TBI). The adenosine A 2A receptor (A 2A R) plays an important role in regulating the brain glutamate level after brain injury; however, researchers have not clearly determined whether this role was related to its ability to regulate endothelial EAATs. Activation of A 2A R in vitro not only decreased the PKA- and glutamate level-dependent strengthening of the interaction between NKA-α1 and the FXYD1 subunit and the subsequent decrease in the activity of Na + /K + -ATPases (NKAs) but also enhanced its interaction with EAATs and ultimately aggravated the reverse transport function of endothelial EAATs under oxygen-glucose deprivation (OGD) conditions. Conversely, inhibition of A 2A R restored the normal transport of EAAT. Moreover, A 2A R inhibition increased NKA activity and decreased its interaction with EAATs in isolated brain capillaries after TBI, further confirming its role in endothelial EAATs in vivo. Based on our results, A 2A R played an important role in regulating endothelial EAAT function, and strategies that restore the normal transport of endothelial EAATs through the inhibition of A 2A R might serve as an effective treatment for brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Knock-Limited Performance of Triptane and Xylidines Blended with 28-R Aviation Fuel at High Compression Ratios and Maximum-Economy Spark Setting

NASA Technical Reports Server (NTRS)

Held, Louis F.; Pritchard, Ernest I.

1946-01-01

An investigation was conducted to evaluate the possibilities of utilizing the high-performance characteristics of triptane and xylidines blended with 28-R fuel in order to increase fuel economy by the use of high compression ratios and maximum-economy spark setting. Full-scale single-cylinder knock tests were run with 20 deg B.T.C. and maximum-economy spark settings at compression ratios of 6.9, 8.0, and 10.0, and with two inlet-air temperatures. The fuels tested consisted of triptane, four triptane and one xylidines blend with 28-R, and 28-R fuel alone. Indicated specific fuel consumption at lean mixtures was decreased approximately 17 percent at a compression ratio of 10.0 and maximum-economy spark setting, as compared to that obtained with a compression ratio of 6.9 and normal spark setting. When compression ratio was increased from 6.9 to 10.0 at an inlet-air temperature of 150 F, normal spark setting, and a fuel-air ratio of 0.065, 55-percent triptane was required with 28-R fuel to maintain the knock-limited brake power level obtained with 28-R fuel at a compression ratio of 6.9. Brake specific fuel consumption was decreased 17.5 percent at a compression ratio of 10.0 relative to that obtained at a compression ratio of 6.9. Approximately similar results were noted at an inlet-air temperature of 250 F. For concentrations up through at least 20 percent, triptane can be more efficiently used at normal than at maximum-economy spark setting to maintain a constant knock-limited power output over the range of compression ratios tested.

Control of body temperature and immune function in patients undergoing open surgery for gastric cancer.

PubMed

Shao, Li; Pang, Nannan; Yan, Ping; Jia, Fengju; Sun, Qi; Ma, Wenjuan; Yang, Yi

2018-04-09

The influence of mild perioperative hypothermia on the immune function and incidence of postoperative wound infections has been suggested, but the specific mechanism is unclear. This study aimed to analyze the body temperature, immune function, and wound infection rates in patients receiving open surgery for gastric cancer. Body temperature was controlled in each patient using one of four different methods: wrapping limbs, head and neck; insulated blankets; warming infusion fluids and insulated blankets; and warming fluids without insulated blankets. One hundred patients were randomly divided into four groups of 25 patients each, and every group received a different intraoperative treatment for maintaining normal body temperature. Nasopharyngeal and rectal temperatures, transforming growth factor beta (TGF-β), interleukin 10 (IL-10) levels, and cluster of differentiation (CD)3+ and CD4+/CD25+ regulatory T cell (Treg) counts were measured before surgery and at 2 and 4 hours postoperatively. Patients were evaluated at one week after surgery for signs of infection. Intraoperative body temperature and measures of immune function varied significantly between the four groups, with the largest temperature changes observed in the group in which only the limbs were wrapped in cotton pads to control the body temperature. The group in which infusion fluids and transfused blood (if needed) were heated to 37℃, peritoneal irrigation fluid was heated to 37℃, and an insulation blanket was heated to 39℃ and placed under the patient, showed the lowest temperature change (i.e., close to normal temperature) and cytokine response after surgery. No intergroup differences were found in the infection rates at one week after surgery. In conclusion, body temperature variation during surgery affects the immune function of patients, and maintaining body temperature close to normal results in the least variation of immune function.

Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

PubMed Central

Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

2015-01-01

Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

An extra-uterine system to physiologically support the extreme premature lamb

PubMed Central

Partridge, Emily A.; Davey, Marcus G.; Hornick, Matthew A.; McGovern, Patrick E.; Mejaddam, Ali Y.; Vrecenak, Jesse D.; Mesas-Burgos, Carmen; Olive, Aliza; Caskey, Robert C.; Weiland, Theodore R.; Han, Jiancheng; Schupper, Alexander J.; Connelly, James T.; Dysart, Kevin C.; Rychik, Jack; Hedrick, Holly L.; Peranteau, William H.; Flake, Alan W.

2017-01-01

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed ‘amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination. PMID:28440792

An extra-uterine system to physiologically support the extreme premature lamb

NASA Astrophysics Data System (ADS)

Partridge, Emily A.; Davey, Marcus G.; Hornick, Matthew A.; McGovern, Patrick E.; Mejaddam, Ali Y.; Vrecenak, Jesse D.; Mesas-Burgos, Carmen; Olive, Aliza; Caskey, Robert C.; Weiland, Theodore R.; Han, Jiancheng; Schupper, Alexander J.; Connelly, James T.; Dysart, Kevin C.; Rychik, Jack; Hedrick, Holly L.; Peranteau, William H.; Flake, Alan W.

2017-04-01

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed `amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.

7 CFR 760.204 - Eligible livestock, honeybees, and farm-raised fish.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., goats, llamas, poultry, reindeer, sheep, or swine; (2) Be livestock that would normally have been... livestock that has been maintained for commercial use as part of the producer's farming operation on the... been produced and maintained for reasons other than commercial use as part of a farming operation; and...

Impaired detection of happy facial expressions in autism.

PubMed

Sato, Wataru; Sawada, Reiko; Uono, Shota; Yoshimura, Sayaka; Kochiyama, Takanori; Kubota, Yasutaka; Sakihama, Morimitsu; Toichi, Motomi

2017-10-17

The detection of emotional facial expressions plays an indispensable role in social interaction. Psychological studies have shown that typically developing (TD) individuals more rapidly detect emotional expressions than neutral expressions. However, it remains unclear whether individuals with autistic phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic traits (ATs), are impaired in this ability. We examined this by comparing TD and ASD individuals in Experiment 1 and individuals with low and high ATs in Experiment 2 using the visual search paradigm. Participants detected normal facial expressions of anger and happiness and their anti-expressions within crowds of neutral expressions. In Experiment 1, reaction times were shorter for normal angry expressions than for anti-expressions in both TD and ASD groups. This was also the case for normal happy expressions vs. anti-expressions in the TD group but not in the ASD group. Similarly, in Experiment 2, the detection of normal vs. anti-expressions was faster for angry expressions in both groups and for happy expressions in the low, but not high, ATs group. These results suggest that the detection of happy facial expressions is impaired in individuals with ASD and high ATs, which may contribute to their difficulty in creating and maintaining affiliative social relationships.

Diminished hepatic growth hormone receptor binding in sex-linked dwarf broiler and leghorn chickens.

PubMed

Leung, F C; Styles, W J; Rosenblum, C I; Lilburn, M S; Marsh, J A

1987-02-01

Hepatic growth hormone (GH) receptor binding was compared in normal and sex-linked dwarfs (SLD) from both Hubbard and Cornell strain chickens. At 6, 8, and 20 weeks of age, hepatic GH receptor binding in the Hubbard SLD chickens was significantly lower than that of normal fast-growing birds. At 20 weeks of age, only 2 of 22 SLD chickens in the Hubbard broiler strain showed positive binding at a high enough level to allow for Scatchard analysis. The affinity constants and binding capacities of these two SLD chickens were numerically (but not significantly) lower than those of the normal fast-growing birds. We further examined hepatic GH receptor binding in two closely related White Leghorn strains of chickens that have been maintained as closed breeding populations for many years. We observed no detectable hepatic GH binding in the Cornell SLD chickens (N = 20), as compared to the normal-growing control strain (K strain). In both SLD strains, pretreatment with 4 M MgCl2 did not enhance GH binding, suggesting that there was no endogenous GH binding to the receptor. Based on these data, we suggest that the lack, or greatly reduced number, of GH receptors may be a major contributing factor to the dwarfism observed in these strains.

Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

PubMed Central

Lieben, Liesbet; Masuyama, Ritsuko; Torrekens, Sophie; Van Looveren, Riet; Schrooten, Jan; Baatsen, Pieter; Lafage-Proust, Marie-Hélène; Dresselaers, Tom; Feng, Jian Q.; Bonewald, Lynda F.; Meyer, Mark B.; Pike, J. Wesley; Bouillon, Roger; Carmeliet, Geert

2012-01-01

Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25(OH)2D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25(OH)2D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25(OH)2D not only increases calcium release from bone, but also inhibits calcium incorporation in bone. PMID:22523068

14 CFR 23.233 - Directional stability and control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... landings at normal landing speed, without using brakes or engine power to maintain a straight path until the speed has decreased to at least 50 percent of the speed at touchdown. (c) The airplane must have... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Ground...

14 CFR 23.233 - Directional stability and control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... landings at normal landing speed, without using brakes or engine power to maintain a straight path until the speed has decreased to at least 50 percent of the speed at touchdown. (c) The airplane must have... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Ground...

14 CFR 23.233 - Directional stability and control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... landings at normal landing speed, without using brakes or engine power to maintain a straight path until the speed has decreased to at least 50 percent of the speed at touchdown. (c) The airplane must have... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Ground...

14 CFR 23.233 - Directional stability and control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... landings at normal landing speed, without using brakes or engine power to maintain a straight path until the speed has decreased to at least 50 percent of the speed at touchdown. (c) The airplane must have... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Ground...

14 CFR 23.233 - Directional stability and control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... landings at normal landing speed, without using brakes or engine power to maintain a straight path until the speed has decreased to at least 50 percent of the speed at touchdown. (c) The airplane must have... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Ground...

Creatine maintains intestinal homeostasis and protects against colitis.

PubMed

Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

2017-02-14

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

Creatine maintains intestinal homeostasis and protects against colitis

PubMed Central

Turer, Emre; McAlpine, William; Wang, Kuan-wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R.; Beutler, Bruce

2017-01-01

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea–mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted (Gatmc/c) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatmc/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatmc/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury. PMID:28137860

Process control of laser conduction welding by thermal imaging measurement with a color camera.

PubMed

Bardin, Fabrice; Morgan, Stephen; Williams, Stewart; McBride, Roy; Moore, Andrew J; Jones, Julian D C; Hand, Duncan P

2005-11-10

Conduction welding offers an alternative to keyhole welding. Compared with keyhole welding, it is an intrinsically stable process because vaporization phenomena are minimal. However, as with keyhole welding, an on-line process-monitoring system is advantageous for quality assurance to maintain the required penetration depth, which in conduction welding is more sensitive to changes in heat sinking. The maximum penetration is obtained when the surface temperature is just below the boiling point, and so we normally wish to maintain the temperature at this level. We describe a two-color optical system that we have developed for real-time temperature profile measurement of the conduction weld pool. The key feature of the system is the use of a complementary metal-oxide semiconductor standard color camera leading to a simplified low-cost optical setup. We present and discuss the real-time temperature measurement and control performance of the system when a defocused beam from a high power Nd:YAG laser is used on 5 mm thick stainless steel workpieces.

Abiotic Stress Tolerance in Plants: Myriad Roles of Ascorbate Peroxidase

PubMed Central

Pandey, Saurabh; Fartyal, Dhirendra; Agarwal, Aakrati; Shukla, Tushita; James, Donald; Kaul, Tanushri; Negi, Yogesh K.; Arora, Sandeep; Reddy, Malireddy K.

2017-01-01

One of the most significant manifestations of environmental stress in plants is the increased production of Reactive Oxygen Species (ROS). These ROS, if allowed to accumulate unchecked, can lead to cellular toxicity. A battery of antioxidant molecules is present in plants for keeping ROS levels under check and to maintain the cellular homeostasis under stress. Ascorbate peroxidase (APX) is a key antioxidant enzyme of such scavenging systems. It catalyses the conversion of H2O2 into H2O, employing ascorbate as an electron donor. The expression of APX is differentially regulated in response to environmental stresses and during normal plant growth and development as well. Different isoforms of APX show differential response to environmental stresses, depending upon their sub-cellular localization, and the presence of specific regulatory elements in the upstream regions of the respective genes. The present review delineates role of APX isoforms with respect to different types of abiotic stresses and its importance as a key antioxidant enzyme in maintaining cellular homeostasis. PMID:28473838

Case of ovarian hyperstimulation and oocyte pick-up during very early period of unnoticed pregnancy followed by ongoing normal pregnancy.

PubMed

Takenaka, Hiroshi; Nakao, Kazuki; Horikawa, Michiharu; Negishi, Hiroaki

2016-04-01

We report a case of unnoticed pregnancy that was maintained during low estrogen and progesterone circumstances, that showed menses-like bleeding, and was then discovered after ovarian hyperstimulation during the next period. The patient was 39 years old and primigravid. She underwent intrauterine insemination, followed by luteal support with human chorionic gonadotrophin and progestin; however, she experienced menstruation-like bleeding 15 days later. As low estradiol and progesterone levels were confirmed on the 2nd day of bleeding, ovarian hyperstimulation of short protocol for in vitro fertilization was commenced. Although 13 mature follicles were observed, only six oocytes were retrieved and one developed into a blastocyst. Four days after oocyte pick-up, a gestational sac was seen in utero. The fetus is currently growing uneventfully. This case suggests that pregnancy can be maintained during ovarian hyperstimulation, even if menstruation-like bleeding is shown in low-progesterone circumstances. © 2016 Japan Society of Obstetrics and Gynecology.

Host-Microbe Interactions in Microgravity: Assessment and Implications

PubMed Central

Foster, Jamie S.; Wheeler, Raymond M.; Pamphile, Regine

2014-01-01

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes. PMID:25370197

Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

PubMed

Mody, Nimesh

2017-11-01

Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

Host-microbe interactions in microgravity: assessment and implications.

PubMed

Foster, Jamie S; Wheeler, Raymond M; Pamphile, Regine

2014-05-26

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes.

Synaptic mechanisms underlying persistent cocaine craving

PubMed Central

Wolf, Marina E.

2017-01-01

Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

Hypothalamic control of energy and glucose metabolism.

PubMed

Sisley, Stephanie; Sandoval, Darleen

2011-09-01

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

Managing Hyperkalemia: Stepping Into a New Frontier.

PubMed

Pham, Antony Q; Sexton, Jessica; Wimer, Dexter; Rana, Isha; Nguyen, Timothy

2017-10-01

Maintaining potassium balance in the body is essential for cellular function. Even a slight increase in normal serum potassium levels (3.5-5.0 mEq/L) can interfere with metabolism, electrical action potentials, and cellular processes. Hyperkalemia is commonly seen in patients with chronic kidney disease (CKD) and in patients on renin-angiotensin-aldosterone system (RAAS) inhibitors. Sodium polystyrene sulfonate (SPS), diuretics, and hemodialysis are currently available methods for removing potassium from the body; however, these options have their limitations. Patiromer (Veltassa) and sodium zirconium cyclosilicate are 2 new therapeutic options that can potentially lead a new frontier in the management of hyperkalemia. This article will review these novel treatments.

Morphological effects of chronic bilateral phrenectomy or vagotomy in the fetal lamb lung.

PubMed Central

Alcorn, D; Adamson, T M; Maloney, J E; Robinson, P M

1980-01-01

The relationship between fetal espiratory activity and fetal lung development has been studied at the cellular level using two experimental models. Chronic bilateral phrenectomy over a period of 20-28 days during the last trimester of the fetal lamb resulted in hypoplastic lungs, although cellular maturity, as indicated by the presence of alveolar epithelial Type II cells, was present. In the lungs from fetal lambs undergoing sham operations for a similar time course there was evidence of enhanced alveolar proliferation when compared with lungs from normal fetal sheep of a similar gastational age, most probably as a result of operative stress. Following chronic bilateral vagotomy no changes in size or histology of the fetal lamb lungs were detected. At an ultrastructural level, however, inclusions of Type II cells consistently showed the loss of the typical osmiophilic lamellated appearance. These results indicate the importance of the fetal breathing apparatus in maintaining a volume of lung liquid which is adequate for normal pulmonary development, particularly during the phase in which alveoli are formed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:7429961

Endometrial estrogen and progesterone receptors within 2-14 days of missed menses in the human.

PubMed

Garg, K; Sujata, P; Kumari, G L; Pandey, P K; Padubidri, V; Anand, C

1993-04-01

Serial changes in the endometrial levels of estrogen and progesterone receptors (ER and PR) were measured in 50 women from days 2 to 14 of missed menses and correlated with the plasma concentrations of hCG, progesterone and 17 beta-estradiol. Both ER and PR of nuclei were higher than cytosolic proteins, with a shift in the ratio of nER/nPR to nPR from 4th day after missed menses. On Scatchard analysis of the cytosolic and nuclear binding proteins, two classes of proteins, corresponding to Type I and II, were found. While the increasing levels of hCG maintained luteal secretion of progesterone and 17 beta-estradiol at normal mid-luteal phase levels, a gradual increase in 17 beta estradiol from 9th day of missed menses was noted. This delicate balance between circulating levels of progesterone and 17 beta-estradiol and their nuclear receptors at early stages of pregnancy may be of significance.

Yin Yang 1 Promotes Hepatic Gluconeogenesis Through Upregulation of Glucocorticoid Receptor

PubMed Central

Lu, Yan; Xiong, Xuelian; Wang, Xiaolin; Zhang, Zhijian; Li, Jin; Shi, Guojun; Yang, Jian; Zhang, Huijie; Ning, Guang; Li, Xiaoying

2013-01-01

Gluconeogenesis is critical in maintaining blood glucose levels in a normal range during fasting. In this study, we investigated the role of Yin Yang 1 (YY1), a key transcription factor involved in cell proliferation and differentiation, in the regulation of hepatic gluconeogenesis. Our data showed that hepatic YY1 expression levels were induced in mice during fasting conditions and in a state of insulin resistance. Overexpression of YY1 in livers augmented gluconeogenesis, raising fasting blood glucose levels in C57BL/6 mice, whereas liver-specific ablation of YY1 using adenoviral shRNA ameliorated hyperglycemia in wild-type and diabetic db/db mice. At the molecular level, we further demonstrated that the major mechanism of YY1 in the regulation of hepatic glucose production is to modulate the expression of glucocorticoid receptor. Therefore, our study uncovered for the first time that YY1 participates in the regulation of hepatic gluconeogenesis, which implies that YY1 might serve as a potential therapeutic target for hyperglycemia in diabetes. PMID:23193188

Expression of angiotensin II receptors in the caprine ovary and improvement of follicular viability in vitro.

PubMed

Bruno, J B; Lima-Verde, I B; Celestino, J J H; Lima, L F; Matos, M H T; Faustino, L R; Donato, M A M; Peixoto, C A; Campello, C C; Silva, J R V; Figueiredo, J R

2016-08-01

This study aimed to evaluate mRNA levels of angiotensin II (ANG II) receptors (AGTR1 and AGTR2) in caprine follicles and to investigate the influence of ANG II on the viability and in vitro growth of preantral follicles. Real-time polymerase chain reaction (PCR) was used to quantify AGTR1 and AGTR2 mRNA levels in the different follicular stages. For culture, caprine ovaries were collected, cut into 13 fragments and then either directly fixed for histological and ultrastructural analysis (fresh control) or placed in culture for 1 or 7 days in α-minumum essential medium plus (α-MEM+) with 0, 1, 5, 10, 50 or 100 ng/ml ANG II. Then, the fragments were destined to morphological, viability and ultrastructural analysis. The results showed that primordial follicles had higher levels of AGTR1 and AGTR2 mRNA than secondary follicles. Granulosa/theca cells from antral follicles had higher levels of AGTR1 mRNA than their respective cumulus-oocyte complex (COCs). After 7 days of culture, ANG II (10 or 50 ng/ml) maintained the percentages of normal follicles compared with α-MEM+. Fluorescence and ultrastructural microscopy confirmed follicular integrity in ANG II (10 ng/ml). In conclusion, a high expression of AGTR1 and AGTR2 is observed in primordial follicles. Granulosa/theca cells from antral follicles had higher levels of AGTR1 mRNA. Finally, 10 ng/ml ANG II maintained the viability of caprine preantral follicles after in vitro culture.

49 CFR 350.301 - What level of effort must a State maintain to qualify for MCSAP funding?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false What level of effort must a State maintain to... What level of effort must a State maintain to qualify for MCSAP funding? (a) The State must maintain... funds and State matching funds, for CMV safety programs eligible for funding under this part at a level...

