Home About us Contact
|
Home About us Contact | ||
|
|
||
Marked Reduction (marked + reduction)
Selected AbstractsDisruption of Cortical Microtubules by Overexpression of Green Fluorescent Protein-Tagged ,-Tubulin 6 Causes a Marked Reduction in Cell Wall SynthesisJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 1 2006David H. Burk Abstract It has been known that the transverse orientation of cortical microtubules (MTs) along the elongation axis is essential for normal cell morphogenesis, but whether cortical MTs are essential for normal cell wall synthesis is still not clear. In the present study, we have investigated whether cortical MTs affect cell wall synthesis by direct alteration of the cortical MT organization in Arabidopsis thaliana. Disruption of the cortical MT organization by expression of an excess amount of green fluorescent protein-tagged ,-tubulin 6 (GFP-TUA6) in transgenic Arabidopsis plants was found to cause a marked reduction in cell wall thickness and a decrease in the cell wall sugars glucose and xylose. Concomitantly, the stem strength of the GFP-TUA6 overexpressors was markedly reduced compared with the wild type. In addition, expression of excess GFP-TUA6 results in an alteration in cell morphogenesis and a severe effect on plant growth and development. Together, these results suggest that the proper organization of cortical MTs is essential for the normal synthesis of plant cell walls. (Managing editor: Wei Wang) [source] Reduction expression of thrombomodulin and endothelial cell nitric oxide synthase in dermatomyositisNEUROPATHOLOGY, Issue 4 2007Guang-li Shen Dermatomyositis (DM) is a systemic microvasculitis predominantly involving the capillaries. We investigated the expression of thrombomodulin (TM) and endothelial cell nitric oxide synthase (eNOS) in microvessels of DM patients. Twelve patients with acute or subacute onset of proximal muscle weakness and erythematous rash over their faces and shoulders were included in this study. Serum creatine phosphokinase was elevated in almost all patients. Electromyograph showed a myopathic pattern in all patients. Muscle biopsies were performed in all patients and 10 non-DM controls and studied with histological, enzyme histochemical and immunohistochemical staining. von Willebrand factor, TM and eNOS antibodies were used as the primary antibodies. Perifascicular degeneration and inflammatory cell infiltration in the perimysium were noted in almost all patients. Non-special esterase staining was markedly positive in capillary and microvascular endothelium. Marked reduction in TM and eNOS staining was noted in DM patients in perimysium microvessels and perifascicular area capillaries. Vascular lesions in DM were not only limited to capillaries. The low expression of TM and eNOS in microvessels suggests the anticoagulation and vasodilation functions of vascular endothelium is reduced. DM is an inflammatory vascular endothelial disease. [source] The Laser-Assisted Neck Lift: Modifications in Technique and Postoperative Care to Improve ResultsDERMATOLOGIC SURGERY, Issue 6 2002F. Richard Noodleman MD background. Conventional submental tumescent liposuction has proved disappointing for some patients with anterior neck laxity, ptotic platysma muscles, and increased subplatysmal fat. Many of these patients are facelift candidates but are unwilling to undergo this extensive procedure. We describe our hybrid approach, which offers consistently improved results and enhanced patient satisfaction. objective. To establish a sharper cervicomental angle by more completely removing subplatysmal fat. We also wished to achieve more consistent, smoother results, minimizing ripples, folds, and hematomas with a novel postoperative dressing system. methods. Extensive tumescent liposuction of the lower face, jowls, and anterior neck was performed. Following this, subplatysmal fat was removed by dissection, the platysma muscle was imbricated, and the CO2 laser utilized in a defocused, low-power mode to partially treat the dermal undersurface and underlying muscle. Our postoperative dressing included a 10 cm mineral oil polymer gel disc in the submental location, covered by tape, silicone foam, and a lower face and neck garment to provide both support and even compression over the entire neck for at least the first 24 hours. results. Results proved uniformly satisfying for most patients, even those in their senior years. Benefits included an improved cervicomental angle, a decrease in jowling, and a marked reduction in the laxity and wrinkling of the neck skin and horizontal neck creases. Problems related to postoperative rippling or folding of the redraped skin and hematoma formation were minimized. conclusion. Laser neck tightening combined with tumescent liposuction and an advanced postoperative dressing for superior support and uniform compression has resulted in consistently excellent outcomes with improved patient satisfaction. [source] Treatment of "Cyrano" Angioma with Pulsed Dye LaserDERMATOLOGIC SURGERY, Issue 7 2001Soyun Cho MD Background. Hemangiomas of the nasal tip, the so-called Cyrano nose, are often deep, disfiguring, and persistent. Objective. To evaluate the effect of treatment with pulsed dye laser on Cyrano nose. Methods. A 