49 CFR 350.301 - What level of effort must a State maintain to qualify for MCSAP funding?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false What level of effort must a State maintain to... What level of effort must a State maintain to qualify for MCSAP funding? (a) The State must maintain... funds and State matching funds, for CMV safety programs eligible for funding under this part at a level...

Vitamin A Metabolism: An Update

PubMed Central

D’Ambrosio, Diana N.; Clugston, Robin D.; Blaner, William S.

2011-01-01

Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years. PMID:21350678

Residual neurological function after sacral root resection during en-bloc sacrectomy: a systematic review.

PubMed

Zoccali, Carmine; Skoch, Jesse; Patel, Apar S; Walter, Christina M; Maykowski, Philip; Baaj, Ali A

2016-12-01

Sacrectomy is a highly demanding surgery representing the main treatment for primary tumors arising in the sacrum and pelvis. Unfortunately, it is correlated with loss of important function depending on the resection level and nerve roots sacrificed. The current literature regarding residual function after sacral resection comes from several small case series. The goal of this review is to appraise residual motor function and gait, sensitivity, bladder, bowel, and sexual function after sacrectomies, with consideration to the specific roots sacrificed. An exhaustive literature search was conducted. All manuscripts published before May 2015 regarding residual function after sacrectomy were considered; if a clear correlation between root level and functioning was not present, the paper was excluded. The review identified 15 retrospective case series, totaling 244 patients; 42 patients underwent sacrectomies sparing L4/L4, L4/L5 and L5/L5; 45 sparing both L5 and one or both S1 roots; 8 sparing both S1 and one S2; 48 sparing both S2; 11 sparing both S2 and one S3, 54 sparing both S3, 9 sparing both S3 and one or both S4, and 27 underwent unilateral variable resection. Patients who underwent a sacrectomy maintained functionally normal ambulation in 56.2 % of cases when both S2 roots were spared, 94.1 % when both S3 were spared, and in 100 % of more distal resections. Normal bladder and bowel function were not present when both S2 were cut. When one S2 root was spared, normal bladder function was present in 25 % of cases; when both S2 were spared, 39.9 %; when one S3 was spared, 72.7 %; and when both S3 were spared, 83.3 %. Abnormal bowel function was present in 12.5 % of cases when both S1 and one S2 were spared; in 50.0 % of cases when both S2 were spared; and in 70 % of cases when one S3 was spared; if both S3 were spared, bowel function was normal in 94 % of cases. When even one S4 root was spared, normal bladder and bowel function were present in 100 % of cases. Unilateral sacral nerve root resection preserved normal bladder function in 75 % of cases and normal bowel function in 82.6 % of cases. Motor function depended on S1 root involvement. Total sacrectomy is associated with compromising important motor, bladder, bowel, sensitivity, and sexual function. Residual motor function is dependent on sparing L5 and S1 nerve roots. Bladder and bowel function is consistently compromised in higher sacrectomies; nevertheless, the probability of maintaining sufficient function increases progressively with the roots spared, especially when S3 nerve roots are spared. Unilateral resection is usually associated with more normal function. To the best of our knowledge, this is the first comprehensive literature review to analyze published reports of residual sacral nerve root function after sacrectomy.

Thymus and activation-regulated chemokine as a clinical biomarker in atopic dermatitis.

PubMed

Kataoka, Yoko

2014-03-01

Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the T-helper 2 chemokine family. In Japan, serum TARC level has been commercially measured since 2008. After years of experience, we realized that TARC is an extremely useful clinical biomarker for atopic dermatitis (AD) treatment. Usually, physicians conduct a visual examination to determine whether their treatment has been successful; however, the visual examination results may not always be accurate; in such cases, serum TARC levels should be measured to eliminate any ambiguity regarding the treatment outcome. When the waning and waxing of eczema and fluctuations in the serum TARC levels were considered, we frequently found that AD does not follow a natural course but follows non-regulated inflammatory floating caused by insufficient intermittent topical treatment. Serum TARC is a promising biomarker for remission and can be used for accurately monitoring proactive treatment for long-term control. Abnormally high serum TARC levels indicate accelerated pathogenesis of cutaneous inflammation. Rapid normalization and maintaining normal serum TARC levels using appropriate topical treatment is a reasonable strategy for alleviating inflammation without upregulating cytokine expression. Observing serum TARC levels during early intervention for severe infantile AD is worthwhile to determine initial disease activity and evaluate treatment efficacy. Appropriate control of severe early-onset infantile AD is important for improving prognosis of eczema and for preventing food allergies. Additionally, this biomarker is useful for improving patient adherence. Dermatologists will be able to make great progress in treating AD by adopting biomarkers such as TARC for accurately assessing non-visible subclinical disorders. © 2014 Japanese Dermatological Association.

Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study.

PubMed

Yu, Siming; Cai, Jingxia

2003-03-27

The effects of aniracetam on extracellular amino acid levels in the hippocampus of conscious gerbils, with or without transient cerebral ischemia/reperfusion, were measured by microdialysis and reverse phase-high performance liquid chromatography. Increased extracellular levels of aspartate and glutamate that were observed in the hippocampus of conscious gerbils during transient global forebrain ischemia were reversed by aniracetam. In contrast, the level of extracellular gamma-aminobutyric acid was increased, while taurine was maintained at a higher level than other amino acids by administration of aniracetam (100 mg/kg, p.o.) 60 min before ischemia. Further, in contrast to ischemic animals, administration of aniracetam (100 mg/kg, p.o.) enhanced the release of glutamate and aspartate in the normal gerbil hippocampus. The results suggest that these effects might be due to a partial calcium agonist activity of aniracetam, and that the effects of aniracetam on amino acid levels might be a mechanism of protection against delayed neuronal death in the ischemic hippocampus, thereby improving memory dysfunction induced by ischemia/reperfusion.

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

NASA Technical Reports Server (NTRS)

Fiorindo, R. P.; Negulesco, J. A.

1980-01-01

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Cognitive function in elderly marathon runners: cross-sectional data from the marathon trial (APSOEM).

PubMed

Winker, Robert; Lukas, Ina; Perkmann, Thomas; Haslacher, Helmut; Ponocny, Elisabeth; Lehrner, Johann; Tscholakoff, Dimiter; Dal-Bianco, Peter

2010-12-01

Cognitive impairment of the elderly contributes to morbidity, loss of quality of life, and impairment of work ability in aging western societies. Thus strategies to maintain cognitive function at an advanced age imply a great challenge to Occupational Medicine. To study whether intensive endurance exercise training is associated with better cognitive performance and increases brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF). Active elderly marathon runners or bicyclists older than 60 years were recruited and matched with an inactive control group according to age, sex, and education years. After exclusion of various diseases according to the study protocol 56 athletes and 58 controls could be selected for follow-up studies. The influence of endurance training on cognitive function was assessed by the use of the Vienna Neuropsychological Test Battery and the CERAD test battery. Other relevant outcomes were the levels of BDNF, IGF-1, Apo e4 carrier state, and self-ratings. The elderly marathon group performed better only in one specific cognitive task (the Five Point Test, p = 0.04) and almost significantly better in one additional test (the NAI Stroop Test, p = 0.08). Neither BDNF nor IGF-1 was related to the duration of daily exercise and no differences in the basal levels of these humoral growth factors in the exercise and the control cohort were found. Interestingly, we also found significantly decreased BDNF levels in subjects with Alzheimer's disease in the family in spite of the maintained normal cognitive performance (p = 0.01). These results suggest that extensive endurance exercise training might be beneficial for maintaining cognitive function in elderly persons. Our data demonstrate that beneficial endurance training effects are not linked to the upregulation of the examined neurotrophins. Since we found reduced BDNF-levels in subjects with a positive family history of Alzheimer's disease, we speculate that BDNF-reduction might precede cognitive impairment.

Static Postural Stability Is Normal in Dyslexic Children.

ERIC Educational Resources Information Center

Brown, Brian; And Others

1985-01-01

An experiment on 15 dyslexic and 23 carefully matched control subjects (10- to 12-year-old males), examining their ability to maintain standing posture with eyes open and closed and with standard and tandem foot placement, revealed no differences under any condition tested and no differences in use of visual information to maintain their posture.…

26 CFR 1.401(a)-11 - Qualified joint and survivor annuities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... attained) while in active service of the employer maintaining the plan, or (C) In the case of a plan which... normal retirement age is attained while employed by an employer maintaining the plan. (2) Certain cash... consisting of X Corporation stock, (3) five equal annual cash payments, (4) a life annuity, or (5) a...

26 CFR 1.401(a)-11 - Qualified joint and survivor annuities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... attained) while in active service of the employer maintaining the plan, or (C) In the case of a plan which... normal retirement age is attained while employed by an employer maintaining the plan. (2) Certain cash... consisting of X Corporation stock, (3) five equal annual cash payments, (4) a life annuity, or (5) a...

A simple and effective radiometric correction method to improve landscape change detection across sensors and across time

USGS Publications Warehouse

Chen, X.; Vierling, Lee; Deering, D.

2005-01-01

Satellite data offer unrivaled utility in monitoring and quantifying large scale land cover change over time. Radiometric consistency among collocated multi-temporal imagery is difficult to maintain, however, due to variations in sensor characteristics, atmospheric conditions, solar angle, and sensor view angle that can obscure surface change detection. To detect accurate landscape change using multi-temporal images, we developed a variation of the pseudoinvariant feature (PIF) normalization scheme: the temporally invariant cluster (TIC) method. Image data were acquired on June 9, 1990 (Landsat 4), June 20, 2000 (Landsat 7), and August 26, 2001 (Landsat 7) to analyze boreal forests near the Siberian city of Krasnoyarsk using the normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), and reduced simple ratio (RSR). The temporally invariant cluster (TIC) centers were identified via a point density map of collocated pixel VIs from the base image and the target image, and a normalization regression line was created to intersect all TIC centers. Target image VI values were then recalculated using the regression function so that these two images could be compared using the resulting common radiometric scale. We found that EVI was very indicative of vegetation structure because of its sensitivity to shadowing effects and could thus be used to separate conifer forests from deciduous forests and grass/crop lands. Conversely, because NDVI reduced the radiometric influence of shadow, it did not allow for distinctions among these vegetation types. After normalization, correlations of NDVI and EVI with forest leaf area index (LAI) field measurements combined for 2000 and 2001 were significantly improved; the r 2 values in these regressions rose from 0.49 to 0.69 and from 0.46 to 0.61, respectively. An EVI "cancellation effect" where EVI was positively related to understory greenness but negatively related to forest canopy coverage was evident across a post fire chronosequence with normalized data. These findings indicate that the TIC method provides a simple, effective and repeatable method to create radiometrically comparable data sets for remote detection of landscape change. Compared to some previous relative radiometric normalization methods, this new method does not require high level programming and statistical skills, yet remains sensitive to landscape changes occurring over seasonal and inter-annual time scales. In addition, the TIC method maintains sensitivity to subtle changes in vegetation phenology and enables normalization even when invariant features are rare. While this normalization method allowed detection of a range of land use, land cover, and phenological/biophysical changes in the Siberian boreal forest region studied here, it is necessary to further examine images representing a wide variety of ecoregions to thoroughly evaluate the TIC method against other normalization schemes. ?? 2005 Elsevier Inc. All rights reserved.

Is there an association between body temperature and serum lactate levels in hip fracture patients?

PubMed

Murtuza, F; Farrier, A J; Venkatesan, M; Smith, R; Khan, A; Uzoigwe, C E; Chami, G

2015-10-01

Introduction Hyperlactataemia is associated with adverse outcomes in trauma cases. It is thought to be the result of anaerobic respiration during hypoperfusion. This produces much less energy than complete aerobic glycolysis. Low body temperature in the injured patient carries an equally poor prognosis. Significant amounts of energy are expended in maintaining euthermia. Consequently, there may be a link between lactate levels and dysthermia. Hyperlactataemia may be indicative of inefficient energy production and therefore insufficient energy to maintain euthermia. Alternatively, significant amounts of available oxygen may be sequestered in thermoregulation, resulting in anaerobic respiration and lactate production. Our study investigated whether there is an association between lactate levels and admission body temperature in hip fracture patients. Furthermore, it looked at whether there is a difference in the mean lactate levels between hip fracture patients with low (<36.5°C), normal (36.5-37.5°C) and high (>37.5°C) body temperature on admission, and for patients who have low body temperature, whether there is a progressive rise in serum lactate levels as body temperature falls. Methods The admission temperature and serum lactate of 1,162 patients presenting with hip fracture were recorded. Patients were divided into the euthermic (body temperature 36.5-37.5°C), the pyrexial (>37.5°C) and those with low body temperature (<36.5°C). Admission lactate and body temperature were compared. Results There was a significant difference in age between the three body temperature groups (p=0.007). The pyrexial cohort was younger than the low body temperature group (mean: 78 vs 82 years). Those with low body temperature had a higher mean lactate level than the euthermic (2.2mmol/l vs 2.0mmol/l, p=0.03). However, there was no progressive rise in serum lactate level as admission temperature fell. Conclusions The findings suggest that in hip fracture patients, the body attempts initially to maintain euthermia, incurring an oxygen debt. This would explain the difference in lactate level between the low body temperature and euthermic cohorts. The fact that there is no correlation with the degree of temperature depression and lactate levels indicates that the body does not fuel thermohomeostasis indefinitely with oxygen. Instead, in part, it abandons thermoregulatory mechanisms. Consequently, in this population, active rewarming may be indicated rather than depending on patients' own thermogenic ability.

Polyamine catabolism is enhanced after traumatic brain injury.

PubMed

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A; Strauss, Kenneth I

2010-03-01

Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N(1)-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6-24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6-24 h), then increased by approximately 50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6-72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24-72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies.

Updated US and Canadian Normalization Factors for TRACI 2.1

EPA Science Inventory

The objectives of this study is to update the normalization factors (NFs) of U.S.EPA’s TRACI 2.1 LCIA method (Bare, 2012) for the United States (US) and US-Canadian (US-CA) regions. This is done for the reference year 2008. This was deemed necessary to maintain the representative...

26 CFR 1.503(a)-1 - Denial of exemption to certain organizations engaged in prohibited transactions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... educational organization which normally maintains a regular faculty and curriculum and normally has a... application of section 503(b) may be illustrated by the following examples: Example 1. A creates a foundation in 1954 ostensibly for educational purposes. B, a trustee, accumulates the foundation's income from...

Introduction to "Queering the Writing Center"

ERIC Educational Resources Information Center

Eodice, Michele

2010-01-01

Queer theory challenges what is "normal" and questions the mechanics behind individuals and their institutions' efforts to maintain "normal." Queer theory can help a person get over himself/herself, and, as a result, the words, bodies, spaces, and beliefs that he/she holds dear will be called upon to respond. Harry Denny's article instructs…

Non-Essential Role for TLR2 and Its Signaling Adaptor Mal/TIRAP in Preserving Normal Lung Architecture in Mice

PubMed Central

Ruwanpura, Saleela M.; McLeod, Louise; Lilja, Andrew R.; Brooks, Gavin; Dousha, Lovisa F.; Seow, Huei J.; Bozinovski, Steven; Vlahos, Ross; Hertzog, Paul J.; Anderson, Gary P.; Jenkins, Brendan J.

2013-01-01

Myeloid differentiation factor 88 (MyD88) and MyD88-adaptor like (Mal)/Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) play a critical role in transducing signals downstream of the Toll-like receptor (TLR) family. While genetic ablation of the TLR4/MyD88 signaling axis in mice leads to pulmonary cell death and oxidative stress culminating in emphysema, the involvement of Mal, as well as TLR2 which like TLR4 also signals via MyD88 and Mal, in the pathogenesis of emphysema has not been studied. By employing an in vivo genetic approach, we reveal here that unlike the spontaneous pulmonary emphysema which developed in Tlr4−/− mice by 6 months of age, the lungs of Tlr2−/− mice showed no physiological or morphological signs of emphysema. A more detailed comparative analysis of the lungs from these mice confirmed that elevated oxidative protein carbonylation levels and increased numbers of alveolar cell apoptosis were only detected in Tlr4−/− mice, along with up-regulation of NADPH oxidase 3 (Nox3) mRNA expression. With respect to Mal, the architecture of the lungs of Mal−/− mice was normal. However, despite normal oxidative protein carbonylation levels in the lungs of emphysema-free Mal−/− mice, these mice displayed increased levels of apoptosis comparable to those observed in emphysematous Tlr4−/− mice. In conclusion, our data provide in vivo evidence for the non-essential role for TLR2, unlike the related TLR4, in maintaining the normal architecture of the lung. In addition, we reveal that Mal differentially facilitates the anti-apoptotic, but not oxidant suppressive, activities of TLR4 in the lung, both of which appear to be essential for TLR4 to prevent the onset of emphysema. PMID:24205107

Modeling thrombin generation: plasma composition based approach.

PubMed

Brummel-Ziedins, Kathleen E; Everse, Stephen J; Mann, Kenneth G; Orfeo, Thomas

2014-01-01

Thrombin has multiple functions in blood coagulation and its regulation is central to maintaining the balance between hemorrhage and thrombosis. Empirical and computational methods that capture thrombin generation can provide advancements to current clinical screening of the hemostatic balance at the level of the individual. In any individual, procoagulant and anticoagulant factor levels together act to generate a unique coagulation phenotype (net balance) that is reflective of the sum of its developmental, environmental, genetic, nutritional and pharmacological influences. Defining such thrombin phenotypes may provide a means to track disease progression pre-crisis. In this review we briefly describe thrombin function, methods for assessing thrombin dynamics as a phenotypic marker, computationally derived thrombin phenotypes versus determined clinical phenotypes, the boundaries of normal range thrombin generation using plasma composition based approaches and the feasibility of these approaches for predicting risk.

Three-component homeostasis control

NASA Astrophysics Data System (ADS)

Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

2014-03-01

Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use.

PubMed

Gilman, J; Shanahan, F; Cashman, K D

2006-07-01

To investigate determinants (pathophysiologic and physiologic, behavioural and lifestyle) of vitamin D status in Irish Crohn's disease (CD) patients. A cross-sectional observational study. Cork City, Ireland (52 degrees N). Crohn's Disease patients (n=58; mean age 38.1 years) were recruited from Cork University Hospital. Fifty and nineteen percent of Irish CD patients were vitamin D deficient (defined by serum 25 hydroxyvitamin (OH) D levels <50 nmol/l) during winter and summer, respectively. Multiple regression analysis showed that summer-time serum 25 (OH) D levels were positively associated with use of vitamin D supplements (P=0.033) and negatively associated with smoking (P=0.006) and being male (P=0.063). During winter-time, use of vitamin D supplements (P=0.041) and sun habits (P=0.066) were positively associated, whereas small intestinal involvement (P=0.005) and body mass index (BMI) (P=0.083) were negatively associated with serum 25 (OH) D levels. There was no significant association between other non-pathophysiologic (age, dietary calcium or vitamin D) or pathophysiologic factors (steroid use, resection), and serum 25 (OH) D levels, at either season. Approximately 41 and 60% of the total variation in summer- and winter-time serum 25 (OH) D, respectively, was explained by this model. A high proportion of Irish CD patents had some level of vitamin D deficiency (<50 nmol/l) during late-wintertime. Use of regular low-dose supplemental vitamin D, particularly by patients with small intestinal involvement, cessation of smoking and adequate, but responsible, exposure to summer sunlight as well as maintaining BMI in the normal range could help maintain adequate vitamin D levels during wintertime.

Finding a solution: Heparinised saline versus normal saline in the maintenance of invasive arterial lines in intensive care.

PubMed

Everson, Matthew; Webber, Lucy; Penfold, Chris; Shah, Sanjoy; Freshwater-Turner, Dan

2016-11-01

We assessed the impact of heparinised saline versus 0.9% normal saline on arterial line patency. Maintaining the patency of arterial lines is essential for obtaining accurate physiological measurements, enabling blood sampling and minimising line replacement. Use of heparinised saline is associated with risks such as thrombocytopenia, haemorrhage and mis-selection. Historical studies draw variable conclusions but suggest that normal saline is at least as effective at maintaining line patency, although recent evidence has questioned this. We conducted a prospective analysis of the use of heparinised saline versus normal saline on unselected patients in the intensive care of our hospital. Data concerning duration of 471 lines insertion and reason for removal was collected. We found a higher risk of blockage for lines flushed with normal saline compared with heparinised saline (RR = 2.15, 95% CI 1.392-3.32, p  ≤ 0.001). Of the 56 lines which blocked initially (19 heparinised saline and 37 normal saline lines), 16 were replaced with new lines; 5 heparinised saline lines and 11 normal saline lines were reinserted; 5 of these lines subsequently blocked again, 3 of which were flushed with normal saline. Our study demonstrates a clinically important reduction in arterial line longevity due to blockages when flushed with normal saline compared to heparinised saline. We have determined that these excess blockages have a significant clinical impact with further lines being inserted after blockage, resulting in increased risks to patients, wasted time and cost of resources. Our findings suggest that the current UK guidance favouring normal saline flushes should be reviewed.

Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche.

PubMed

Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

2014-05-13

Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Human testis and testis cancer specimens from orchidectomies were cultured in 'hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.

The use of a tactile interface to convey position and motion perceptions

NASA Technical Reports Server (NTRS)

Rupert, A. H.; Guedry, F. E.; Reschke, M. F.

1994-01-01

Under normal terrestrial conditions, perception of position and motion is determined by central nervous system integration of concordant and redundant information from multiple sensory channels (somatosensory, vestibular, visual), which collectively yield vertical perceptions. In the acceleration environment experienced by the pilots, the somatosensory and vestibular sensors frequently present false information concerning the direction of gravity. When presented with conflicting sensory information, it is normal for pilots to experience episodes of disorientation. We have developed a tactile interface that obtains vertical roll and pitch information from a gyro-stabilized attitude indicator and maps this information in a one-to-one correspondence onto the torso of the body using a matrix of vibrotactors. This enables the pilot to continuously maintain an awareness of aircraft attitude without reference to visual cues, utilizing a sensory channel that normally operates at the subconscious level. Although initially developed to improve pilot spatial awareness, this device has obvious applications to 1) simulation and training, 2) nonvisual tracking of targets, which can reduce the need for pilots to make head movements in the high-G environment of aerial combat, and 3) orientation in environments with minimal somatosensory cues (e.g., underwater) or gravitational cues (e.g., space).

Effects of stripped oil shale retort water on fishes, birds, and mammals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nystrom, R.R.

1983-01-01

Golden hamsters (Mesocricetus auratus Water), coturnix quail (Coturnix coturnix Teminck and Schlegal), fathead minnows (Pimphales promelas Rafinesque), and rainbow trout (Salmo gairdneri Richardson) were subjected to various exposures of stripped oil shale retort water (SRW). Chronic low-level exposures of all experimental animals to SRW revealed no adverse histological effects attributable to SRW. Also, production and development of second generation fathead minnows and coturnix quail exposed to SRW was normal. Subacute exposure of rainbow trout to SRW produced ultrastructural changes detected by transmission, scanning, and freeze fracture electron microscopy) in the gill, liver, and kidney tissues. The gills showed a swellingmore » of secondary lamellae, disorganization of normal tissue architecture, and sloughing of respiratory cells. The liver contained lamellar bodies not seen in the controls. Relatively large, electron dense, membrane-bounded deposits were present in proximal tubule cells of the kidney. Sodium arsenite (a significant component of SRW) was shown to cause swelling of granular endosplasmic reticulum in quail liver tissue with an acute exposure. This effect could be related to the fact that arsenic inhibits ATP production, which would decrease the ability of the sodium pumps to maintain a normal osmotic balance.« less

Biological Perspectives of Delayed Fracture Healing

PubMed Central

Hankenson, KD; Zmmerman, G; Marcucio, R

2015-01-01

Fracture healing is a complex biological process that requires interaction among a series of different cell types. Maintaining the appropriate temporal progression and spatial pattern is essential to achieve robust healing. We can temporally assess the biological phases via gene expression, protein analysis, histologically, or non-invasively using biomarkers as well as imaging techniques. However, determining what leads to normal verses abnormal healing is more challenging. Since the ultimate outcome of the process of fracture healing is to restore the original functions of bone, assessment of fracture healing should include not only monitoring the restoration of structure and mechanical function, but also an evaluation of the restoration of normal bone biology. Currently very few non-invasive measures of the biology of healing exist; however, recent studies that have correlated non-invasive measures with fracture healing outcome in humans have shown that serum TGFbeta1 levels appear to be an indicator of healing vs non-healing. In the future, developing additional serum measures to assess biological healing will improve the reliability and permit us to assess stages of fracture healing. Additionally, new functional imaging technologies could prove useful for better understanding both normal fracture healing and predicting dysfunctional healing in human patients. PMID:24857030

The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans*♦

PubMed Central

Chun, Haarin; Sharma, Anuj Kumar; Lee, Jaekwon; Chan, Jefferson; Jia, Shang; Kim, Byung-Eun

2017-01-01

Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans. Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways. PMID:27881675

Opportunities for Joint Water–Energy Management: Sensitivity of the 2010 Western U.S. Electricity Grid Operations to Climate Oscillations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voisin, N.; Kintner-Meyer, M.; Wu, D.

The 2016 SECURE Water Act report’s natural water availability benchmark, combined with the 2010 level of water demand from an integrated assessment model, is used as input to drive a large-scale water management model. The regulated flow at hydropower plants and thermoelectric plants in the Western U.S. electricity grid (WECC) is translated into potential hydropower generation and generation capacity constraints. The impact on reliability (unserved energy, reserve margin) and cost (production cost, carbon emissions) of water constraints on 2010-level WECC power system operations is assessed using an electricity production cost model (PCM). Use of the PCM reveals the changes inmore » generation dispatch that reflect the inter-regional interdependencies in water-constrained generation and the ability to use other generation resources to meet all electricity loads in the WECC. August grid operational benchmarks show a range of sensitivity in production cost (-8 to +11%) and carbon emissions (-7 to 11%). The reference reserve margin threshold of 15% above peak load is maintained in the scenarios analyzed, but in 5 out of 55 years unserved energy is observed when normal operations are maintained. There is 1 chance in 10 that a year will demonstrate unserved energy in August, which defines the system’s historical performance threshold to support impact, vulnerability, and adaptation analysis. For seasonal and longer term planning, i.e., multi-year drought, we demonstrate how the Water Scarcity Grid Impact Factor and climate oscillations (ENSO, PDO) can be used to plan for joint water-electricity management to maintain grid reliability.« less

Human colonic crypts in culture: segregation of immunochemical markers in normal versus adenoma-derived.

PubMed

Dame, Michael K; Jiang, Yan; Appelman, Henry D; Copley, Kelly D; McClintock, Shannon D; Aslam, Muhammad Nadeem; Attili, Durga; Elmunzer, B Joseph; Brenner, Dean E; Varani, James; Turgeon, D Kim

2014-02-01

In order to advance a culture model of human colonic neoplasia, we developed methods for the isolation and in vitro maintenance of intact colonic crypts from normal human colon tissue and adenomas. Crypts were maintained in three-dimensional Matrigel culture with a simple, serum-free, low Ca(2+) (0.15 mM) medium. Intact colonic crypts from normal human mucosa were viably maintained for 3-5 days with preservation of the in situ crypt-like architecture, presenting a distinct base and apex. Abnormal structures from adenoma tissue could be maintained through multiple passages (up to months), with expanding buds/tubules. Immunohistochemical markers for intestinal stem cells (Lgr5), growth (Ki67), differentiation (E-cadherin, cytokeratin 20 (CK20) and mucin 2 (MUC2)) and epithelial turnover (Bax, cleaved Caspase-3), paralleled the changes in function. The epithelial cells in normal crypts followed the physiological sequence of progression from proliferation to differentiation to dissolution in a spatially and temporally appropriate manner. Lgr5 expression was seen in a few basal cells of freshly isolated crypts, but was not detected after 1-3 days in culture. After 24 h in culture, crypts from normal colonic tissue continued to show strong Ki67 and MUC2 expression at the crypt base, with a gradual decrease over time such that by days 3-4 Ki67 was not expressed. The differentiation marker CK20 increased over the same period, eventually becoming intense throughout the whole crypt. In adenoma-derived structures, expression of markers for all stages of progression persisted for the entire time in culture. Lgr5 showed expression in a few select cells after months in culture. Ki67 and MUC2 were largely associated with the proliferative budding regions while CK20 was localized to the parent structure. This ex vivo culture model of normal and adenomatous crypts provides a readily accessible tool to help understand the growth and differentiation process in human colonic epithelium.

The cell biology of aging.

PubMed

Hayflick, L

1985-02-01

It is only within the past ten years that biogerontology has become attractive to a sufficient number of biologists so that the field can be regarded as a seriously studied discipline. Cytogerontology, or the study of aging at the cellular level, had its genesis about 20 years ago when the dogma that maintained that cultured normal cells could replicate forever was overturned. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Only abnormal somatic cells are capable of immortality. In recent years it has been found that the number of population doublings of which cultured normal cells are capable is inversely proportional to donor age. There is also good evidence that the number of population doublings of cultured normal fibroblasts is directly proportional to the maximum lifespan of ten species that have been studied. Cultures prepared from patients with accelerated aging syndromes (progeria and Werner's syndrome) undergo far fewer doublings than do those of age-matched controls. The normal human fibroblast cell strain WI-38 was established in 1962 from fetal lung, and several hundred ampules of these cells were frozen in liquid nitrogen at that time. These ampules have been reconstituted periodically and shown to be capable of replication. This represents the longest period of time that a normal human cell has ever been frozen. Normal human fetal cell strains such as WI-38 have the capacity to double only about 50 times. If cultures are frozen at various population doublings, the number of doublings remaining after reconstitution is equal to 50 minus the number of doublings that occurred prior to freezing. The memory of the cells has been found to be accurate after 23 years of preservation in liquid nitrogen. Normal human cells incur many physiologic decrements that herald the approach of their failure to divide. Many of these functional decrements are identical to decrements found in humans as they age. Thus it is likely that these decrements are also the precursors of age changes in vivo. The finite replicative capacity of normal cells is never seen to occur in vivo because aging and death of the individual occurs well before the doubling limit is reached.

Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

PubMed

Shiota, K; Furuyama, N; Takahashi, M

1991-10-01

The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of soybean isoflavone on born metabolism and morphology in animal model of osteoporosis rats].

PubMed

Yu, Qing; Su, Yi-xiang; Wang, Wen-wei; Li, An-le; Liu, Cun-li; Wang, Yi-long; Hu, Wan-li

2007-07-01

To study the effects of soybean isoflavone (SI) on born metabolism and morphology in animal model of osteoporosis rats. All 70 female Sprague-Dawley (SD) rats were randomly divided into 7 groups according to the levels of total cholesterol (TC) in serum: hyper-lipoid group, estrogen group, low-dose SI group, middle-dose SI group, high-dose SI group, sham group and normal control groups. Bilateral ovaries were extirpated except sham and normal control groups. Except the rats in normal control group, the other rats were fed with high fat diet. Body weight was weighted ad unam vice per week. The estrogen, different dose of SI or deionized water were fed with intragastric administration for 12 weeks. Vena caudalis serum were collected after being ovariectomized, administered for 4 w, 8 w and killed. Serum alkaline phosphatase (AKP) activity and bone density were measured etc. To interfere of estrogen and SI might recover AKP enzyme activity after its being ovariectomized. There almost sowed no differences between high dose SI intervention and estrogen on bone density and microstructure. Bone loss due to being ovariectomized was relieved after SI intervention. SI might protect cardiocyte myofilament and mitochondrial ultramicrostructure. There was mirror image in estrogen, high dose SI group resembling the normal control group, and there was obvious damage in hyper-lipoids group. There should be effects of high dose SI on bone metabolism and morphology in animal model of osteoporosis rats. Serum AKP enzyme activity and bone density should have significantly recovered, the serum level of calcium and phosphorus were maintained after high dose intervened but no significant effects for low dose of SI.

Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice.

PubMed

Tsuneki, Hiroshi; Tokai, Emi; Nakamura, Yuya; Takahashi, Keisuke; Fujita, Mikio; Asaoka, Takehiro; Kon, Kanta; Anzawa, Yuuki; Wada, Tsutomu; Takasaki, Ichiro; Kimura, Kumi; Inoue, Hiroshi; Yanagisawa, Masashi; Sakurai, Takeshi; Sasaoka, Toshiyasu

2015-02-01

Circadian rhythm is crucial for preventing hepatic insulin resistance, although the mechanism remains uncovered. Here we report that the wake-active hypothalamic orexin system plays a key role in this regulation. Wild-type mice showed that a daily rhythm in blood glucose levels peaked at the awake period; however, the glucose rhythm disappeared in orexin knockout mice despite normal feeding rhythm. Central administration of orexin A during nighttime awake period acutely elevated blood glucose levels but subsequently lowered daytime glucose levels in normal and diabetic db/db mice. The glucose-elevating and -lowering effects of orexin A were suppressed by adrenergic antagonists and hepatic parasympathectomy, respectively. Moreover, the expression levels of hepatic gluconeogenic genes, including Pepck, were increased and decreased by orexin A at nanomolar and femtomolar doses, respectively. These results indicate that orexin can bidirectionally regulate hepatic gluconeogenesis via control of autonomic balance, leading to generation of the daily blood glucose oscillation. Furthermore, during aging, orexin deficiency enhanced endoplasmic reticulum (ER) stress in the liver and caused impairment of hepatic insulin signaling and abnormal gluconeogenic activity in pyruvate tolerance test. Collectively, the daily glucose rhythm under control of orexin appears to be important for maintaining ER homeostasis, thereby preventing insulin resistance in the liver. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

[Cytogenetical comparison of restorers TP-4 and D minghui63 and maintainer D46B of autotetraploid rice].

PubMed

Long, Wen-Bo; Luan, Li; Wang, Xing; Liu, Yu-Hua; Tu, Sheng-Bin; Kong, Fan-Lun; He, Tao

2007-04-01

Cytogenetical comparison was made between high seed set restorers TP-4 and D minghui63 and eminent maintainer line D46B of autotetraploid rice. The meiosis observation demonstrated the genomes of our autotetraploid materials were all 2n = 48, the same as those in mitosis observation. Low percentages of univalent and trivalent in metaphase I (MI) of restorers TP-4 and D minghui63 and in metaphase I (MI) of maintainer line D46B of autotetraploid rice were observed. And the percentages of chromosome pairing were all over 99%, showing eminent cytological character. The frequency of TP-4 and D minghui63 in metaphase I (MI) was 2.00/PMC and 2.26/PMC, respectively. However the frequency of D46B was 6.00/PMC, significantly higher than those of TP-4 and D minghui63. It indicated that the maintainer D46B has better chromosome pairing capability in metaphase I (MI). While, the frequency of lagging chromosomes of the maintainer D46B in anaphase I (AI) was 10.62%, significantly lower than that of TP-4 (19.44%) or D minghui63 (23.14%), and it was close to the level of diploid control (7.30%). In telophase I (TI), maintainer D46B exhibited a lower frequency of microkernel, and in telophase II (TII) the frequency of normal quartered microspore of maintainer D46B was not only higher than that of TP-4 or D minghui63 but also than that of diploid control. The percentage of the cell observed chromosome lagging in A1 and the percentage of abnormal cell in TI showed a greatly significant positive correlation. That may demonstrate chromo some separation in anaphase I (AI) and microkernel formation in telophase I (TI) are controlled by the same dominant single gene or the major gene of QTL.

Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

PubMed

Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

2010-11-01

During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BG<70 mg/dl). After a global adjustment of control algorithm parameters used to model insulin absorption and clearance to more closely match insulin pharmacokinetic (PK) parameters observed in the study cohort, administration of glucagon by the control system was more effective in preventing hypoglycemia. We evaluated the role of plasma insulin and plasma glucagon levels in determining whether glucagon was effective in preventing hypoglycemia. We identified and analyzed 36 episodes during which glucagon was given and categorized them as either successful or unsuccessful in preventing hypoglycemia. In 20 of the 36 episodes, glucagon administration prevented hypoglycemia. In the remaining 16, BG fell below 70 mg/dl (12 of the 16 occurred during experiments performed before PK parameters were adjusted). The (dimensionless) levels of plasma insulin (normalized relative to each subject's baseline insulin level) were significantly higher during episodes ending in hypoglycemia (5.2 versus 3.7 times the baseline insulin level, p=.01). The relative error in the control algorithm's online estimate of the instantaneous plasma insulin level was also higher during episodes ending in hypoglycemia (50 versus 30%, p=.003), as were the peak plasma glucagon levels (183 versus 116 pg/ml, p=.007, normal range 50-150 pg/ml) and mean plasma glucagon levels (142 versus 75 pg/ml, p=.02). Relative to mean plasma insulin levels, mean plasma glucagon levels tended to be 59% higher during episodes ending in hypoglycemia, although this result was not found to be statistically significant (p=.14). The rate of BG descent was also significantly greater during episodes ending in hypoglycemia (1.5 versus 1.0 mg/dl/min, p=.02). Microdose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

Switching from high-fat to low-fat diet normalizes glucose metabolism and improves glucose-stimulated insulin secretion and insulin sensitivity but not body weight in C57BL/6J mice.

PubMed

Agardh, Carl-David; Ahrén, Bo

2012-03-01

Environmental factors such as a high-fat diet contribute to type 2 diabetes and obesity. This study examined glycemia, insulin sensitivity, and β-cell function after switching from a high-fat diet to a low-fat diet in mice. C57BL/6J mice were fed a high-fat diet or low-fat diet for 18 months, after which mice on the high-fat diet either maintained this diet or switched to a low-fat diet for 4 weeks. Body weight and glucose and insulin responses to intraperitoneal glucose were determined. Insulin secretion (insulinogenic index: the 10-minute insulin response divided by the 10-minute glucose level) and insulin sensitivity (1 divided by basal insulin) were determined. After 18 months on a high-fat diet, mice had glucose intolerance, marked hyperinsulinemia, and increased body weight compared to mice on a low-fat diet (P < 0.001). Switching from a high-fat diet to low-fat diet normalized glucose tolerance, reduced but not normalized body weight (P < 0.001), increased insulin secretion (248 ± 39 vs 141 ± 46 pmol/mmol; P = 0.028) and improved but not normalized insulin sensitivity (3.2 ± 0.1 vs 1.0 ± 0.1 [pmol/L]; P = 0.012). Switching from a high-fat diet to low-fat diet normalizes glucose tolerance and improves but not normalizes insulin secretion and insulin sensitivity. These effects are more pronounced than the reduced body weight.

Metal ion levels in patients with stainless steel spinal instrumentation.

PubMed

McPhee, I Bruce; Swanson, Cheryl E

2007-08-15

Case-control study. To determine whether metal ion concentrations are elevated in patients with spinal instrumentation. Studies have shown that serum and urinary levels of component metal ions are abnormally elevated in patients with total joint arthroplasties. Little is known of metal ion release and concentrations in patients with spinal instrumentation. The study group consisted of patients who had undergone spinal instrumentation for various spinal disorders with a variety of stainless steel implants, 5 to 25 years previously. A group of volunteers without metal implants were controls. All subjects were tested for serum nickel, blood chromium, and random urine chromium/creatinine ratio estimation. The study group consisted of 32 patients with retained implants and 12 patients whose implants had been removed. There were 26 unmatched controls. There was no difference in serum nickel and blood chromium levels between all 3 groups. The mean urinary chromium/creatinine ratio for patients with implants and those with implants removed was significantly greater than controls (P < 0.001). The difference between study subgroups was not significant (P = 0.16). Of several patient and instrumentation variables, only the number of couplings approached significance for correlation with the urine chromium excretion (P = 0.07). Spinal implants do not raise the levels of serum nickel and blood chromium. There is evidence that metal ions are released from spinal implants and excreted in urine. The excretion of chromium in patients with spinal implants was significantly greater than normal controls although lower where the implants have been removed. The findings are consistent with low-grade release of ions from implants with rapid clearance, thus maintaining normal serum levels. Levels of metal ions in the body fluids probably do not reach a level that causes late side-effect; hence, routine removal of the implants cannot be recommended.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

Primary intestinal lymphangiectasia in children: is octreotide an effective and safe option in the treatment?

PubMed

Sari, Sinan; Baris, Zeren; Dalgic, Buket

2010-10-01

Octreotide has been suggested as a medical treatment option in refractory cases of primary intestinal lymphangiectasia (IL). There are few data about the long-term effect and safety of octreotide for IL in the literature. In the present article we analyzed pediatric cases of primary IL with long-term octreotide treatment and discussed its safety profile. Between 1999 and 2008, 13 children were diagnosed in our clinic as having IL. Six patients with primary IL were followed up, receiving octreotide therapy. The clinical data of the patients and duration of therapy, dose, and side effects of octreotide were evaluated. Octreotide, 15 to 20 μg per body weight 2 times daily subcutaneously, was given to all of the patients. Duration of the octreotide treatment changed between 3 and 37 months. Stool frequency decreased in all of the patients after starting octreotide treatment. Serum albumin could be maintained at normal levels in 3 patients. The requirement of albumin infusions decreased in all of the patients. Acute pancreatitis was observed as a side effect of octreotide in 1 patient. Octreotide may help to maintain serum albumin levels, improve clinical findings, and decrease the requirement of albumin infusions in refractory cases of primary IL.

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

PubMed Central

Santich, Brian H.; Kim, Jin Young; Posada, Jacqueline G.; Ho, Jason; Buckner, Clarisa M.; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E.; Manischewitz, Jody; King, Lisa R.; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S.; Malech, Harry L.

2012-01-01

CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells. PMID:23074274

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells.