3-month-old boy with hemangioma of the nasal tip of 1-months duration underwent six sessions of pulsed dye laser treatment with a 7 mm collimated beam at fluences of 5.75,6.5 J/cm2, 6 weeks apart. Results. Initial improvement was noted after two treatments, and the lesion showed a marked reduction in size and improvement in color over a total treatment period of 9 months. Conclusion. Treatment with the 585 nm pulsed dye laser should be considered in the management of infants with mild to moderate degrees of nasal tip hemangiomas since it effectively reduces the lesions with minimal adverse effects. [source] The Use of Phosphatidylcholine for Correction of Lower Lid Bulging Due to Prominent Fat PadsDERMATOLOGIC SURGERY, Issue 4 2001Patrícia Guedes Rittes MDArticle first published online: 20 DEC 200 Background. Patients with prominent periorbital fat pads often complain of having a persistent "tired" look and seek treatment from their dermatologist. Objective. A non-surgical treatment of fat pads. Methods. Thirty patients were treated for prominent lower eyelid fat pads with phosphatidylcholine injection. Pre- and posttreatment photographs were taken for long-term analysis. Results. A marked reduction of the lower eyelid fat pads was noted over the 2-year follow-up period. There were no recurrences. Conclusion. The injection of phosphatidylcholine (250 mg/5 ml) into the fat pads is a simple office procedure that may postpone or even substitute for lower eyelid blepharoplasty. [source] Pod1 is required in stromal cells for glomerulogenesisDEVELOPMENTAL DYNAMICS, Issue 3 2003Shiying Cui Abstract Pod1 (capsulin/epicardin/Tcf21) is a basic-helix-loop-helix transcription factor that is highly expressed in the mesenchyme of developing organs that include the kidney, lung, gut, and heart. Null Pod1 mice are born but die shortly after birth due to a lack of alveoli in the lungs and cardiac defects. In addition, the kidneys are hypoplastic and demonstrate disrupted branching morphogenesis of the ureteric bud epithelium, a marked reduction in the number of nephrons, a delay in glomerulogenesis, and blood vessel abnormalities. To further dissect the cellular function of Pod1 during kidney development, chimeric mice were generated through aggregations of null Pod1 embryonic stem cells and murine embryos ubiquitously expressing enhanced green fluorescent protein (GFP). Histologic, immunohistochemical, and in situ hybridization analysis of the resulting chimeric offspring demonstrated both cell autonomous and non,cell autonomous roles for Pod1 in the differentiation of specific renal cell lineages that include peritubular interstitial cells and pericytes. Most strikingly, the glomerulogenesis defect was rescued by the presence of wild-type stromal cells, suggesting a non,cell autonomous role for Pod1 in this cell population. © 2003 Wiley-Liss, Inc. [source] The zebrafish ennui behavioral mutation disrupts acetylcholine receptor localization and motor axon stabilityDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2008Louis Saint-Amant Abstract The zebrafish ennui mutation was identified from a mutagenesis screen for defects in early behavior. Homozygous ennui embryos swam more slowly than wild-type siblings but normal swimming recovered during larval stages and homozygous mutants survived until adulthood. Electrophysiological recordings from motoneurons and muscles suggested that the motor output of the CNS following mechanosensory stimulation was normal in ennui, but the synaptic currents at the neuromuscular junction were significantly reduced. Analysis of acetylcholine receptors (AChRs) in ennui muscles showed a marked reduction in the size of synaptic clusters and their aberrant localization at the myotome segment borders of fast twitch muscle. Prepatterned, nerve-independent AChR clusters appeared normal in mutant embryos and dispersed upon outgrowth of motor axons onto the muscles. Genetic mosaic analysis showed that ennui is required cell autonomously in muscle fibers for normal synaptic localization of AChRs. Furthermore, exogenous agrin failed to induce AChR aggregation, suggesting that ennui is crucial for agrin function. Finally, motor axons branched more extensively in ennui fast twitch muscles especially in the region of the myotome borders. These results suggest that ennui is important for nerve-dependent AChR clustering and the stability of axon growth. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF ratsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2007Sung Hee Choi Abstract Objective To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model. Methods OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content. Results Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 ± 0.04 vs 0.88 ± 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 ± 0.4 vs 20.6 ± 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 ± 1.2 vs 18.8 ± 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement. Conclusion The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats. Copyright © 2007 John Wiley & Sons, Ltd. [source] Documenting the heroin shortage in New South WalesDRUG AND ALCOHOL REVIEW, Issue 4 2006CAROLYN DAY Abstract Australian heroin markets have recently undergone