PubMed

Moir, Susan; De Ravin, Suk See; Santich, Brian H; Kim, Jin Young; Posada, Jacqueline G; Ho, Jason; Buckner, Clarisa M; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E; Manischewitz, Jody; King, Lisa R; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S; Malech, Harry L

2012-12-06

CD27(+) memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27(+) but also IgG(+) B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG(+) B cells, the ratio of CD27(-) to CD27(+) was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27(-)IgG(+) B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27(+) counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27(-)IgG(+) B-cell compartment. Together, these findings show that, despite reduced circulating CD27(+) memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27(-) B cells.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konis, Kyle; Orosz, Michael; Sintov, Nicole

Competition-based “energy saving” interventions are increasingly promoted as an effective strategy for reducing energy consumption in buildings with large occupant controlled electrical loads. However, the factors that drive energy savings in such interventions are not well understood, nor are the impacts of short-term competitions on long-term energy performance. A total of 39 8-occupant suites in a freshman residence hall were instrumented with “smart” electric meters, which recorded circuit-level electricity consumption at 15-minute intervals. During a three-week Fall 2014 competition, suites competed to reduce their overall electricity demand and achieved a 6.4% reduction in whole-building demand overall and a 12% reductionmore » during hours of peak demand (from 12:00 to 19:00), despite peak seasonal temperatures and all-time record electricity demand. Analysis incorporating weather-normalized HVAC demand after the competition showed a significant “rebound” for a large portion of the suites (19), however 12 suites made further reductions, and the remainder maintained demand at the competition level. As a result, we compared energy data with self-reported survey data and identified self-efficacy beliefs, pro-environmental behaviors, and sense of affiliation with other residents of the hall as key factors distinguishing the suites with the greatest and most persistent reductions in demand from suites that maintained or increased demand.« less

Parainflammation, chronic inflammation, and age-related macular degeneration.

PubMed

Chen, Mei; Xu, Heping

2015-11-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

PubMed Central

Anderson, W P; Johnston, C I; Korner, P I

1979-01-01

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

Effects of isolation on interferon production and hematological and immunological parameters

NASA Technical Reports Server (NTRS)

Sonnenfeld, G.; Measel, J.; Loken, M. R.; Degioanni, J.; Follini, S.; Galvagno, A.; Montalbini, M.

1992-01-01

A 27-year-old woman was maintained in an isolated state for 131 days in Carlsbad Caverns, New Mexico. Her diet was vitamin D-depleted. Determinations on the effects of such isolation on levels and activities of peripheral blood cells that are important for hematological homeostasis and immunological function were carried out. Throughout the duration of the study, the percentage of lymphoid cells that expressed CD3, CD4, CD8, CD19, Leu 8, and other markers remained relatively constant although the absolute numbers of these cells varied. Although the percentage of natural killer (NK) cells did not vary, the activity of these cells did change. NK cell activity became elevated as the isolation study progressed. Production of interferon-gamma (IFN-gamma) in response to mitogen stimulation was higher than expected throughout the isolation periods, but returned to the normal range after termination of the isolation. Red and white cell counts dropped significantly upon entering isolation, but soon returned to normal.

The transcriptional programme of the androgen receptor (AR) in prostate cancer.

PubMed

Lamb, Alastair D; Massie, Charlie E; Neal, David E

2014-03-01

The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors. © 2013 The Authors. BJU International © 2013 BJU International.

VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch.

PubMed

Lagerström, Malin C; Rogoz, Katarzyna; Abrahamsen, Bjarke; Persson, Emma; Reinius, Björn; Nordenankar, Karin; Olund, Caroline; Smith, Casey; Mendez, José Alfredo; Chen, Zhou-Feng; Wood, John N; Wallén-Mackenzie, Asa; Kullander, Klas

2010-11-04

The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response. Copyright © 2010 Elsevier Inc. All rights reserved.

Dipeptide species regulate p38MAPK–Smad3 signalling to maintain chronic myelogenous leukaemia stem cells

PubMed Central

Naka, Kazuhito; Jomen, Yoshie; Ishihara, Kaori; Kim, Junil; Ishimoto, Takahiro; Bae, Eun-Jin; Mohney, Robert P.; Stirdivant, Steven M.; Oshima, Hiroko; Oshima, Masanobu; Kim, Dong-Wook; Nakauchi, Hiromitsu; Takihara, Yoshihiro; Kato, Yukio; Ooshima, Akira; Kim, Seong-Jin

2015-01-01

Understanding the specific survival of the rare chronic myelogenous leukaemia (CML) stem cell population could provide a target for therapeutics aimed at eradicating these cells. However, little is known about how survival signalling is regulated in CML stem cells. In this study, we survey global metabolic differences between murine normal haematopoietic stem cells (HSCs) and CML stem cells using metabolomics techniques. Strikingly, we show that CML stem cells accumulate significantly higher levels of certain dipeptide species than normal HSCs. Once internalized, these dipeptide species activate amino-acid signalling via a pathway involving p38MAPK and the stemness transcription factor Smad3, which promotes CML stem cell maintenance. Importantly, pharmacological inhibition of dipeptide uptake inhibits CML stem cell activity in vivo. Our results demonstrate that dipeptide species support CML stem cell maintenance by activating p38MAPK–Smad3 signalling in vivo, and thus point towards a potential therapeutic target for CML treatment. PMID:26289811

Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.

PubMed

de Medina, Philippe; Paillasse, Michael R; Segala, Gregory; Voisin, Maud; Mhamdi, Loubna; Dalenc, Florence; Lacroix-Triki, Magali; Filleron, Thomas; Pont, Frederic; Saati, Talal Al; Morisseau, Christophe; Hammock, Bruce D; Silvente-Poirot, Sandrine; Poirot, Marc

2013-01-01

We previously synthesized dendrogenin A and hypothesized that it could be a natural metabolite occurring in mammals. Here we explore this hypothesis and report the discovery of dendrogenin A in mammalian tissues and normal cells as an enzymatic product of the conjugation of 5,6α-epoxy-cholesterol and histamine. Dendrogenin A was not detected in cancer cell lines and was fivefold lower in human breast tumours compared with normal tissues, suggesting a deregulation of dendrogenin A metabolism during carcinogenesis. We established that dendrogenin A is a selective inhibitor of cholesterol epoxide hydrolase and it triggered tumour re-differentiation and growth control in mice and improved animal survival. The properties of dendrogenin A and its decreased level in tumours suggest a physiological function in maintaining cell integrity and differentiation. The discovery of dendrogenin A reveals a new metabolic pathway at the crossroads of cholesterol and histamine metabolism and the existence of steroidal alkaloids in mammals.

PtrA/NINV, an alkaline/neutral invertase gene of Poncirus trifoliata, confers enhanced tolerance to multiple abiotic stresses by modulating ROS levels and maintaining photosynthetic efficiency.

PubMed

Dahro, Bachar; Wang, Fei; Peng, Ting; Liu, Ji-Hong

2016-03-29

Alkaline/neutral invertase (A/N-INV), an enzyme that hydrolyzes sucrose irreversibly into glucose and fructose, is essential for normal plant growth,development, and stress tolerance. However, the physiological and/or molecular mechanism underpinning the role of A/N-INV in abiotic stress tolerance is poorly understood. In this report, an A/N-INV gene (PtrA/NINV) was isolated from Poncirus trifoliata, a cold-hardy relative of citrus, and functionally characterized. PtrA/NINV expression levels were induced by cold, salt, dehydration, sucrose, and ABA, but decreased by glucose. PtrA/NINV was found to localize in both chloroplasts and mitochondria. Overexpression of PtrA/NINV conferred enhanced tolerance to multiple stresses, including cold, high salinity, and drought, as supported by lower levels of reactive oxygen species (ROS), reduced oxidative damages, decreased water loss rate, and increased photosynthesis efficiency, relative to wild-type (WT). The transgenic plants exhibited higher A/N-INV activity and greater reducing sugar content under normal and stress conditions. PtrA/NINV is an important gene implicated in sucrose decomposition, and plays a positive role in abiotic stress tolerance by promoting osmotic adjustment, ROS detoxification and photosynthesis efficiency. Thus, PtrA/NINV has great potential to be used in transgenic breeding for improvement of stress tolerance.

The effect of different methods of leucoreduction on plasma coagulation factors.

PubMed

Aboul Enein, Azza A; Abdel Rahman, Hala A; Abdel Maged, Mohamed M M; El Sissy, Maha H

2017-03-01

Removal of leucocytes from blood products, namely leucoreduction, improves the safety of blood transfusion by reducing adverse events associated with the incidental transfusion of leucocytes. Coagulation factors might be compromised during leucoreduction because of exposure of plasma to a variety of filter materials. The aim of the current study was to assess the effect of different methods of prestorage leucofiltration (apheresis and whole blood filters) on prothrombin time, international normalized ratio, partial thromboplastin time and factors V and VIII. There was a significant prolongation of prothrombin time as well as elevation of international normalized ratio in plasma after leucoreduction (14.5 ± 0.7 s vs. 13.9 ± 0.7 s, P = 0.008 and 1.14 ± 0.07 vs. 1.09 ± 0.07, P = 0.005, respectively). Also, there was a statistically significant prolongation of activated partial thromboplastin time in nonleucoreduced plasma (55.6 ± 9.9 s vs. 43.2 ± 12.8 s, P = 0.001). There was no significant filtration effect on factors V and VIII levels. Furthermore, there was no significant difference in factors V and VIII levels between plasma filtered by inline whole blood filters and apheresis machine. Leucodepleted plasma originating from both inline whole blood filter and apheresis machine maintained satisfactory levels of factors V and VIII.

Difference of the Climatological Monthly Frequency of the Explosive Cyclones in the Northwestern Part of the Pacific and the Atlantic

NASA Astrophysics Data System (ADS)

Tsukijihara, T.; Tomita, T.; Iwao, K.

2015-12-01

　This study examined the climatological monthly frequency of the explosive cyclones over the northwestern(NW) part of the Pacific and the Atlantic in boreal cold season (October-April) from 1979/80 to 2012/13, using the long-term objective analysis data. The climatological monthly frequency of the NW Atlantic is on a normal distribution with a maximum in January, while it deviates from a normal distribution in the NW Pacific, in particular, the deviation is large in March.　Low-level meridional temperature gradient decreases linearly from February to April in the Gulf stream region. However, the gradient is maintained through February to March to the east of Japan, and it sharply weakens in April. This feature is in good agreement with the climatological monthly frequency of the explosive cyclones in the two regions.　The difference in the seasonal change of the low-level meridional temperature gradient in the two regions is caused by the positional relation of the gradient and continents. In particular, the difference of warmed area in the eastern part of the Eurasian and the North American continents causes the difference of the low-level meridional temperature gradient, and it causes the difference in the climatological monthly frequency of the explosive cyclones between the two regions from February to April.

Nature of the Renal Concentrating Defect in Sickle Cell Disease*

PubMed Central

Hatch, Fred E.; Culbertson, James W.; Diggs, Lemuel W.

1967-01-01

Free water reabsorption (TcH2O) measured during 10% mannitol diuresis and subsequently during 3% saline diuresis was compared in patients with sickle cell anemia and in normal subjects. During mannitol infusion, TcH2O progressively rose with increasing osmolar clearance (Cosm) and reached a maximal level in both groups studied. During hypertonic saline diuresis, TcH2O progressively rose in the normal subjects and exceeded the maximal levels attained during mannitol diuresis, with no evidence of a maximal TcH2O level appearing. In contrast, none of the saline curves significantly exceeded the mannitol curves in the sickle cell patients but tended to parallel the mannitol curves at comparable rates of solute clearance. Since TcH2O is an index of both solute (sodium) transport from the loop of Henle and solute accumulation in the hypertonic medullary interstitium, tubular sodium handling was examined in both sickle cell patients and control subjects alike. No difference in the tubular transport of sodium could be demonstrated either under conditions of sodium loading or under conditions in which the tubular sodium load was low (water diuresis). These data support the conclusion that the defect in urinary concentration in sickle cell patients is caused by a limitation in maintaining a high concentration of solute in the medullary interstitium, thus limiting the rate of TcH2O from the collecting duct. PMID:6023770

Effects of combined physical education and nutritional programs on schoolchildren's healthy habits.

PubMed

Gallotta, Maria Chiara; Iazzoni, Sara; Emerenziani, Gian Pietro; Meucci, Marco; Migliaccio, Silvia; Guidetti, Laura; Baldari, Carlo

2016-01-01

Background. A multidisciplinary approach seems to be effective in creating healthy habits in children. The aim of this study was to evaluate the efficacy of three 5-month combined physical education (PE) and nutritional interventions on body composition, physical activity (PA) level, sedentary time and eating habits of schoolchildren. Methods. Anthropometric data, weekly PA level, sedentary time and eating habits of 230 healthy students were analysed using a repeated-measures ANOVA with Group (experimental group 1 vs experimental group 2 vs control group), Adiposity Status (under fat vs normal fat vs obese), and Time (pre vs post) as factors. Results. Body fat mass percentage increased after intervention (18.92 ± 8.61% vs 19.40 ± 8.51%) in all groups. The weekly PA level significantly increased after intervention in both experimental groups. Sedentary time significantly decreased after the intervention period (565.70 ± 252.93 vs 492.10 ± 230.97 min/week, p < 0.0001). Moreover, obese children were more sedentary than under fat and normal fat children. Children significantly changed the consumption of some specific foods after intervention. Discussion. This study revealed the effectiveness of a combined PE and nutritional intervention to improve children's healthful dietary practices and to encourage an active lifestyle. However, it needs a further appropriate development to establish patterns of healthful dietary practices that encourage an active lifestyle with which to maintain healthy habits through life.

Cell Identity Switching Regulated by Retinoic Acid Signaling Maintains Homogeneous Segments in the Hindbrain.

PubMed

Addison, Megan; Xu, Qiling; Cayuso, Jordi; Wilkinson, David G

2018-06-04

The patterning of tissues to form subdivisions with distinct and homogeneous regional identity is potentially disrupted by cell intermingling. Transplantation studies suggest that homogeneous segmental identity in the hindbrain is maintained by identity switching of cells that intermingle into another segment. We show that switching occurs during normal development and is mediated by feedback between segment identity and the retinoic acid degrading enzymes, cyp26b1 and cyp26c1. egr2, which specifies the segmental identity of rhombomeres r3 and r5, underlies the lower expression level of cyp26b1 and cyp26c1 in r3 and r5 compared with r2, r4, and r6. Consequently, r3 or r5 cells that intermingle into adjacent segments encounter cells with higher cyp26b1/c1 expression, which we find is required for downregulation of egr2b expression. Furthermore, egr2b expression is regulated in r2, r4, and r6 by non-autonomous mechanisms that depend upon the number of neighbors that express egr2b. These findings reveal that a community regulation of retinoid signaling maintains homogeneous segmental identity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Determination of the Threshold of Gravity for the Susceptibility to Kinetosis in Fish - a Centrifuge Experiment in the ZARM Drop-Tower employing gradually reduced Gravity

NASA Astrophysics Data System (ADS)

Anken, R.; Hilbig, R.

In the course of earlier experiments at diminished gravity conditions we have successfully used larval cichlid fish Oreochromis mossambicus as a vertebrate model system in investigating the basic cause of susceptibility to motion sickness kinetosis It was observed that most animals of a given batch reveal kinetoses i e performing looping responses LR or spinning movements SM at high quality microgravity 10-6g ZARM drop-tower whereas comparatively few individuals swim kinetotically at low quality microgravity LQM 0 03-0 05g during parabolic aircraft flights Anken and Hilbig Microgravity Sci Technol 15 52-57 2004 In order to gain further insights into a possible threshold of gravity for inducing motion sickness animals were subjected to drop-tower flights within a centrifuge The levels of gravity applied ranged from 0 009g until 0 3g The lowest level of gravity under which few normally swimming fish were observed ranged around 0 015g Since this is a very low level of gravity the normally swimming fish have to be considered to be either extremely sensitive to any force of gravity in order to use it as a cue for postural control or they use cues other than the residual gravity for maintaining equilibrium Most of the remaining kinetotically swimming animals showed LR whereas few exhibited SM With increasing gravity the ratio of normally swimming and spinning specimens increased accompanied by a decrease in the number of looping larvae Regarding the ratio a shift from LR to SM took place at around 0 02g At 0 3g all animals behaved

Antihyperglycaemic potential of the water-ethanol extract of Kalanchoe crenata (Crassulaceae).

PubMed

Kamgang, René; Mboumi, Rostand Youmbi; Fondjo, Angèle Foyet; Tagne, Michel Archange Fokam; N'dillé, Gabriel Patrice Roland Mengue; Yonkeu, Jeanne Ngogang

2008-01-01

Kalanchoe crenata is a vegetable widely used in Cameroon and largely efficient in the treatment of diabetes mellitus. The effect of the water-ethanol extract of this plant (WEKC) on blood glucose levels was investigated in fasting normal and diet-induced diabetic rats (MACAPOS 1) after a short- and medium-term treatment. Diabetes was induced by submitting Wistar rats to a hypercaloric sucrose diet over 4 months. Six hours after a single oral administration of WEKC, 135 and 200 mg kg(-1) body weight extracts significantly (P < 0.01) reduced the blood glucose levels both in normal and diabetic rats without real dose-dependent effect. During the medium-term treatment, 200 mg kg(-1) WEKC administered daily for 4 weeks significantly reduced blood glucose levels within week 1 (P < 0.05), with a maximum effect at week 4 (-52%, P < 0.01), while maintaining glycaemia within the normal range. All the WEKC-treated diabetic rats exhibited significant (P < 0.01) increase in insulin sensitivity index (K (ITT)) compared with the initial time and to the untreated diabetic animals. Animals treated for 4 weeks exhibited a slight resistance in body-weight gain and decrease in food and water intake. The WEKC activities on all parameters assessed were comparable with the glibenclamide effects. Qualitative phytochemical screening revealed that K. crenata contains terpenoids, tannins, polysaccharids, saponins, flavonoids and alkaloids. The data suggest that K. crenata might contain important chemical components that could induce significant improvement in glucose clearance and/or uptake and resistance to body-weight gain and insulin sensitivity, and could be a potent alternative or complementary therapeutic substance in the control of type 2 diabetes and other insulin-resistant conditions.

Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women.

PubMed

Behall, Kay M; Scholfield, Daniel J; Hallfrisch, Judith G; Liljeberg-Elmståhl, Helena G M

2006-05-01

Consumption of a meal high in resistant starch or soluble fiber (beta-glucan) decreases peak insulin and glucose concentrations and areas under the curve (AUCs). The objective was to determine whether the effects of soluble fiber and resistant starch on glycemic variables are additive. Ten normal-weight (43.5 years of age, BMI 22.0 kg/m2) and 10 overweight women (43.3 years of age, BMI 30.4 kg/m2) consumed 10 tolerance meals in a Latin square design. Meals (1 g carbohydrate/kg body wt) were glucose alone or muffins made with different levels of soluble fiber (0.26, 0.68, or 2.3 g beta-glucan/100 g muffin) and three levels of resistant starch (0.71, 2.57, or 5.06 g/100 g muffin). Overweight subjects had plasma insulin concentrations higher than those of normal-weight subjects but maintained similar plasma glucose levels. Compared with low beta-glucan-low resistant starch muffins, glucose and insulin AUC decreased when beta-glucan (17 and 33%, respectively) or resistant starch (24 and 38%, respectively) content was increased. The greatest AUC reduction occurred after meals containing both high beta-glucan-high resistant starch (33 and 59% lower AUC for glucose and insulin, respectively). Overweight women were somewhat more insulin resistant than control women. Soluble fiber appears to have a greater effect on postprandial insulin response while glucose reduction is greater after resistant starch from high-amylose cornstarch. The reduction in glycemic response was enhanced by combining resistant starch and soluble fiber. Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism in both normal and overweight women.

Ectopic expression of ABSCISIC ACID 2/GLUCOSE INSENSITIVE 1 in Arabidopsis promotes seed dormancy and stress tolerance.

PubMed

Lin, Pei-Chi; Hwang, San-Gwang; Endo, Akira; Okamoto, Masanori; Koshiba, Tomokazu; Cheng, Wan-Hsing

2007-02-01

Abscisic acid (ABA) is an important phytohormone that plays a critical role in seed development, dormancy, and stress tolerance. 9-cis-Epoxycarotenoid dioxygenase is the key enzyme controlling ABA biosynthesis and stress tolerance. In this study, we investigated the effect of ectopic expression of another ABA biosynthesis gene, ABA2 (or GLUCOSE INSENSITIVE 1 [GIN1]) encoding a short-chain dehydrogenase/reductase in Arabidopsis (Arabidopsis thaliana). We show that ABA2-overexpressing transgenic plants with elevated ABA levels exhibited seed germination delay and more tolerance to salinity than wild type when grown on agar plates and/or in soil. However, the germination delay was abolished in transgenic plants showing ABA levels over 2-fold higher than that of wild type grown on 250 mm NaCl. The data suggest that there are distinct mechanisms underlying ABA-mediated inhibition of seed germination under diverse stress. The ABA-deficient mutant aba2, with a shorter primary root, can be restored to normal root growth by exogenous application of ABA, whereas transgenic plants overexpressing ABA2 showed normal root growth. The data reflect that the basal levels of ABA are essential for maintaining normal primary root elongation. Furthermore, analysis of ABA2 promoter activity with ABA2::beta-glucuronidase transgenic plants revealed that the promoter activity was enhanced by multiple prolonged stresses, such as drought, salinity, cold, and flooding, but not by short-term stress treatments. Coincidently, prolonged drought stress treatment led to the up-regulation of ABA biosynthetic and sugar-related genes. Thus, the data support ABA2 as a late expression gene that might have a fine-tuning function in mediating ABA biosynthesis through primary metabolic changes in response to stress.