dramatic change, sparking debate about the nature of such markets. This study aimed to determine the onset, peak and decline of the heroin shortage in New South Wales (NSW), using the most appropriate available methods to detect market level changes. The parameters of the heroin shortage were determined by reviewing: reports of heroin users about availability and price (derived from the existing literature and the Illicit Drug Reporting System); qualitative interviews with injecting drug users, and health and law enforcement professionals working in the illicit drug field; and examining data on heroin seizures over the past decade. There was a marked reduction in heroin supply in NSW in early 2001. An increase in the price of heroin occurred in 2001, whereas it had decreased steadily since 1996. A reduction in purity also occurred, as reported by drug users and heroin seizures. The peak period of the shortage appears to have been January to April 2001. The market appears to have stabilised since that time, although it has not returned to pre-2001 levels: heroin prices have decreased in NSW for street grams, but not to former levels, and the price of ,caps' (street deals) remain elevated. Heroin purity in NSW has remained low, with perhaps a 10% increase above the lowest recorded levels. These data support the notion that the heroin market in NSW underwent significant changes, which appear to have involved a lasting shift in the nature of the market. [source] ,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] A Rb/Sr record of catchment weathering response to Holocene climate change in Inner MongoliaEARTH SURFACE PROCESSES AND LANDFORMS, Issue 3 2006Zhangdong Jin Abstract Variation in the rubidium to strontium (Rb/Sr) ratio of the loess,palaeosol sequences has been proposed to reflect the degree of pedogenesis and weathering in the northwestern region of China. To characterize the Rb/Sr ratio of the dissolved loads of a single catchment, we analysed a 12·08 m sediment core from Daihai Lake in Inner Mongolia, north China. Dating control was provided by 210Pb, 137Cs and AMS- 14C. Sequential extraction experiments were conducted to investigate the concentrations of Rb and Sr on various chemical fractions in the lake sediments. Down-core variation in the Rb/Sr ratios provides a record of Holocene weathering history. From 9 to 3·5 ka bp, accelerated chemical weathering was experienced throughout the Daihai catchment under mainly warm and humid conditions, and this reached a maximum at c. 5 ka bp. However, weathering was reduced between c. 8·25 and 7·90 ka bp, which may reflect the global 8·2 ka cooling event. After c. 2·5 ka bp, increased Rb/Sr ratios with higher frequency of fluctuations indicate reduced weathering within the Daihai catchment. The highest Rb/Sr ratios in the Little Ice Age lake sediments indicate the weakest phase of Holocene chemical weathering, resulting from a marked reduction in Sr flux into the basin. The Rb/Sr record also shows an enhancement of chemical weathering under today's climate, but its intensity is less than that of the Medieval Warm Period. Increased Rb/Sr in lake sediment corresponding to reduced catchment weathering is in striking contrast to Rb/Sr decrease in the glacial loess layers in the loess,palaeosol sequence. Copyright © 2005 John Wiley & Sons, Ltd. [source] Electroconductive Hydrogels: Electrical and Electrochemical Properties of Polypyrrole-Poly(HEMA) CompositesELECTROANALYSIS, Issue 7 2005Sean Brahim Abstract Composites of inherently conductive polypyrrole (PPy) within highly hydrophilic poly(2-hydroxyethyl methacrylate)-based hydrogels (p(HEMA)) have been fabricated and their electrochemical properties investigated. The electrochemical characteristics observed by cyclic voltammetry suggest less facile reduction of PPy within the composite hydrogel compared to electropolymerized PPy, as shown by the shift in the reduction peak potential from ,472,mV for electropolymerized polypyrrole to ,636,mV for the electroconductive composite gel. The network impedance magnitude for the electroconductive hydrogel remains quite low, ca. 100,,, even upon approach to DC, over all frequencies and at all offset potentials suggesting retained electronic (bipolaronic) conductivity within the composite. In contrast, sustained application of +0.7 V (vs. Ag/AgCl, 3,M Cl,) for typically 100,min. (conditioning) to reduce the background amperometric current to <1.0,,A, resulted in complete loss of electroactivity. Nyquist plots suggest that sustained application of such a modest potential to the composite hydrogel results in impedance characteristics that resembles p(HEMA) without evidence of the conducting polymer component. PPy composite gels supported a larger ferrocene monocarboxylate diffusivity (Dappt=7.97×10,5,cm2,s,1) compared to electropolymerized PPy (Dappt=5.56×10,5,cm2,s,1), however a marked reduction in diffusivity (Dappt=1.01×10,5,cm2,s,1) was observed with the conditioned hydrogel composite. Cyclic voltammograms in buffer containing H2O2 showed an absence of redox peaks for electrodes coated with PPy-containing membranes, suggesting possible chemical oxidation of polypyrrole by the oxidant [source] Responses of biofilms to combined nutrient and metal exposureENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2002Núria Ivorra Abstract Numerous studies have reported marked sensitivities of diatom species to phosphate and organic pollution but have ignored interactions with other common contaminants. The aim of the present study was to investigate the single and joint effects of increased phosphate and metal (cadmium, zinc) concentrations on benthic diatom communities. Microalgal biofilms from a relatively unpolluted stream were exposed in the laboratory to Zn, Cd, and P, separately and in combination, in concentrations found at a polluted stream in the same catchment. The Zn concentration reduced algal growth in biofilms more than the Cd concentration. Phosphate compensated for the single effect of each metal but not for their combined effects. Diatom community changes were evaluated using water quality indices based on the empirical sensitivities of taxa to nutrients (TDI) and organic pollution (%PTV). Phosphate exposure resulted in an increase of the eutrophy rank and presumed pollution-tolerant taxa. In contrast, exposure to Zn, Zn + Cd, and Zn + Cd + P caused a marked reduction of the TDI and %PTV community values. The successional trends in the laboratory matched the observed differences in microphyte communities in the reference and polluted river stations. However, the autoecology of the species present also revealed that the resulting composition of diatom communities cannot be attributed solely to the direct toxic effects of metal and nutrients and their interaction. Observed changes in the relative abundance of species are also determined by their growth form and microdistribution in biofilms. [source] Gabapentin Increases Slow-wave Sleep in Normal AdultsEPILEPSIA, Issue 12 2002Nancy Foldvary-Schaefer Summary: ,Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid-eye-movement (REM) sleep, slow-wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep. Methods: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow-up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test. Results: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP-treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects. Conclusions: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption. [source] A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosetsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Mahmoud M. Iravani Abstract Standard MPTP treatment regimens in primates result in >,85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)-positive cells, which occurred mainly in the calbindin-D28k -poor nigrosomes with a similar loss of TH-immunoreactivity (TH-ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH-ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH-ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L-DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD. [source] Degeneration of pontine mossy fibres during cerebellar development in weaver mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Miwako Ozaki Abstract In weaver mutant mice, substitution of an amino acid residue in the pore region of GIRK2, a subtype of the G-protein-coupled inwardly rectifying K+ channel, changes the properties of the homomeric channel to produce a lethal depolarized state in cerebellar granule cells and dopaminergic neurons in substantia nigra. Degeneration of these types of neurons causes strong ataxia and Parkinsonian phenomena in the mutant mice, respectively. On the other hand, the mutant gene is also expressed in various other brain regions, in which the mutant may have effects on neuronal survival. Among these regions, we focused on the pontine nuclei, the origin of the pontocerebellar mossy fibres, projecting mainly into the central region of the cerebellar cortex. The results of histological analysis showed that by P9 the number of neurons in the nuclei was reduced in the mutant to about one half and by P18 to one third of those in the wild type, whereas until P7 the number were about the same in wild-type and weaver mutant mice. Three-dimensional reconstruction of the nuclei showed a marked reduction in volume and shape of the mutant nuclei, correlating well with the decrease in neuronal number. In addition, DiI (a lipophilic tracer dye) tracing experiments revealed retraction of pontocerebellar mossy fibres from the cerebellar cortex after P5. From these results, we conclude that projecting neurons in the pontine nuclei, as well as cerebellar granule cells and dopaminergic neurons in substantia nigra, strongly degenerate in weaver mutant mice, resulting in elimination of pontocerebellar mossy fibres during cerebellar development. [source] Graduate Medical Education Downsizing: Perceived Effects of Participating in the HCFA Demonstration Project in New York StateACADEMIC EMERGENCY MEDICINE, Issue 2 2001Linda L. Spillance MD Abstract. Objective: Financial support for graduate medical education (GME) is shrinking nationally as Medicare cuts GME funds. Thirty-nine hospitals in New York State (NYS) voluntarily participated in a Health Care Financing Administration demonstration project (HCFADP),the goal of which was to reduce total residency training positions by 4-5%/year over a five-year period, while increasing primary care