Functions of transmembrane domain 3 of human melanocortin-4 receptor.

PubMed

Mo, Xiu-Lei; Yang, Rui; Tao, Ya-Xiong

2012-12-01

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor critical for maintaining energy homeostasis. Transmembrane domain 3 (TM3) of MC4R contains residues that were suggested to be essential in ligand binding and signaling. Several MC4R mutations in TM3 are associated with human obesity. To gain a better understanding of the functions of TM3, we analyzed the functions of 26 residues in TM3 using alanine-scanning mutagenesis. We showed that all mutants had normal cell-surface expression. Four mutants were defective in ligand binding and signaling and six mutants had normal ligand binding but impaired cAMP production. L140A had increased basal cAMP level. To further characterize the function of L140, we generated 17 additional L140 mutants. Fifteen L140 mutants had significantly decreased cell-surface expression, with L140R and L140V expressed normally. Ten L140 mutants had increased basal cAMP activities. Four L140 mutants were defective in ligand-stimulated cAMP generation. Interestingly, with the ERK1/2 pathway, we showed that nine constitutively active mutants had similar levels of basal pERK1/2 as that of WT, and two signaling defective mutants had similar levels of pERK1/2 as that of WT upon agonist stimulation, different from their cAMP signaling properties, suggesting biased signaling in these mutant receptors. In summary, we identified 13 residues in TM3 that were essential for ligand binding and/or signaling. Moreover, L140 was critical for locking MC4R in inactive conformation and several mutants showed biased signaling in cAMP and ERK1/2 signaling pathways.

Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine

PubMed Central

Faller, Kiterie M E; Atzler, Dorothee; McAndrew, Debra J; Zervou, Sevasti; Whittington, Hannah J; Simon, Jillian N; Aksentijevic, Dunja; ten Hove, Michiel; Choe, Chi-un; Isbrandt, Dirk; Casadei, Barbara; Schneider, Jurgen E; Neubauer, Stefan; Lygate, Craig A

2018-01-01

Abstract Aims Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. Methods and results Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. Conclusions Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases. PMID:29236952

Obese adults have visual attention bias for food cue images: evidence for altered reward system function.

PubMed

Castellanos, E H; Charboneau, E; Dietrich, M S; Park, S; Bradley, B P; Mogg, K; Cowan, R L

2009-09-01

The major aim of this study was to investigate whether the motivational salience of food cues (as reflected by their attention-grabbing properties) differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity. A total of 18 obese and 18 normal-weight, otherwise healthy, adult women between the ages of 18 and 35 participated in an eye-tracking paradigm in combination with a visual probe task. Eye movements and reaction time to food and non-food images were recorded during both fasted and fed conditions in a counterbalanced design. Eating behavior and hunger level were assessed by self-report measures. Obese individuals had higher scores than normal-weight individuals on self-report measures of responsiveness to external food cues and vulnerability to disruptions in control of eating behavior. Both obese and normal-weight individuals demonstrated increased gaze duration for food compared to non-food images in the fasted condition. In the fed condition, however, despite reduced hunger in both groups, obese individuals maintained the increased attention to food images, whereas normal-weight individuals had similar gaze duration for food and non-food images. Additionally, obese individuals had preferential orienting toward food images at the onset of each image. Obese and normal-weight individuals did not differ in reaction time measures in the fasted or fed condition. Food cue incentive salience is elevated equally in normal-weight and obese individuals during fasting. Obese individuals retain incentive salience for food cues despite feeding and decreased self-report of hunger. Sensitization to food cues in the environment and their dysregulation in obese individuals may play a role in the development and/or maintenance of obesity.

Levels-Of-Processing Effect on Word Recognition in Schizophrenia

PubMed Central

Ragland, J. Daniel; Moelter, Stephen T.; McGrath, Claire; Hill, S. Kristian; Gur, Raquel E.; Bilker, Warren B.; Siegel, Steven J.; Gur, Ruben C.

2015-01-01

Background Individuals with schizophrenia have difficulty organizing words semantically to facilitate encoding. This is commonly attributed to organizational rather than semantic processing limitations. By requiring participants to classify and encode words on either a shallow (e.g., uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of-processing paradigm eliminates the need to generate organizational strategies. Methods This paradigm was administered to 30 patients with schizophrenia and 30 healthy comparison subjects to test whether providing a strategy would improve patient performance. Results Word classification during shallow and deep encoding was slower and less accurate in patients. Patients also responded slowly during recognition testing and maintained a more conservative response bias following deep encoding; however, both groups showed a robust levels-of-processing effect on recognition accuracy, with unimpaired patient performance following both shallow and deep encoding. Conclusions This normal levels-of-processing effect in the patient sample suggests that semantic processing is sufficiently intact for patients to benefit from organizational cues. Memory remediation efforts may therefore be most successful if they focus on teaching patients to form organizational strategies during initial encoding. PMID:14643082

Levels-of-processing effect on word recognition in schizophrenia.

PubMed

Ragland, J Daniel; Moelter, Stephen T; McGrath, Claire; Hill, S Kristian; Gur, Raquel E; Bilker, Warren B; Siegel, Steven J; Gur, Ruben C

2003-12-01

Individuals with schizophrenia have difficulty organizing words semantically to facilitate encoding. This is commonly attributed to organizational rather than semantic processing limitations. By requiring participants to classify and encode words on either a shallow (e.g., uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of-processing paradigm eliminates the need to generate organizational strategies. This paradigm was administered to 30 patients with schizophrenia and 30 healthy comparison subjects to test whether providing a strategy would improve patient performance. Word classification during shallow and deep encoding was slower and less accurate in patients. Patients also responded slowly during recognition testing and maintained a more conservative response bias following deep encoding; however, both groups showed a robust levels-of-processing effect on recognition accuracy, with unimpaired patient performance following both shallow and deep encoding. This normal levels-of-processing effect in the patient sample suggests that semantic processing is sufficiently intact for patients to benefit from organizational cues. Memory remediation efforts may therefore be most successful if they focus on teaching patients to form organizational strategies during initial encoding.

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity.

PubMed

O'Brien, William G; Berka, Vladimir; Tsai, Ah-Lim; Zhao, Zhaoyang; Lee, Cheng Chi

2015-08-07

Erythrocytes are the key target in 5'-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3(-/-) mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

Surviving starvation: essential role of the ghrelin-growth hormone axis.

PubMed

Goldstein, J L; Zhao, T-j; Li, R L; Sherbet, D P; Liang, G; Brown, M S

2011-01-01

After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Mice were fed 40% of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23 h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60 mg/dL. In Goat(-/-) mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20 mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.

Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence

PubMed Central

Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

2016-01-01

We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [11C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [11C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [11C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [11C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication. PMID:26321315

Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence.

PubMed

Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

2016-03-01

We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [(11)C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [(11)C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication.

Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma.

PubMed

Iizuka, Norio; Hazama, Shoichi; Yoshimura, Kiyoshi; Yoshino, Shigefumi; Tangoku, Akira; Miyamoto, Koji; Okita, Kiwamu; Oka, Masaaki

2002-05-10

We previously showed that the natural herb Coptidis rhizoma has an anticachectic effect in nude mice bearing human esophageal cancer cells. We further investigated this phenomenon by examining the anticachectic effect of C. rhizoma in syngeneic mice bearing colon 26/clone 20 carcinoma cells, which cause IL-6-related cachexia after cell injection. We evaluated nutritional parameters such as serum glucose level and wasting of adipose tissue and muscle in tumor-bearing and non-tumor-bearing mice treated with C. rhizoma (CR) supplement or a normal diet. IL-6 levels in those mice were quantified by ELISA and real-time RT-PCR. CR supplementation significantly attenuated weight loss in tumor-bearing mice without changing food intake or tumor growth. Furthermore, these mice maintained good nutritional status. IL-6 mRNA levels in tumors and spleens and IL-6 protein levels in tumors and sera were significantly lower in tumor-bearing mice treated with CR supplement than in those treated with a normal diet. CR supplementation did not affect food intake, body weight, nutritional parameters and IL-6 levels in non-tumor-bearing mice. An in vitro study showed that C. rhizoma and its major component, berberine, inhibited IL-1-induced IL-6 mRNA expression in a dose-dependent manner in colon 26/clone 20 cells. Our results showed that C. rhizoma exerts an anticachectic effect on colon 26/clone 20-transplanted mice and that its effect is associated with tumor IL-6 production. We also suggest that its effect might be due to berberine. Copyright 2002 Wiley-Liss, Inc.

Seismic risk management solution for nuclear power plants

DOE PAGES

Coleman, Justin; Sabharwall, Piyush

2014-12-01

Nuclear power plants should safely operate during normal operations and maintain core-cooling capabilities during off-normal events, including external hazards (such as flooding and earthquakes). Management of external hazards to expectable levels of risk is critical to maintaining nuclear facility and nuclear power plant safety. Seismic risk is determined by convolving the seismic hazard with seismic fragilities (capacity of systems, structures, and components). Seismic isolation (SI) is one protective measure showing promise to minimize seismic risk. Current SI designs (used in commercial industry) reduce horizontal earthquake loads and protect critical infrastructure from the potentially destructive effects of large earthquakes. The benefitmore » of SI application in the nuclear industry is being recognized and SI systems have been proposed in American Society of Civil Engineer Standard 4, ASCE-4, to be released in the winter of 2014, for light water reactors facilities using commercially available technology. The intent of ASCE-4 is to provide criteria for seismic analysis of safety related nuclear structures such that the responses to design basis seismic events, computed in accordance with this standard, will have a small likelihood of being exceeded. The U.S. nuclear industry has not implemented SI to date; a seismic isolation gap analysis meeting was convened on August 19, 2014, to determine progress on implementing SI in the U.S. nuclear industry. The meeting focused on the systems and components that could benefit from SI. As a result, this article highlights the gaps identified at this meeting.« less

The role of p38 in mitochondrial respiration in male and female mice.

PubMed

Ju, Xiaohua; Wen, Yi; Metzger, Daniel; Jung, Marianna

2013-06-07

p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38(loxP/loxP) mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: Evidence from human psychophysics, animal models, and neuroimaging

PubMed Central

Price, Donald D.; Craggs, Jason G.; Zhou, QiQi; Verne, G. Nicholas; Perlstein, William M.; Robinson, Michael E.

2010-01-01

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that is often accompanied by both visceral and somatic hyperalgesia (enhanced pain from colorectal and somatic stimuli). Neural mechanisms of both types of hyperalgesia have been analyzed by neuroimaging studies of IBS patients and animal analog studies of “IBS-like” rats with delayed rectal and somatic hypersensitivity. Results from these studies suggest that pains associated with both visceral and widespread secondary cutaneous hyperalgesia are dynamically maintained by tonic impulse input from the non-inflamed colon and/or rectum and by brain-to-spinal cord facilitation. Enhanced visceral and somatic pains are accompanied by enhanced pain-related brain activity in IBS patients as compared to normal control subjects; placebos can normalize both their hyperalgesia and enhanced brain activity. That pain in IBS which is likely to be at least partly maintained by peripheral impulse input from the colon/rectum is supported by results showing that local rectal–colonic anesthesia normalizes visceral and somatic hyperalgesia in IBS patients and visceral and somatic hypersensitivity in “IBS-like” rats. Yet these forms of hyperalgesia are also highly modifiable by placebo and nocebo factors (e.g., expectations of relief or distress, respectively). Our working hypothesis is that synergistic interactions occur between placebo/nocebo factors and enhanced afferent processing so as to enhance, maintain, or reduce hyperalgesia in IBS. This explanatory model may be relevant to other persistent pain conditions. PMID:19375508

78 FR 30913 - ALLETE, Inc.; Notice of Application for Temporary Amendment of License and Soliciting Comments...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

....5 feet from the normal reservoir elevation of 1177.0 feet on December 17, 2012. The applicant proposes to maintain the elevation within 0.25 feet of 1175.5 feet under normal operations until spillway repairs are completed, and the reservoir is refilled. As currently planned, the reservoir will be refilled...

Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests.

PubMed

Otsuka, Hiroki; Sasai, Hideo; Abdelkreem, Elsayed; Kawamoto, Norio; Kawamoto, Minako; Kamiya, Toshiya; Tanimoto, Yasuo; Kikuchi, Atsuo; Kure, Shigeo; Numakura, Chikahiko; Hayasaka, Kiyoshi; Fukao, Toshiyuki

2016-12-01

Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD + ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.

Quantitative implementation of the endogenous molecular-cellular network hypothesis in hepatocellular carcinoma.

PubMed

Wang, Gaowei; Zhu, Xiaomei; Gu, Jianren; Ao, Ping

2014-06-06

A quantitative hypothesis for cancer genesis and progression-the endogenous molecular-cellular network hypothesis, intended to include both genetic and epigenetic causes of cancer-has been proposed recently. Using this hypothesis, here we address the molecular basis for maintaining normal liver and hepatocellular carcinoma (HCC), and the potential strategy to cure or relieve HCC. First, we elaborate the basic assumptions of the hypothesis and establish a core working network of HCC according to the hypothesis. Second, we quantify the working network by a nonlinear dynamical system. We show that the working network reproduces the main known features of normal liver and HCC at both the modular and molecular levels. Lastly, the validated working network reveals that (i) specific positive feedback loops are responsible for the maintenance of normal liver and HCC; (ii) inhibiting proliferation and inflammation-related positive feedback loops and simultaneously inducing a liver-specific positive feedback loop is predicated as a potential strategy to cure or relieve HCC; and (iii) the genesis and regression of HCC are asymmetric. In light of the characteristic properties of the nonlinear dynamical system, we demonstrate that positive feedback loops must exist as a simple and general molecular basis for the maintenance of heritable phenotypes, such as normal liver and HCC, and regulating the positive feedback loops directly or indirectly provides potential strategies to cure or relieve HCC.

Specificity and timescales of cortical adaptation as inferences about natural movie statistics.

PubMed

Snow, Michoel; Coen-Cagli, Ruben; Schwartz, Odelia

2016-10-01

Adaptation is a phenomenological umbrella term under which a variety of temporal contextual effects are grouped. Previous models have shown that some aspects of visual adaptation reflect optimal processing of dynamic visual inputs, suggesting that adaptation should be tuned to the properties of natural visual inputs. However, the link between natural dynamic inputs and adaptation is poorly understood. Here, we extend a previously developed Bayesian modeling framework for spatial contextual effects to the temporal domain. The model learns temporal statistical regularities of natural movies and links these statistics to adaptation in primary visual cortex via divisive normalization, a ubiquitous neural computation. In particular, the model divisively normalizes the present visual input by the past visual inputs only to the degree that these are inferred to be statistically dependent. We show that this flexible form of normalization reproduces classical findings on how brief adaptation affects neuronal selectivity. Furthermore, prior knowledge acquired by the Bayesian model from natural movies can be modified by prolonged exposure to novel visual stimuli. We show that this updating can explain classical results on contrast adaptation. We also simulate the recent finding that adaptation maintains population homeostasis, namely, a balanced level of activity across a population of neurons with different orientation preferences. Consistent with previous disparate observations, our work further clarifies the influence of stimulus-specific and neuronal-specific normalization signals in adaptation.

Specificity and timescales of cortical adaptation as inferences about natural movie statistics

PubMed Central

Snow, Michoel; Coen-Cagli, Ruben; Schwartz, Odelia

2016-01-01

Adaptation is a phenomenological umbrella term under which a variety of temporal contextual effects are grouped. Previous models have shown that some aspects of visual adaptation reflect optimal processing of dynamic visual inputs, suggesting that adaptation should be tuned to the properties of natural visual inputs. However, the link between natural dynamic inputs and adaptation is poorly understood. Here, we extend a previously developed Bayesian modeling framework for spatial contextual effects to the temporal domain. The model learns temporal statistical regularities of natural movies and links these statistics to adaptation in primary visual cortex via divisive normalization, a ubiquitous neural computation. In particular, the model divisively normalizes the present visual input by the past visual inputs only to the degree that these are inferred to be statistically dependent. We show that this flexible form of normalization reproduces classical findings on how brief adaptation affects neuronal selectivity. Furthermore, prior knowledge acquired by the Bayesian model from natural movies can be modified by prolonged exposure to novel visual stimuli. We show that this updating can explain classical results on contrast adaptation. We also simulate the recent finding that adaptation maintains population homeostasis, namely, a balanced level of activity across a population of neurons with different orientation preferences. Consistent with previous disparate observations, our work further clarifies the influence of stimulus-specific and neuronal-specific normalization signals in adaptation. PMID:27699416

Ontogenetic, gravity-dependent development of rat soleus muscle

NASA Technical Reports Server (NTRS)

Ohira, Y.; Tanaka, T.; Yoshinaga, T.; Kawano, F.; Nomura, T.; Nonaka, I.; Allen, D. L.; Roy, R. R.; Edgerton, V. R.

2001-01-01

We tested the hypothesis that rat soleus muscle fiber growth and changes in myosin phenotype during the postnatal, preweaning period would be largely independent of weight bearing. The hindlimbs of one group of pups were unloaded intermittently from postnatal day 4 to day 21: the pups were isolated from the dam for 5 h during unloading and returned for nursing for 1 h. Control pups were either maintained with the dam as normal or put on an alternating feeding schedule as described above. The enlargement of mass (approximately 3 times), increase in myonuclear number (approximately 1.6 times) and myonuclear domain (approximately 2.6 times), and transformation toward a slow fiber phenotype (from 56 to 70% fibers expressing type I myosin heavy chain) observed in controls were inhibited by hindlimb unloading. These properties were normalized to control levels or higher within 1 mo of reambulation beginning immediately after the unloading period. Therefore, chronic unloading essentially stopped the ontogenetic developmental processes of 1) net increase in DNA available for transcription, 2) increase in amount of cytoplasm sustained by that DNA pool, and 3) normal transition of myosin isoforms that occur in some fibers from birth to weaning. It is concluded that normal ontogenetic development of a postural muscle is highly dependent on the gravitational environment even during the early postnatal period, when full weight-bearing activity is not routine.

The Genetics and Epigenetics of Kidney Development

PubMed Central

Patel, Sanjeevkumar R.; Dressler, Gregory R.

2013-01-01

The development of the mammalian kidney has been studied at the genetic, biochemical, and cell biological level for more than 40 years. As such, detailed mechanisms governing early patterning, cell lineages, and inductive interactions are well described. How genes interact to specify the renal epithelial cells of the nephrons and how this specification is relevant to maintaining normal renal function is discussed. Implicit in the development of the kidney are epigenetic mechanisms that mark renal cell types and connect certain developmental regulatory factors to chromatin modifications that control gene expression patterns and cellular physiology. In adults, such regulatory factors and their epigenetic pathways may function in regeneration and may be disturbed in disease processes. PMID:24011574

Hepatic delta 6-desaturase activity in lean and genetically obese ob/ob mice.

PubMed Central

Hughes, S; York, D A

1985-01-01

Hepatic delta 6-desaturase activity is primarily located in the mitochondrial fraction in mice. Both delta 6- and delta 5-desaturase activities are increased in the liver of young (6-week-old) obese mice. The increase in hepatic delta 6-desaturase activity in obese mice does not occur until weaning. Neither restriction of food intake nor hyperinsulinaemia normalize hepatic delta 6-desaturase activity of obese mice. Both cold acclimation and tri-iodothyronine (30 micrograms/day per kg) decreased hepatic delta 6-desaturase activity of obese mice to levels observed in lean mice, whereas the increase in activity in obese mice was still maintained after the induction of hypothyroidism. PMID:3977836

Disruption of striatal-enriched protein tyrosine phosphatase (STEP) function in neuropsychiatric disorders

PubMed Central

Karasawa, Takatoshi; Lombroso, Paul J.

2014-01-01

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific tyrosine phosphatase that plays a major role in the development of synaptic plasticity. Recent findings have implicated STEP in several psychiatric and neurological disorders, including Alzheimer’s disease, schizophrenia, fragile X syndrome, Huntington’s disease, stroke/ischemia, and stress-related psychiatric disorders. In these disorders, STEP protein expression levels and activity are dysregulated, contributing to the cognitive deficits that are present. In this review, we focus on the most recent findings on STEP, discuss how STEP expression and activity are maintained during normal cognitive function, and how disruptions in STEP activity contribute to a number of illnesses. PMID:25218562

Normal morphogenesis of epithelial tissues and progression of epithelial tumors

PubMed Central

Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

2011-01-01

Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

Primary lymphangiectasia in a dingo (Canis familiaris dingo).

PubMed

Suedmeyer, Wm Kirk; Ludlow, Chris; Layton, Candace; Dennis, Jeff; Miller, Margaret

2004-12-01

A 3-yr-old intact male dingo (Canis familiaris dingo) presented with a 3-mo history of diarrhea. The diarrhea did not resolve with antibiotics or intestinal protectants. Fecal examination for parasites, fecal cultures, physical examination, and radiographs were unremarkable. Enteroscopic duodenal biopsies showed dilated lacteals without inflammation. Results of serum folate, cobalamin, and trypsin-like immunoreactivity were normal. Low serum total protein and albumin combined with increased fecal levels of alpha-1 protease inhibitor suggested the diagnosis of lymphangiectasia. Full-thickness intestinal biopsies of the duodenum, jejunum, and ileum revealed dilated mucosal and submucosal lacteals without associated inflammation, confirming the diagnosis of primary lymphangiectasia. Currently, the dingo is being maintained with nutritional management.

Table of superdeformed nuclear bands and fission isomers (from Nuclear Data Sheets, v.78, issue 1, May 1996)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, B.; Firestone, R B.; Chu, S Y.F.

As part of a committment to maintain nuclear structure data as current as possible in the Evaluated Nuclear Structure Data File (ENSDF) and the Table of Isotopes, the author have been updating the information on superdeformed and hyperdeformed nuclear bands. As of February, 1996, they have compiled data for 161 superdeformed bands and 47 fission isomers identified in 93 nuclides for this publication. This is an increase of 75 superdeformed bands and 20 new nuclides since the first edition in 1994. Partial data for superdeformed bands and fission isomers are shown in the band drawings. For each nuclide there ismore » a complete level table listing both normal (taken from the ENSDF file) and superdeformed band assignments; level energy, spin, parity, half-life, magnetic moments, decay branchings; and the energies, final levels, relative intensities, multipolarities, and mixing ratios for transitions deexciting each level. Mass excess, decay energies, and proton and neutron separation energies are also provided from the evaluation of Audi and Wapstra. For superdeformed and hyperdeformed bands they provide the following quantities: level energies; level half-lives; level spins; and gamma ray energies.« less

Cost-effectiveness of Maintaining Daily Intake of Oat β-Glucan for Coronary Heart Disease Primary Prevention.

PubMed

Earnshaw, Stephanie R; McDade, Cheryl L; Chu, YiFang; Fleige, Lisa E; Sievenpiper, John L

2017-04-01

Oat β-glucan reduces cholesterol levels and thus reduces the risk for coronary heart disease (CHD). However, its economic impact has not been well studied. We examined the economic impact of daily intake of ≥3 g of oat β-glucan in primary prevention of CHD in patients receiving statins or no pharmacologic treatment. A decision model was developed to compare costs and outcomes associated with lowering cholesterol levels with no pharmacologic treatment and normal diet, no pharmacologic treatment plus ≥3 g/d of oat β-glucan, and statin therapy plus ≥3 g/d of oat β-glucan. The population comprised men 45, 55, or 65 years of age with no history of cardiovascular disease and a 10-year risk for CHD of 5%, 7.5%, or 10%. Clinical efficacy data were gathered from meta-analyses; safety data, costs, and utilities were gathered from published literature. Cost per quality-adjusted life years and number of first events were reported. Maintaining ≥3 g/d of β-glucan may be cost-effective in men aged 45, 55, and 65 years with 10-year CHD risks of 5.0%, 7.5%, and 10.0% taking no pharmacologic treatment or on statins. It may also reduce first events of myocardial infarction and CHD death. Results are sensitive to oat β-glucan cost but insensitive to changes in other parameters. Maintaining ≥3 g of oat β-glucan daily remains cost-effective within plausible range of values. β-glucan may be cost-effective for preventing CHD events in middle-aged men with no history of cardiovascular events whose 10-year CHD risk is ≥5%. Maintaining daily β-glucan intake may have considerable impact on first events. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Analysis of DNA methylation level by methylation-sensitive amplification polymorphism in half smooth tongue sole ( Cynoglossus semilaevis) subjected to salinity stress

NASA Astrophysics Data System (ADS)

Li, Siping; He, Feng; Wen, Haishen; Li, Jifang; Si, Yufeng; Liu, Mingyuan; He, Huiwen; Huang, Zhengju

2017-04-01

Increasingly arisen environmental constraints may contribute to heritable phenotypic variation including methylation changes, which can help the animals with development, growth and survival. In this study, we assessed the DNA methylation levels in three tissues (gonad, kidney and gill) of half smooth tongue sole under the salinity stress. The methylation-sensitive amplification polymorphism (MSAP) technique was applied to illustrate the regulation of epigenetic mechanism in environmental stimuli. Fish were subjected to 15 salinity treatment for 7 and 60 days, respectively. A total of 11259 fragments were amplified with 8 pairs of selective primers. The levels of methylated DNA in different tissues of females and males without salinity stress were analyzed, which were 32.76% and 47.32% in gonad; 38.13% and 37.69% in kidney; 37.58% and 34.96% in gill, respectively. In addition, the significant difference was observed in gonad between females and males, indicating that discrepant regulation in gonadal development and differentiation may involve sex-related genes. Further analysis showed that total and hemi-methylation were significantly decreased under 15 salinity for 7 days, probably resulting in up-regulating salt-tolerance genes expression to adjust salt changing. With the adjustment for 60 days, total and hemi-methylation prominently went back to its normal levels to obtain equilibrium. Particularly, full methylation levels were steady along with salinity stress to maintain the stability of gene expression. Additionally, the data showed that gonads in females and gills in males were superior in adaptability. As a result, DNA methylation regulates tissue- specific epiloci, and may respond to salinity stress by regulating gene expression to maintain animal survival and activity.

Thioredoxin-deficient mice, a novel phenotype sensitive to ambient air and hypersensitive to hyperoxia-induced lung injury

PubMed Central

2014-01-01

Pulmonary oxygen toxicity is a major clinical problem for patients undergoing supplemental oxygen therapy. Thioredoxin (Trx) is an endogenous antioxidant protein that regenerates oxidatively inactivated proteins. We examined how Trx contributes to oxygen tolerance by creating transgenic mice with decreased levels of functional thioredoxin (dnTrx-Tg) using a dominant-negative approach. These mice showed decreased Trx activity in the lung although the expression of mutant protein is three times higher than the wild-type mice. Additionally, we found that these mice showed increased oxidation of endogenous Trx in room air. When exposed to hyperoxia (>90% O2) for 4 days, they failed to recover and showed significant mortality. Even in normal oxygen levels, these mice displayed a significant decrease in aconitase and NADH dehydrogenase activities, decreased mitochondrial energy metabolism, increased p53 and Gadd45α expression, and increased synthesis of proinflammatory cytokines. These effects were further increased by hyperoxia. We also generated mice overexpressing Trx (Trx-Tg) and found they maintained lung redox balance during exposure to high oxygen and thus were resistant to hyperoxia-induced lung injury. These mice had increased levels of reduced Trx in the lung in normoxia as well as hyperoxia. Furthermore, the levels of aconitase and NADH dehydrogenase activities were maintained in these mice concomitant with maintenance of mitochondrial energy metabolism. The genotoxic stress markers such as p53 or Gadd45α remained in significantly lower levels in hyperoxia compared with dnTrx-Tg or wild-type mice. These studies establish that mice deficient in functional Trx exhibit a phenotype of sensitivity to ambient air and hypersensitivity to hyperoxia. PMID:25539854

Continuous plutonium dissolution apparatus

DOEpatents

Meyer, F.G.; Tesitor, C.N.

1974-02-26

This invention is concerned with continuous dissolution of metals such as plutonium. A high normality acid mixture is fed into a boiler vessel, vaporized, and subsequently condensed as a low normality acid mixture. The mixture is then conveyed to a dissolution vessel and contacted with the plutonium metal to dissolve the plutonium in the dissolution vessel, reacting therewith forming plutonium nitrate. The reaction products are then conveyed to the mixing vessel and maintained soluble by the high normality acid, with separation and removal of the desired constituent. (Official Gazette)

Monitoring ATP dynamics in electrically active white matter tracts

PubMed Central

Trevisiol, Andrea; Saab, Aiman S; Winkler, Ulrike; Marx, Grit; Imamura, Hiromi; Möbius, Wiebke; Kusch, Kathrin; Nave, Klaus-Armin; Hirrlinger, Johannes

2017-01-01

In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders. DOI: http://dx.doi.org/10.7554/eLife.24241.001 PMID:28414271

Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism.

PubMed

Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Gómez-Ambrosi, Javier; Frago, Laura M; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

2015-11-05

Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Real-time distributed fiber optic sensor for security systems: Performance, event classification and nuisance mitigation

NASA Astrophysics Data System (ADS)

Mahmoud, Seedahmed S.; Visagathilagar, Yuvaraja; Katsifolis, Jim

2012-09-01

The success of any perimeter intrusion detection system depends on three important performance parameters: the probability of detection (POD), the nuisance alarm rate (NAR), and the false alarm rate (FAR). The most fundamental parameter, POD, is normally related to a number of factors such as the event of interest, the sensitivity of the sensor, the installation quality of the system, and the reliability of the sensing equipment. The suppression of nuisance alarms without degrading sensitivity in fiber optic intrusion detection systems is key to maintaining acceptable performance. Signal processing algorithms that maintain the POD and eliminate nuisance alarms are crucial for achieving this. In this paper, a robust event classification system using supervised neural networks together with a level crossings (LCs) based feature extraction algorithm is presented for the detection and recognition of intrusion and non-intrusion events in a fence-based fiber-optic intrusion detection system. A level crossings algorithm is also used with a dynamic threshold to suppress torrential rain-induced nuisance alarms in a fence system. Results show that rain-induced nuisance alarms can be suppressed for rainfall rates in excess of 100 mm/hr with the simultaneous detection of intrusion events. The use of a level crossing based detection and novel classification algorithm is also presented for a buried pipeline fiber optic intrusion detection system for the suppression of nuisance events and discrimination of intrusion events. The sensor employed for both types of systems is a distributed bidirectional fiber-optic Mach-Zehnder (MZ) interferometer.

Hepcidin expression does not rescue the iron-poor phenotype of Kupffer cells in Hfe-null mice after liver transplantation.

PubMed

Garuti, Cinzia; Tian, Yinghua; Montosi, Giuliana; Sabelli, Manuela; Corradini, Elena; Graf, Rolf; Ventura, Paolo; Vegetti, Alberto; Clavien, Pierre-Alain; Pietrangelo, Antonello

2010-07-01

Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver-the source of the iron regulatory hormone hepcidin-in pathogenesis in mice. We exchanged livers between Hfe wild-type (+/+) and Hfe null (-/-) mice by orthotopic liver transplantation (OLT) and assessed histopathology, serum and tissue iron parameters, and hepatic hepcidin messenger RNA expression. At 6-8 months after OLT, Hfe(-/-) mice that received Hfe(-/-) livers maintained the hemochromatosis phenotype: iron accumulation in hepatocytes but not Kupffer cells (KC), increased transferrin levels, and low levels of iron in the spleen. Hfe(+/+) mice that received Hfe(-/-) livers had increased levels of iron in serum and liver and low levels of iron in spleen. However, they did not develop the iron-poor KCs that characterize hemochromatosis: KCs appeared iron rich, although hepatic hepcidin expression was low. Transplantation of Hfe(+/+) livers into Hfe(-/-) mice prevented hepatic iron accumulation but did not return spleen and plasma levels of iron to normal; KCs still appeared to be iron poor, despite normal hepcidin expression. In Hfe(-/-) mice, transplantation of livers from Hfe(+/+) mice reversed the iron-loading phenotype associated with hemochromatosis (regardless of Hfe expression in intestine). However, KCs still had low levels of iron that were not affected by hepatic hepcidin expression. These findings indicate an independent, iron-modifying effect of HFE in KCs. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Vitamin D levels in children with severe hemophilia A: an underappreciated deficiency.

PubMed

Albayrak, Canan; Albayrak, Davut

2015-04-01

Osteoporosis in hemophilic patients is a significant problem. The causes of osteoporosis in hemophilic patients are lack of adequate exercise, multiple hemorrhage and inflammation, and low vitamin D levels. The aim of this study was to retrospectively determine the frequency of vitamin D deficiency and insufficiency in children with severe hemophilia A. Forty-seven children with severe hemophilia were included in the study. None of the patients had previously received vitamin D supplementation. No patient had clinical or radiologic findings of rickets or seropositivity of hepatitis C virus or HIV. The mean age of the patients was 11.64 ± 5.70 (range, 2-18) years. The mean vitamin D level was 16.35 ± 7.49 ng/ml (range, 3.25-33.80). Vitamin D levels were below 10 ng/ml (severe vitamin D deficiency) in 9 cases (19%), between 10 and 19.99 ng/ml (vitamin D deficiency) in 23 cases (49%), between 20 and 29.99 ng/ml (vitamin D insufficiency) in 13 cases (28%), and above 30 ng/ml (normal vitamin D level) in 2 cases (4%). The mean serum levels of 25-hydroxy vitamin D in the children with hemophilia during winter and autumn were significantly lower than that during summer (P = 0.0028 and P = 0.0091, respectively). A majority of our hemophilic patients (96%) had low vitamin D levels. The study showed that the risk of vitamin D deficiency is the most highest during winter and autumn. Normal lifelong vitamin D levels are especially important in hemophilia because of the possible synergistic effect of vitamin D levels on periarticular and general osteoporosis, which is intrinsic to hemophilic conditions. We advise routine checking of vitamin D levels twice a year and vitamin D supplementation to maintain its level between 30 and 100 ng/ml.

Exploratory Development of an Ultrafast-Curing Wound Dressing

DTIC Science & Technology

1988-11-30

removed at will. 0 Control water vapor and oxygen exchange, thus maintaining a moist environment for rapid healing. * Gradually deliver broad-spectrum...removal without precipitating another bjeeding episode, (c) promotion of normal wound healing under moist , aseptic environment, and (d) prevention of...conditions, the field dressing is capable of maintaining the wound moist , but aseptic. And, as explained in the following paragraphs, it is ncm

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data.

PubMed

Li, Xiaohong; Brock, Guy N; Rouchka, Eric C; Cooper, Nigel G F; Wu, Dongfeng; O'Toole, Timothy E; Gill, Ryan S; Eteleeb, Abdallah M; O'Brien, Liz; Rai, Shesh N

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level.

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data

PubMed Central

Li, Xiaohong; Brock, Guy N.; Rouchka, Eric C.; Cooper, Nigel G. F.; Wu, Dongfeng; O’Toole, Timothy E.; Gill, Ryan S.; Eteleeb, Abdallah M.; O’Brien, Liz

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level. PMID:28459823

Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance.

PubMed

Suchy, James; Chan, Amy; Shea, Thomas B

2009-01-01

Alzheimer disease has a complex etiology composed of nutritional and genetic risk factors and predispositions. Moreover, genetic risk factors for cognitive decline may remain latent pending age-related decline in nutrition, suggesting the potential importance of early nutritional intervention, including preventative approaches. We hypothesized that a combination of multiple nutritional additives may be able to provide neuroprotection. We demonstrate herein that dietary supplementation with a mixture of ALA, ALCAR, GPC, DHA, and PS reduced reactive oxygen species in normal mice by 57% and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet. We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

PubMed Central

West, John D; Dorà, Natalie J; Collinson, J Martin

2015-01-01

In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis. PMID:25815115

Propafenone

MedlinePlus

... arrhythmia (irregular heartbeat) and to maintain a normal heart rate. Propafenone is in a class of medications called antiarrhythmics. It works by acting on the heart muscle to improve the heart's rhythm.

Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter

PubMed Central

Stahon, Katharine E.; Bastian, Chinthasagar; Griffith, Shelby; Kidd, Grahame J.; Brunet, Sylvain

2016-01-01

The impact of aging on CNS white matter (WM) is of general interest because the global effects of aging on myelinated nerve fibers are more complex and profound than those in cortical gray matter. It is important to distinguish between axonal changes created by normal aging and those caused by neurodegenerative diseases, including multiple sclerosis, stroke, glaucoma, Alzheimer's disease, and traumatic brain injury. Using three-dimensional electron microscopy, we show that in mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicker myelin, and are characterized by longer and thicker mitochondria, which are associated with altered levels of mitochondrial shaping proteins. These structural alterations in aging mitochondria correlate with lower ATP levels and increased generation of nitric oxide, protein nitration, and lipid peroxidation. Moreover, mitochondria–smooth endoplasmic reticulum interactions are compromised due to decreased associations and decreased levels of calnexin and calreticulin, suggesting a disruption in Ca2+ homeostasis and defective unfolded protein responses in aging axons. Despite these age-related modifications, axon function is sustained in aging WM, which suggests that age-dependent changes do not lead to irreversible functional decline under normal conditions, as is observed in neurodegenerative diseases. SIGNIFICANCE STATEMENT Aging is a common risk factor for a number of neurodegenerative diseases, including stroke. Mitochondrial dysfunction and oxidative damage with age are hypothesized to increase risk for stroke. We compared axon–myelin–node–mitochondrion–smooth endoplasmic reticulum (SER) interactions in white matter obtained at 1 and 12 months. We show that aging axons have enlarged volume, thicker myelin, and elongated and thicker mitochondria. Furthermore, there are reduced SER connections to mitochondria that correlate with lower calnexin and calreticulin levels. Despite a prominent decrease in number, elongated aging mitochondria produce excessive stress markers with reduced ATP production. Because axons maintain function under these conditions, our study suggests that it is important to understand the process of normal brain aging to identify neurodegenerative changes. PMID:27683897

Cardioprotection Resulting from Glucagon-Like Peptide-1 Administration Involves Shifting Metabolic Substrate Utilization to Increase Energy Efficiency in the Rat Heart.

PubMed

Aravindhan, Karpagam; Bao, Weike; Harpel, Mark R; Willette, Robert N; Lepore, John J; Jucker, Beat M

2015-01-01

Previous studies have shown that glucagon-like peptide-1 (GLP-1) provides cardiovascular benefits independent of its role on peripheral glycemic control. However, the precise mechanism(s) by which GLP-1 treatment renders cardioprotection during myocardial ischemia remain unresolved. Here we examined the role for GLP-1 treatment on glucose and fatty acid metabolism in normal and ischemic rat hearts following a 30 min ischemia and 24 h reperfusion injury, and in isolated cardiomyocytes (CM). Relative carbohydrate and fat oxidation levels were measured in both normal and ischemic hearts using a 1-13C glucose clamp coupled with NMR-based isotopomer analysis, as well as in adult rat CMs by monitoring pH and O2 consumption in the presence of glucose or palmitate. In normal heart, GLP-1 increased glucose uptake (↑64%, p<0.05) without affecting glycogen levels. In ischemic hearts, GLP-1 induced metabolic substrate switching by increasing the ratio of carbohydrate versus fat oxidation (↑14%, p<0.01) in the LV area not at risk, without affecting cAMP levels. Interestingly, no substrate switching occurred in the LV area at risk, despite an increase in cAMP (↑106%, p<0.05) and lactate (↑121%, p<0.01) levels. Furthermore, in isolated CMs GLP-1 treatment increased glucose utilization (↑14%, p<0.05) and decreased fatty acid oxidation (↓15%, p<0.05) consistent with in vivo finding. Our results show that this benefit may derive from distinct and complementary roles of GLP-1 treatment on metabolism in myocardial sub-regions in response to this injury. In particular, a switch to anaerobic glycolysis in the ischemic area provides a compensatory substrate switch to overcome the energetic deficit in this region in the face of reduced tissue oxygenation, whereas a switch to more energetically favorable carbohydrate oxidation in more highly oxygenated remote regions supports maintaining cardiac contractility in a complementary manner.

A roadmap for the integration of culture into developmental psychopathology.

PubMed

Causadias, José M

2013-11-01

In this paper, I propose a roadmap for the integration of culture in developmental psychopathology. This integration is pressing because culture continues to be somewhat disconnected from theory, research, training, and interventions in developmental psychopathology, thus limiting our understanding of the epigenesis of mental health. I argue that in order to successfully integrate culture into developmental psychopathology, it is crucial to (a) study cultural development, (b) consider both individual-level and social-level cultural processes, (c) examine the interplay between culture and biology, and (d) promote improved and direct cultural assessment. I provide evidence in support of each of these guidelines, present alternative conceptual frameworks, and suggest new lines of research. Hopefully, that these directions will contribute to the emerging field of cultural development and psychopathology, which focuses on the elucidation of the cultural processes that initiate, maintain, or derail trajectories of normal and abnormal behavior.

Fully Convolutional Architecture for Low-Dose CT Image Noise Reduction

NASA Astrophysics Data System (ADS)

Badretale, S.; Shaker, F.; Babyn, P.; Alirezaie, J.

2017-10-01

One of the critical topics in medical low-dose Computed Tomography (CT) imaging is how best to maintain image quality. As the quality of images decreases with lowering the X-ray radiation dose, improving image quality is extremely important and challenging. We have proposed a novel approach to denoise low-dose CT images. Our algorithm learns directly from an end-to-end mapping from the low-dose Computed Tomography images for denoising the normal-dose CT images. Our method is based on a deep convolutional neural network with rectified linear units. By learning various low-level to high-level features from a low-dose image the proposed algorithm is capable of creating a high-quality denoised image. We demonstrate the superiority of our technique by comparing the results with two other state-of-the-art methods in terms of the peak signal to noise ratio, root mean square error, and a structural similarity index.

Construction of special eye models for investigation of chromatic and higher-order aberrations of eyes.

PubMed

Zhai, Yi; Wang, Yan; Wang, Zhaoqi; Liu, Yongji; Zhang, Lin; He, Yuanqing; Chang, Shengjiang

2014-01-01

An achromatic element eliminating only longitudinal chromatic aberration (LCA) while maintaining transverse chromatic aberration (TCA) is established for the eye model, which involves the angle formed by the visual and optical axis. To investigate the impacts of higher-order aberrations on vision, the actual data of higher-order aberrations of human eyes with three typical levels are introduced into the eye model along visual axis. Moreover, three kinds of individual eye models are established to investigate the impacts of higher-order aberrations, chromatic aberration (LCA+TCA), LCA and TCA on vision under the photopic condition, respectively. Results show that for most human eyes, the impact of chromatic aberration on vision is much stronger than that of higher-order aberrations, and the impact of LCA in chromatic aberration dominates. The impact of TCA is approximately equal to that of normal level higher-order aberrations and it can be ignored when LCA exists.

Ultra-structural study of insulin granules in pancreatic β-cells of db/db mouse by scanning transmission electron microscopy tomography.

PubMed

Xue, Yanhong; Zhao, Wei; Du, Wen; Zhang, Xiang; Ji, Gang; Ying, Wang; Xu, Tao

2012-07-01

Insulin granule trafficking is a key step in the secretion of glucose-stimulated insulin from pancreatic β-cells. The main feature of type 2 diabetes (T2D) is the failure of pancreatic β-cells to secrete sufficient amounts of insulin to maintain normal blood glucose levels. In this work, we developed and applied tomography based on scanning transmission electron microscopy (STEM) to image intact insulin granules in the β-cells of mouse pancreatic islets. Using three-dimensional (3D) reconstruction, we found decreases in both the number and the grey level of insulin granules in db/db mouse pancreatic β-cells. Moreover, insulin granules were closer to the plasma membrane in diabetic β-cells than in control cells. Thus, 3D ultra-structural tomography may provide new insights into the pathology of insulin secretion in T2D.

Photovoltaic array: Power conditioner interface characteristics

NASA Technical Reports Server (NTRS)

Gonzalez, C. C.; Hill, G. M.; Ross, R. G., Jr.

1982-01-01

The electrical output (power, current, and voltage) of flat plate solar arrays changes constantly, due primarily to changes in cell temperature and irradiance level. As a result, array loads such as dc-to-ac power conditioners must be capable of accommodating widely varying input levels while maintaining operation at or near the maximum power point of the array. The array operating characteristics and extreme output limits necessary for the systematic design of array load interfaces under a wide variety of climatic conditions are studied. A number of interface parameters are examined, including optimum operating voltage, voltage energy, maximum power and current limits, and maximum open circuit voltage. The effect of array degradation and I-V curve fill factor or the array power conditioner interface is also discussed. Results are presented as normalized ratios of power conditioner parameters to array parameters, making the results universally applicable to a wide variety of system sizes, sites, and operating modes.

Assessment of parental awareness about malocclusion in Shiraz, Islamic Republic of Iran.

PubMed

Danaei, S Momeni; Oshagh, M; Pajuhi, N; Ghahremani, Y; Bushehri, Ghodsi S

2011-07-01

Information empowers people to take charge of their health. The aim of this study in Shiraz, Islamic Republic of Iran was to evaluate parents' knowledge about dental malocclusion, referral routes and information sources. A random sample of 1000 7-9-year-old schoolchildren were given a questionnaire to complete at home. Questionnaires were completed by 795 parents. Knowledge about malocclusion was significantly greater in families with higher levels of education and income. Most respondents (83.5%) were aware of the importance of maintaining primary teeth to prevent malocclusion, and 25.1% thought that carious primary teeth must be extracted. Half of the parents (50.6%) did not know that spaces between primary teeth are normal. Only 28.8% of the children visited dentists for annual routine check-ups. Television (43.3%) was the most common source of dental information. The level of general public awareness about malocclusion needs to be improved.

Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat.

PubMed

Michalkiewicz, Mieczyslaw; Michalkiewicz, Teresa; Ettinger, Ruth A; Rutledge, Elizabeth A; Fuller, Jessica M; Moralejo, Daniel H; Van Yserloo, Brian; MacMurray, Armand J; Kwitek, Anne E; Jacob, Howard J; Lander, Eric S; Lernmark, Ake

2004-10-04

A single point mutation in a novel immune-associated nucleotide gene 5 (Ian5) coincides with severe T cell lymphopenia in BB rats. We used a transgenic rescue approach in lymphopenic BB-derived congenic F344.lyp/lyp rats to determine whether this mutation is responsible for lymphopenia and to establish the functional importance of this novel gene. A 150-kb P1 artificial chromosome (PAC) transgene harboring a wild-type allele of the rat Ian5 gene restored Ian5 transcript and protein levels, completely rescuing the T cell lymphopenia in the F344.lyp/lyp rats. This successful complementation provides direct functional evidence that the Ian5 gene product is essential for maintaining normal T cell levels. It also demonstrates that transgenic rescue in the rat is a practical and definitive method for revealing the function of a novel gene.

Effects of body temperature on post-anoxic oxidative stress from the perspective of postnatal physiological adaptive processes in rats.

PubMed

Kletkiewicz, H; Rogalska, J; Nowakowska, A; Wozniak, A; Mila-Kierzenkowska, C; Caputa, M

2016-04-01

It is well known that decrease in body temperature provides protection to newborns subjected to anoxia/ischemia. We hypothesized that the normal body temperature of 33°C in neonatal rats (4°C below normal body temperature in adults) is in fact a preadaptation to protect CNS from anoxia and further reductions as well as elevations in temperature may be counterproductive. Our experiments aimed to examine the effect of changes in body temperature on oxidative stress development in newborn rats exposed to anoxia. Two-day-old Wistar rats were divided into 4 temperature groups: i. hypothermic at body temperature of 31°C, ii. maintaining physiological neonatal body temperature of 33°C, iii. forced to maintain hyperthermic temperature of 37°C, and i.v. forced to maintain hyperthermic temperature of 39°C. The temperature was controlled starting 15 minutes before and afterword during 10 minutes of anoxia as well as for 2 hours post-anoxia. Cerebral concentrations of lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) and the activities of antioxidant enzymes had been determined post mortem: immediately after anoxia was finished and 3, 7, and 14 days later. There were no post-anoxic changes in the concentration of MDA, CD and in antioxidant enzymes activity in newborn rats kept at their physiological body temperature of 33°C. In contrast, perinatal anoxia at body temperature elevated to 37°C or 39°C as well as under hypothermic conditions (31°C) intensified post-anoxic oxidative stress and depleted the antioxidant pool. Overall, these findings suggest that elevated body temperature (hyperthermia or fever), as well as exceeding cooling beyond the physiological level of body temperature of newborn rats, may extend perinatal anoxia-induced brain lesions. Our findings provide new insights into the role of body temperature in anoxic insult in vivo.

Lentiviral-mediated gene therapy results in sustained expression of β-glucuronidase for up to 12 months in the gus(mps/mps) and up to 18 months in the gus(tm(L175F)Sly) mouse models of mucopolysaccharidosis type VII.

PubMed

Derrick-Roberts, Ainslie L K; Pyragius, Carmen E; Kaidonis, Xenia M; Jackson, Matilda R; Anson, Donald S; Byers, Sharon

2014-09-01

A number of mucopolysaccharidosis type VII (MPS VII) mouse models with different levels of residual enzyme activity have been created replicating the range of clinical phenotypes observed in human MPS VII patients. In this study, a lentivirus encoding murine β-glucuronidase was administered intravenously at birth to both the severe (Gus(mps/mps) strain) and attenuated (Gus(tm(L175F)Sly) strain) mouse models of MPS VII. Circulating enzyme levels were normalized in the Gus(mps/mps) mice and were 3.5-fold higher than normal in the Gus(tm(L175F)Sly) mouse 12 and 18 months after administration. Tissue β-glucuronidase activity increased over untreated levels in all tissues evaluated in both strains at 12 months, and the elevated level was maintained in Gus(tm(L175F)Sly) tissues at 18 months. These elevated enzyme levels reduced glycosaminoglycan storage in the liver, spleen, kidney, and heart in both models. Bone mineral volume decreased toward normal in both models after 12 months of therapy and after 18 months in the Gus(tm(L175F)Sly) mouse. Open-field exploration was improved in 18-month-old treated Gus(tm(L175F)Sly) mice, while spatial learning improved in both 12- and 18-month-old treated Gus(tm(L175F)Sly) mice. Overall, neonatal administration of lentiviral gene therapy resulted in sustained enzyme expression for up to 18 months in murine models of MPS VII. Significant improvements in biochemistry and enzymology as well as functional improvement of bone and behavior deficits in the Gus(tm(L175F)Sly) model were observed. Therapy significantly increased the lifespan of Gus(mps/mps) mice, with 12 months being the longest reported lentiviral treatment for this strain. It is important to assess the long-term outcome on enzyme levels and effect on pathology for lentiviral gene therapy to be a potential therapy for MPS patients.

78 FR 22870 - Free Flow Power Corporation; Notice of Application Accepted for Filing and Soliciting Motions To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-17

... Natural Resources and impounds a 553-acre reservoir at a normal pool elevation of 472.2 North American... the existing Williams dam owned by the Indiana Department of Natural Resources on the East Fork White... maintained at the existing normal pool elevation (crest of the dam spillway) or above. The average annual...

Deletions of VCX-A and NLGN4: A Variable Phenotype Including Normal Intellect

ERIC Educational Resources Information Center

Macarov, M.; Zeigler, M.; Newman, J. P.; Strich, D.; Sury, V.; Tennenbaum, A.; Meiner, V.

2007-01-01

Background: Patients with Xp22.3 interstitial and terminal deletions have been shown to be affected by intellectual disability (ID) or autism. Previously, "VCX-A" (variably charged protein X-A), located at Xp22.3, was introduced as a gene for ID and its presence was suggested to be sufficient to maintain normal mental development. Recent reports…

47 CFR 80.305 - Watch requirements of the Communications Act and the Safety Convention.

Code of Federal Regulations, 2012 CFR

2012-10-01

... vessel is normally steered while being navigated in the open sea outside a harbor or port. (2) Keep a...-DSC radio equipment, must, while being navigated in the open sea or any tidewater within the... is normally steered while in the open sea outside a harbor or port. The watch must be maintained by a...

47 CFR 80.305 - Watch requirements of the Communications Act and the Safety Convention.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vessel is normally steered while being navigated in the open sea outside a harbor or port. (2) Keep a...-DSC radio equipment, must, while being navigated in the open sea or any tidewater within the... is normally steered while in the open sea outside a harbor or port. The watch must be maintained by a...

47 CFR 80.305 - Watch requirements of the Communications Act and the Safety Convention.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vessel is normally steered while being navigated in the open sea outside a harbor or port. (2) Keep a...-DSC radio equipment, must, while being navigated in the open sea or any tidewater within the... is normally steered while in the open sea outside a harbor or port. The watch must be maintained by a...

Deciphering the potential efficacy of acetyl-L-carnitine (ALCAR) in maintaining connexin-mediated lenticular homeostasis

PubMed Central

Muralidharan, Arumugam Ramachandran; Leema, George; Annadurai, Thangaraj; Anitha, Thirugnanasambandhar Sivasubramanian; Thomas, Philip A.

2012-01-01

Purpose To determine the putative role of acetyl-L-carnitine (ALCAR) in maintaining normal intercellular communication in the lens through connexin. Methods In the present study, Wistar rat pups were divided into 3 groups of eight each. On postpartum day ten, Group I rat pups received an intraperitoneal injection (50 µl) of 0.89% saline. Rats in Groups II and III received a subcutaneous injection (50 µl) of sodium selenite (19 µmol/kg bodyweight); Group III rat pups also received an intraperitoneal injection of ALCAR (200 mg/kg bodyweight) once daily on postpartum days 9–14. Both eyes of each pup were examined from day 16 up to postpartum day 30. Alterations in the mean activity of the channel pumps, calcium-ATPase and sodium/potassium-ATPase, were determined. The expression of genes encoding key lenticular gap junctions (connexin 46 and connexin 50) and a channel pump (plasma membrane Ca2+-ATPase [PMCA1]) was evaluated by reverse transcription-PCR. Immunoblot analysis was also performed to confirm the differential expression of key lenticular connexin proteins. In addition, bioinformatics analysis was performed to determine the interacting residues of the connexin proteins with ALCAR. Results Significantly lower mean activities of Ca2+-ATPase and Na+/K+ -ATPase were observed in the lenses of Group II rats than those in Group I rat lenses. However, the observed mean activities of Ca2+-ATPase and Na+/K+-ATPase in Group III rat lenses were significantly higher than those in Group II rat lenses. The mean mRNA transcript levels of the connexin 46 and connexin 50 genes were significantly lower, while the mean levels of PMCA1 gene transcripts were significantly higher, in Group II rat lenses than in Group I rat lenses. Immunoblot analysis also confirmed the altered expression of connexin proteins in lysates of whole lenses of Group II rats. However, the expression of connexin 46 and connexin 50 proteins in lenses from group III rats was essentially similar to that noted in lenses from normal (Group I) rats. Hydrogen bond-interaction between ALCAR and amino acid residues at the functional domain regions of connexin 46 and connexin 50 proteins was also demonstrated through bioinformatics tools. Conclusions The results suggest that ALCAR plays a key role in maintaining lenticular homeostasis by promoting gap junctional intercellular communication. PMID:22876134

Deciphering the potential efficacy of acetyl-L-carnitine (ALCAR) in maintaining connexin-mediated lenticular homeostasis.

PubMed

Muralidharan, Arumugam Ramachandran; Leema, George; Annadurai, Thangaraj; Anitha, Thirugnanasambandhar Sivasubramanian; Thomas, Philip A; Geraldine, Pitchairaj

2012-01-01

To determine the putative role of acetyl-L-carnitine (ALCAR) in maintaining normal intercellular communication in the lens through connexin. In the present study, Wistar rat pups were divided into 3 groups of eight each. On postpartum day ten, Group I rat pups received an intraperitoneal injection (50 µl) of 0.89% saline. Rats in Groups II and III received a subcutaneous injection (50 µl) of sodium selenite (19 µmol/kg bodyweight); Group III rat pups also received an intraperitoneal injection of ALCAR (200 mg/kg bodyweight) once daily on postpartum days 9-14. Both eyes of each pup were examined from day 16 up to postpartum day 30. Alterations in the mean activity of the channel pumps, calcium-ATPase and sodium/potassium-ATPase, were determined. The expression of genes encoding key lenticular gap junctions (connexin 46 and connexin 50) and a channel pump (plasma membrane Ca(2+)-ATPase [PMCA1]) was evaluated by reverse transcription-PCR. Immunoblot analysis was also performed to confirm the differential expression of key lenticular connexin proteins. In addition, bioinformatics analysis was performed to determine the interacting residues of the connexin proteins with ALCAR. Significantly lower mean activities of Ca(2+)-ATPase and Na(+)/K(+) -ATPase were observed in the lenses of Group II rats than those in Group I rat lenses. However, the observed mean activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase in Group III rat lenses were significantly higher than those in Group II rat lenses. The mean mRNA transcript levels of the connexin 46 and connexin 50 genes were significantly lower, while the mean levels of PMCA1 gene transcripts were significantly higher, in Group II rat lenses than in Group I rat lenses. Immunoblot analysis also confirmed the altered expression of connexin proteins in lysates of whole lenses of Group II rats. However, the expression of connexin 46 and connexin 50 proteins in lenses from group III rats was essentially similar to that noted in lenses from normal (Group I) rats. Hydrogen bond-interaction between ALCAR and amino acid residues at the functional domain regions of connexin 46 and connexin 50 proteins was also demonstrated through bioinformatics tools. The results suggest that ALCAR plays a key role in maintaining lenticular homeostasis by promoting gap junctional intercellular communication.

Delayed degradation of chlorophylls and photosynthetic proteins in Arabidopsis autophagy mutants during stress-induced leaf yellowing

PubMed Central

Sakuraba, Yasuhito; Lee, Sang-Hwa; Kim, Ye-Sol; Park, Ohkmae K.; Hörtensteiner, Stefan; Paek, Nam-Chon

2014-01-01

Plant autophagy, one of the essential proteolysis systems, balances proteome and nutrient levels in cells of the whole plant. Autophagy has been studied by analysing Arabidopsis thaliana autophagy-defective atg mutants, but the relationship between autophagy and chlorophyll (Chl) breakdown during stress-induced leaf yellowing remains unclear. During natural senescence or under abiotic-stress conditions, extensive cell death and early yellowing occurs in the leaves of atg mutants. A new finding is revealed that atg5 and atg7 mutants exhibit a functional stay-green phenotype under mild abiotic-stress conditions, but leaf yellowing proceeds normally in wild-type leaves under these conditions. Under mild salt stress, atg5 leaves retained high levels of Chls and all photosystem proteins and maintained a normal chloroplast structure. Furthermore, a double mutant of atg5 and non-functional stay-green nonyellowing1-1 (atg5 nye1-1) showed a much stronger stay-green phenotype than either single mutant. Taking these results together, it is proposed that autophagy functions in the non-selective catabolism of Chls and photosynthetic proteins during stress-induced leaf yellowing, in addition to the selective degradation of Chl–apoprotein complexes in the chloroplasts through the senescence-induced STAY-GREEN1/NYE1 and Chl catabolic enzymes. PMID:24510943

BIG: a calossin-like protein required for polar auxin transport in Arabidopsis

PubMed Central

Gil, Pedro; Dewey, Elizabeth; Friml, Jiri; Zhao, Yunde; Snowden, Kimberley C.; Putterill, Jo; Palme, Klaus; Estelle, Mark; Chory, Joanne

2001-01-01

Polar auxin transport is crucial for the regulation of auxin action and required for some light-regulated responses during plant development. We have found that two mutants of Arabidopsis—doc1, which displays altered expression of light-regulated genes, and tir3, known for its reduced auxin transport—have similar defects and define mutations in a single gene that we have renamed BIG. BIG is very similar to the Drosophila gene Calossin/Pushover, a member of a gene family also present in Caenorhabditis elegans and human genomes. The protein encoded by BIG is extraordinary in size, 560 kD, and contains several putative Zn-finger domains. Expression-profiling experiments indicate that altered expression of multiple light-regulated genes in doc1 mutants can be suppressed by elevated levels of auxin caused by overexpression of an auxin biosynthetic gene, suggesting that normal auxin distribution is required to maintain low-level expression of these genes in the dark. Double mutants of tir3 with the auxin mutants pin1, pid, and axr1 display severe defects in auxin-dependent growth of the inflorescence. Chemical inhibitors of auxin transport change the intracellular localization of the auxin efflux carrier PIN1 in doc1/tir3 mutants, supporting the idea that BIG is required for normal auxin efflux. PMID:11485992

Development of the normal gastrointestinal microflora of specific pathogen-free chickens.

PubMed

Coloe, P J; Bagust, T J; Ireland, L

1984-02-01

The development of the normal intestinal microflora of the small intestine, caecum and large intestine of specific pathogen-free (SPF) chickens, was studied in the period from hatching to 84 days of age. No bacteria were detected in any of the sites at hatchery (day 1), but by day 3 significant levels of faecal streptococci and coliforms were isolated from all sites. The flora of the small intestine was limited to faecal streptococci and coliforms for the first 40 days and then lactobacilli became established and dominated the flora. A large variety of facultative and strictly anaerobic organisms colonized the caecum. Many of these species were transient and were only present for a limited period; after 40 days the flora stabilized to consist predominantly of faecal streptococci, Escherichia coli, Bacteroides spp. and Lactobacillus sp. The flora of the large intestine was composed of organisms also present in the small intestine or the caecum. These findings differ from previously published studies on conventionally reared chickens in that the number of species isolated and the population levels of organisms are much lower. This probably reflects the absence of continuous environmental challenge to the chickens because of the housing and feeding facilities in which the chickens were maintained.

Thermal anomalies of the transmitter experiment package on the communications technology satellite

NASA Technical Reports Server (NTRS)

Alexovich, R. E.; Curren, A. N.

1979-01-01

The causes of four temporary thermal-control-system malfunctions that gave rise to unexpected temperature excursions in the 12-gigahertz, 200-watt transmitter experiment package (TEP) on the Communications Technology Satellite were investigated. The TEP consists of a nominal 200-watt output stage tube (OST), a supporting power-processing system (PPS), and a variable-conductance heat-pipe system (VCHPS). The VCHPS, which uses three heat pipes to conduct heat from the body of the OST to a radiator fin, was designed to maintain the TEP at safe operating temperatures at all operating conditions. On four occasions during 1977, all near the spring and fall equinoxes, the OST body temperature and related temperatures displayed sudden, rapid, and unexpected rises above normal levels while the TEP was operating at essentially constant, normal conditions. The temperature excursions were terminated without TEP damage by reducing the radio frequency (RF) output power of the OST. Between the anomalies and since the fourth, the thermal control system has apparently functioned as designed. The results indicate the most probable cause of the temperature anomalies is depriming of the arteries in the variable-conductance heat pipes. A mode was identified in which the TEP, as presently configured, may operate with stable temperatures and with minimum change in performance level.

The MADS transcription factor XAL2/AGL14 modulates auxin transport during Arabidopsis root development by regulating PIN expression

PubMed Central

Garay-Arroyo, Adriana; Ortiz-Moreno, Enrique; de la Paz Sánchez, María; Murphy, Angus S; García-Ponce, Berenice; Marsch-Martínez, Nayelli; de Folter, Stefan; Corvera-Poiré, Adriana; Jaimes-Miranda, Fabiola; Pacheco-Escobedo, Mario A; Dubrovsky, Joseph G; Pelaz, Soraya; Álvarez-Buylla, Elena R

2013-01-01

Elucidating molecular links between cell-fate regulatory networks and dynamic patterning modules is a key for understanding development. Auxin is important for plant patterning, particularly in roots, where it establishes positional information for cell-fate decisions. PIN genes encode plasma membrane proteins that serve as auxin efflux transporters; mutations in members of this gene family exhibit smaller roots with altered root meristems and stem-cell patterning. Direct regulators of PIN transcription have remained elusive. Here, we establish that a MADS-box gene (XAANTAL2, XAL2/AGL14) controls auxin transport via PIN transcriptional regulation during Arabidopsis root development; mutations in this gene exhibit altered stem-cell patterning, root meristem size, and root growth. XAL2 is necessary for normal shootward and rootward auxin transport, as well as for maintaining normal auxin distribution within the root. Furthermore, this MADS-domain transcription factor upregulates PIN1 and PIN4 by direct binding to regulatory regions and it is required for PIN4-dependent auxin response. In turn, XAL2 expression is regulated by auxin levels thus establishing a positive feedback loop between auxin levels and PIN regulation that is likely to be important for robust root patterning. PMID:24121311

PHYSIOLOGICAL EFFECTS OF DEUTERIUM ON DOGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czajka, D.M.; Finkel, A.J.; Fischer, C.S.

1961-08-01

The physiological consequences of the deuterium isotope effect in lange mammals were studied in two dogs, one of which was maintained at 20% concentration of D/sub 2/0 in the bcdy fluids for 50 days, and the other at the toxic range of 33-35% for a brief pericd. Deuteration of the dcgs was effected by replacement of ordinary water with deuterium oxide in both focd and drink. Hemoglobin, hematocrit, and red blood cell count dropped but the white blood cell count was essentially unaffected although there was a progressive lymphopenia and granulocytosis. Serum glucose was decreased, especially at higher deuterium levels.more » Total serum cholesterol values were also diminished although the esters were essentially unchanged. Serum sodium and both NPN and BUN were within normal limits except for a terminal elevation of the latter. Serum potassium was slightly lowered for a brief period after 3 weeks. Electrocardiograms showed ST segment coving and elevation and an increase in the QT ratio that suggested nonspecific myocardial damage; these changes reverted to normal while the dog was still deuterated at a level of 20%. Both dogs exhibited neuromuscular disturbances, in one case definite weakness of the hind legs and in the other, fine muscle tremors. (auth)« less

[Expression of FAP and alpha-SMA during the incised wound healing in mice skin].

PubMed

Gao, Yang; Peng, Xue; Jin, Zhan-Fen; Fu, Zhi-Jun

2009-12-01

OBJECTIVE To investigate the time-dependent expression of fibroblast activation protein (FAP) and alpha-smooth muscle actin(alpha-SMA) during the incised wound healing of the skin in mice. The expression of FAP and alpha-SMA in incised wound of mice skin was detected by immunohistochemistry and Western blot. By immunohistochemistry, the expression of FAP and alpha-SMA in the normal skin and the skin 1 h after injury maintained at a very low level, but the positive cells expressing FAP and alpha-SMA started to elevate 6 h after injury and reached its peak on 5 d for FAP and on 3 d for alpha-SMA, then gradually decreased to the normal level on 14 d. The expression of FAP and alpha-SMA was observed throughout the wound healing stages 1 d after injuries by Western blot as well with a peak expression occurring on 5 d for FAP and on 3 d for alpha-SMA after injury. FAP may be a potentially useful marker for wound age determination and alpha-SMA may be used as an effective indicator for the mid- and late stage incised wound of mice skin. The combination use of FAP and alpha-SMA may be potentially effective indicators for wound age determination.

Tachycardia, reduced vagal capacity, and age-dependent ventricular dysfunction arising from diminished expression of the presynaptic choline transporter.

PubMed

English, Brett A; Appalsamy, Martin; Diedrich, Andre; Ruggiero, Alicia M; Lund, David; Wright, Jane; Keller, Nancy R; Louderback, Katherine M; Robertson, David; Blakely, Randy D

2010-09-01

Healthy cardiovascular function relies on a balanced and responsive integration of noradrenergic and cholinergic innervation of the heart. High-affinity choline uptake by cholinergic terminals is pivotal for efficient ACh production and release. To date, the cardiovascular impact of diminished choline transporter (CHT) expression has not been directly examined, largely due to the transporter's inaccessibility in vivo. Here, we describe findings from cardiovascular experiments using transgenic mice that bear a CHT genetic deficiency. Whereas CHT knockout (CHT(-/-)) mice exhibit early postnatal lethality, CHT heterozygous (CHT(+/-)) mice survive, grow, and reproduce normally and exhibit normal spontaneous behaviors. However, the CHT(+/-) mouse heart displays significantly reduced levels of high-affinity choline uptake accompanied by significantly reduced levels of ACh. Telemeterized recordings of cardiovascular function in these mice revealed tachycardia and hypertension at rest. After treadmill exercise, CHT(+/-) mice exhibited slower heart rate recovery, consistent with a diminished cholinergic reserve, a contention validated through direct vagal nerve stimulation. Echocardiographic and histological experiments revealed an age-dependent decrease in fractional shortening, increased left ventricular dimensions, and increased ventricular fibrosis, consistent with ventricular dysfunction. These cardiovascular phenotypes of CHT(+/-) mice encourage an evaluation of humans bearing reduced CHT expression for their resiliency in maintaining proper heart function as well as risk for cardiovascular disease.

Neurological complications of lumbar artificial disc replacement and comparison of clinical results with those related to lumbar arthrodesis in the literature: results of a multicenter, prospective, randomized investigational device exemption study of Charité intervertebral disc. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.

PubMed

Geisler, Fred H; Blumenthal, Scott L; Guyer, Richard D; McAfee, Paul C; Regan, John J; Johnson, J Patrick; Mullin, Bradford

2004-09-01

Arthrodesis is the gold standard for surgical treatment of lumbar degenerative disc disease (DDD). Solid fusion, however, can cause stress and increased motion in the segments adjacent to the fused level. This may initiate and/or accelerate the adjacent-segment disease process. Artificial discs are designed to restore and maintain normal motion of the lumbar intervertebral segment. Restoring and maintaining normal motion of the segment reduces stresses and loads on adjacent level segments. A US Food and Drug Administration Investigational Device Exemptions multicentered study of the Charité artificial disc was completed. The control group consisted of individuals who underwent anterior lumbar interbody fusion involving BAK cages and iliac crest bone graft. This is the first report of Class I data in which a lumbar artificial disc is compared with lumbar fusion. Of 304 individuals enrolled in the study, 205 were randomized to the Charité disc-treated group and 99 to the BAK fusion-treated (control) group. Neurological status was equivalent between the two groups at 6, 12, and 24 months postoperatively. The number of patients with major, minor, or other neurological complications was equivalent. There was a greater incidence of both major and minor complications in the BAK fusion group at 0 to 42 days postoperatively. Compared with data reported in the lumbar fusion literature, the Charité disc-treated patients had equivalent or better mean changes in visual analog scale and Oswestry Disability Index scores. The Charité artificial disc is safe and effective for the treatment of single-level lumbar DDD, resulting in no higher incidence of neurological complications compared with BAK-assisted fusion and leading to equivalent or better outcomes compared with those obtained in the control group and those reported in the lumbar fusion literature.

Has enhanced folate status during pregnancy altered natural selection and possibly Autism prevalence? A closer look at a possible link.

PubMed

Rogers, Eugene J

2008-09-01

The inverse association between maternal folate status and incidence of infants born with neural tube defects (NTD's) was recognized over twenty years ago and led the US health agencies in the early 1990s to recommend that women of childbearing age consume 400 microg of folic acid each day. The FDA followed by mandating that certain foods be fortified with folic acid and this has resulted in a significant enhancement of maternal folate status to levels that are often difficult to otherwise achieve naturally. At least one study indicates that this has decreased the incidence of NTD's. However, this same time period directly coincides with what many feel is the apparent beginning and continuous increase in the prevalence of Autism and related Autism Spectrum Disorders (ASD's) in the US. Are these similar time frames of changes in maternal folate status and possible Autism prevalence a random event or has improved maternal (and fetal) folate status during pregnancy played a role? It is not only plausible but highly likely. A particular polymorphic form to a key enzyme required to activate folate for methylation in neurodevelopment, 5-methylenetetrahydrofolate reductase (MTHFR), demonstrates reduced activity under low or normal folate levels but normal activity under conditions of higher folate nutritional status. A consequence of the presence of the polymorphic form of this enzyme during normal or reduced folate status are higher plasma homocysteine levels than noncarriers and the combination of these factors have been shown in several studies to result in an increase rate of miscarriage via thrombotic events. However, the incidence of hyperhomocysteinemia in the presence of the polymorphism is reduced under the common condition of enhanced folate status and thereby masks the latent adverse effects of the presence of this enzyme form during pregnancy. Of great importance is that this polymorphism, although common in the normal population, is found in significantly higher frequency in Autisic individuals. It is hypothesized here that the enhancement of maternal folate status before and during pregnancy in the last 15 years has altered natural selection by increasing survival rates during pregnancy of infants possessing the MTHFR C677T polymorphism, via reduction in hyperhomocysteinemia associated with this genotype and thereby miscarriage rates. This also points directly to an increased rate of births of infants with higher postnatal requirements for folic acid needed for normal methylation during this critical neurodevelopmental period. If these numbers have increased then so have the absolute number of infants that after birth fail to maintain the higher folate status experienced in utero thus leading to an increased number of cases of developmental disorders such as Autism. Detection of the C677T polymorphism as well as other methionine cycle enzymes related to folate metabolism and methylation at birth as part of newborn screening programs could determine which newborns need be monitored and maintained on diets or supplements that ensure adequate folate status during this critical postnatal neurodevelopment period.

Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity

PubMed Central

Im, Michelle; Dagnino, Lina

2018-01-01

The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity. PMID:29568383

Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity.

PubMed

Im, Michelle; Dagnino, Lina

2018-03-02

The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity.

Signals for glucagon secretion.

PubMed

Bloom, S R

1977-01-01

The normal physiological role of glucagon is in controlling hepatic glucose output. Glucagon subserves the role of homeostasis by maintaining plasma glucose and of a stress hormone by producing hyperglycaemia. While control of glucagon release by circulating metabolites and also other hormones is clearly important, it seems likely that the nervous system exerts an over-riding influence. The parasympathetic nervous system maintains homeostasis and the sympathetic acts in stress. Glucagon levels are found to be high in cirrhosis and also after acute hepatic failure. It is likely that these changes in glucagon concentration are secondary to metabolic abnormalities. While some glucagon is cleared by the liver, a similar clearance is seen by many other tissues and it is not likely that the elevation of glucagon seen in liver failure is due solely to a gross deficiency of glucagon clearance. No liver abnormality is seen in the glucagonoma syndrome, where glucagon concentration are chronically high, or in patients who have had a total pancreatectomy, where plasma glucagon is undetectably low. It thus seems unlikely that liver mass is importantly controlled by glucagon.

An improved parent-centric mutation with normalized neighborhoods for inducing niching behavior in differential evolution.

PubMed

Biswas, Subhodip; Kundu, Souvik; Das, Swagatam

2014-10-01

In real life, we often need to find multiple optimally sustainable solutions of an optimization problem. Evolutionary multimodal optimization algorithms can be very helpful in such cases. They detect and maintain multiple optimal solutions during the run by incorporating specialized niching operations in their actual framework. Differential evolution (DE) is a powerful evolutionary algorithm (EA) well-known for its ability and efficiency as a single peak global optimizer for continuous spaces. This article suggests a niching scheme integrated with DE for achieving a stable and efficient niching behavior by combining the newly proposed parent-centric mutation operator with synchronous crowding replacement rule. The proposed approach is designed by considering the difficulties associated with the problem dependent niching parameters (like niche radius) and does not make use of such control parameter. The mutation operator helps to maintain the population diversity at an optimum level by using well-defined local neighborhoods. Based on a comparative study involving 13 well-known state-of-the-art niching EAs tested on an extensive collection of benchmarks, we observe a consistent statistical superiority enjoyed by our proposed niching algorithm.

Exercise as a countermeasure for physiological adaptation to prolonged spaceflight

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1996-01-01

Exercise represents the primary countermeasure used during spaceflight to maintain or restore maximal aerobic capacity (VO2max), musculoskeletal structure, and orthostatic function. However, no single exercise or combination of prescriptions has proven entirely effective in restoring cardiovascular and musculoskeletal functions to preflight levels following prolonged spaceflight. As human spaceflight exposures increase in duration, assessment and development of various effective exercise-based protective procedures become paramount. This must involve improvement in specific countermeasure prescription as well as development of additional approaches that will allow space travelers greater flexibility and medical safety during long flights. Effective exercise prescription will be based on identification of basic physiological stimuli that maintain normal function in terrestrial gravity and understanding of how specific combinations of exercise characteristics e.g., duration, frequency, intensity, mode) can mimic these stimuli and affect the overall process of adaptation to microgravity. This can be accomplished only with greater emphasis of research on ground-based experiments. Future attention must be directed to improving exercise compliance while minimizing both crew time and the impact of the exercise on life-support resources.

Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens

PubMed Central

Nowak, Roberta B.; Fischer, Robert S.; Zoltoski, Rebecca K.; Kuszak, Jerome R.

2009-01-01

Hexagonal packing geometry is a hallmark of close-packed epithelial cells in metazoans. Here, we used fiber cells of the vertebrate eye lens as a model system to determine how the membrane skeleton controls hexagonal packing of post-mitotic cells. The membrane skeleton consists of spectrin tetramers linked to actin filaments (F-actin), which are capped by tropomodulin1 (Tmod1) and stabilized by tropomyosin (TM). In mouse lenses lacking Tmod1, initial fiber cell morphogenesis is normal, but fiber cell hexagonal shapes and packing geometry are not maintained as fiber cells mature. Absence of Tmod1 leads to decreased γTM levels, loss of F-actin from membranes, and disrupted distribution of β2-spectrin along fiber cell membranes. Regular interlocking membrane protrusions on fiber cells are replaced by irregularly spaced and misshapen protrusions. We conclude that Tmod1 and γTM regulation of F-actin stability on fiber cell membranes is critical for the long-range connectivity of the spectrin–actin network, which functions to maintain regular fiber cell hexagonal morphology and packing geometry. PMID:19752024

Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nataf, Robert; Skorupka, Corinne; Amet, Lorene

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001).more » Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.« less

Accelerated relative sea-level rise and rapid coastal erosion: Testing a causal relationship for the Louisiana barrier islands

USGS Publications Warehouse

List, J.H.; Sallenger, A.H.; Hansen, M.E.; Jaffe, B.E.

1997-01-01

The role of relative sea-level rise as a cause for the rapid erosion of Louisiana's barrier island coast is investigated through a numerical implementation of a modified Bruun rule that accounts for the low percentage of sand-sized sediment in the eroding Louisiana shoreface. Shore-normal profiles from 150 km of coastline west of the Mississippi delta are derived from bathymetric surveys conducted during the 1880s. 1930s and 1980s. An RMS difference criterion is employed to test whether an equilibrium profile form is maintained between survey years. Only about half the studied profiles meet the equilibrium Criterion this represents a significant limitation on the potential applicability of the Bruun rule. The profiles meeting the equilibrium criterion, along with measured rates of relative sea-level rise, are used to hindcast shoreline retreat rates at 37 locations within the study area. Modeled and observed shoreline retreat rates show no significant correlation. Thus in terms of the Bruun approach relative sea-level rise has no power for hindcasting (and presumably forecasting) rates of coastal erosion for the Louisiana barrier islands.

Porphyrinuria in childhood autistic disorder: implications for environmental toxicity.

PubMed

Nataf, Robert; Skorupka, Corinne; Amet, Lorene; Lam, Alain; Springbett, Anthea; Lathe, Richard

2006-07-15

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.

Hyperthyroidism-associated hypercalcemic crisis: A case report and review of the literature.

PubMed

Chen, Ke; Xie, Yanhong; Zhao, Liling; Mo, Zhaohui

2017-01-01

Hyperthyroidism is one of the major clinical causes of hypercalcaemia, however, hyperthyroidism-related hypercalcemic crisis is rare, only 1 case have been reported. The potential mechanisms are still not too clear. It may be related that thyroid hormone stimulate bone turnover, elevate serum calcium, increase urinary and fecal calcium excretion. A 58-year-old female patient was found to have Graves' disease, a marked elevated serum calcium level (adjusted serum calcium: 3.74 mmol/L), and reduced parathyroid hormone level. She was diagnosed as hyperthyroidism-associated hypercalcemic crisis. Treatment with methimazole to correct the hyperthyroidism and treatment of the patient's hypercalcaemia was achieved by physiological saline, salmon calcitonin and furosemide. After treatment for hypercalcaemia and hyperthyroidism, her symptoms and serum calcium levels quickly returned to normal. hyperthyroid-associated hypercalcaemia crisis is rare, however, the diagnosis should pay attention to screening for other diseases caused by hypercalcemia. Timely treatment of hypercalcaemia is a critical step for rapidly control of symptoms, and treatment of hyperthyroidism is beneficial to relief the symptoms and maintain the blood calcium level.

Decreased serum and mucosa immunoglobulin A levels in vitamin Aand zinc-deficient mice

PubMed Central

Kheirouri, Sorayya

2014-01-01

Simultaneous zinc and vitamin A deficiency are common health problems in developing countries. The objective of this study was to assess the effect of vitamin A- and zinc-deficient diet on immunoglobulin A (IgA) response. Six-week-old mice were assigned into two groups receiving a normal vitamin A and zinc or low vitamin A and zinc diet for five months. Serum and intestinal mucosa IgA levels were determined by the enzyme-linked immunosorbent assay method. The concentration of zinc in serum was determined using an inductively coupled plasma mass spectrometer. Vitamin A measurement in serum was carried out by high performance liquid chromatography. Mice maintained on a low vitamin A and zinc diet showed significantly greater food intake but lower production of IgA both in serum and mucosa. A mucosa IgA level was significantly higher in both control and deficient groups than the serum IgA level. Results indicated that zinc and vitamin A deficiency is associated with a lower production of IgA. Micronutrient intervention strategies addressing IgA-related gastrointestinal infections are needed. PMID:26155118

Dietary Pyridoxine Protects against Stress and Maintains Immunohaematological Status in Chanos chanos Exposed to Endosulfan.

PubMed

Kumar, Neeraj; Ambasankar, Kondusamy; Krishnani, Kishore Kumar; Bhushan, Shashi; Minhas, Paramjit Singh

2016-09-01

The amelioration effect of water-soluble vitamin pyridoxine against stress was evaluated in milkfish, Chanos chanos exposed to endosulfan. Two hundred and twenty-five fish were distributed randomly into five treatments, each with three replicates. Four isocaloric and isonitrogenous diets with graded levels of pyridoxine feed were as follows: normal water and fed with control diet (En0/PY0); endosulfan-treated water and fed with control diet (En/PY0); and endosulfan-treated water and fed with 50 (En/PY 50 mg/kg), 75 (En/PY 75 mg/kg) and 100 mg/kg (En/PY 100 mg/kg) pyridoxine-supplemented feed. The endosulfan in treated water was maintained at a level of 1/40th of LC50 (0.52 ppb). The effect of dietary pyridoxine supplementation was studied in terms of antioxidative enzymes (catalase, superoxide dismutase, glutathione-S-transferase), stress markers [heat-shock protein 70, caspase-3, cortisol, acetylcholine esterase (AChE), blood glucose], immunohaematological parameters (total protein, albumin, globulin and A/G ratio, nitroblue tetrazolium, RBC, WBC, Hb), gill histopathology and a subsequent challenge study with Vibrio parahaemolyticus. The antioxidative enzymes, stress markers, albumin and A/G ratio were significantly (p < 0.01) elevated, brain AChE and immunohaematological parameters were significantly (p < 0.01) decreased, and chromosome aberration and gill histopathology were also altered due to endosulfan exposure. The relative survival % was reduced due to the combined effect of endosulfan stress and bacterial challenge. Fish fed the diet supplemented with pyridoxine at 75 and 100 mg/kg was found to restore the studied parameter towards normal compared with control and indicated protection against endosulfan-induced stress significantly (p < 0.01). Results obtained in the present study indicate that the supplementation of 75 and 100 mg/kg of pyridoxine in the diet has a definitive role in the mitigation of the endosulfan-induced stress in milkfish, C. chanos fingerlings. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Influence of Body Weight on Bone Mass, Architecture, and Turnover

PubMed Central

Iwaniec, Urszula T.; Turner, Russell T.

2016-01-01

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896