positions. The objective of this study was to determine the effect of downsizing on emergency department (ED) staffing and emergency medicine (EM) residency training. Methods: Structured interviews and surveys of NYS program directors (PDs) were conducted in October,December 1999. Simple frequencies are reported. Results: One hundred percent of 17 PDs completed the interviews and seven of 12 participants in the HCFADP returned surveys. Twelve of 17 programs participated in HCFADP and two programs downsized outside HCFADP. Seven of 12 participants lost EM positions. Six of 12 programs were forced to exclude outside residents from rotating in their ED, leading to a need for one participating program and one non-participating program to find alternative sites for trauma. Five of 12 institutions provided resident staffing data, reporting a reduction in ED resident coverage in year 1 of the project of 9-40%. Programs compensated by increasing the number of shifts worked (4/12), increasing shift length (1/12), decreasing pediatric ED shifts (1/12), decreasing elective or research time (2/12), and decreasing off-service rotations (4/12). Six departments hired physician assistants or nurse practitioners, two hired faculty, and two hired resident moonlighters. Six of 12 programs withdrew from HCFADP and returned to previous resident numbers. Eight of 12 PDs thought that they had decreased time for clinical teaching. Conclusions: A 4-5% reduction in residency positions was associated with a marked reduction in ED resident staffing and EM residency curriculum changes. [source] Differential Effects of Cold Exposure on Muscle Fibre Composition and Capillary Supply in Hibernator and Non-Hibernator RodentsEXPERIMENTAL PHYSIOLOGY, Issue 5 2001S. Egginton Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10 weeks of cold exposure and reduced photoperiod (10 °C, 1 h light-23 h dark). Muscle mass decreased in both species (by 12% and 17%, respectively). Following acclimation to cold there were no specific changes in fibre cross-sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 ± 0.15, normothermia, N; 1.69 ± 0.05, hypothermia, H) and average capillary density (CD) (188 ± 14 mm,2, N; 201 ± 12 mm -2, H). Similarly, the average C:F was unaltered in hamsters (2.75 ± 0.11, N; 2.72 ± 0.15, H), although the 30% smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 ± 80 mm,2 (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 ,m2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 ,m2, N; 846 ,m2, H; n.s.) but a marked reduction in the core (871 ,m2, N; 604 ,m2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy. [source] Caveolin-1 influences P2X7 receptor expression and localization in mouse lung alveolar epithelial cellsFEBS JOURNAL, Issue 12 2007K. Barth The P2X7 receptor has recently been described as a marker for lung alveolar epithelial type I cells. Here, we demonstrate both the expression of P2X7 protein and its partition into lipid rafts in the mouse lung alveolar epithelial cell line E10. A significant degree of colocalization was observed between P2X7 and the raft marker protein Caveolin-1; also, P2X7 protein was associated with caveolae. A marked reduction in P2X7 immunoreactivity was observed in lung sections prepared from Caveolin-1-knockout mice, indicating that Caveolin-1 expression was required for full expression of P2X7 protein. Indeed, suppression of Caveolin-1 protein expression in E10 cells using short hairpin RNAs resulted in a large reduction in P2X7 protein expression. Our data demonstrate a potential interaction between P2X7 protein and Caveolin-1 in lipid rafts, and provide a basis for further functional and biochemical studies to probe the physiologic significance of this interaction. [source] A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patientsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2003M. T. Khayyal Abstract The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of >,15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2,5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19,52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19% increase in FVC, a 29.5% increase in FEV1, a 30% increase in peak expiratory flow rate (PEFR), and a 41% increase in the forced expiratory flow rate between 25 and 75% of the vital capacity (FEF25-75). The clinical improvement was associated with decreases by 52, 65, 44 and 30%, respectively, of initial values for the pro-inflammatory cytokines tumor necrosis factor (TNF)-,, ICAM-1, interleukin (IL)-6 and IL-8, and a 3-fold increase in the ,protective' cytokine IL-10. The levels of prostaglandins E2 and F2, and leukotriene D4 were decreased significantly to 36, 39, and 28%, respectively, of initial values. Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators. The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients. The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents. [source] Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membraneGLIA, Issue 6 2008Patrice E. Fort Abstract The dystrophin-associated proteins (DAPs) complex consisting of dystroglycan, syntrophin, dystrobrevin, and sarcoglycans in muscle cells is associated either with dystrophin or its homolog utrophin. In rat retina, a similar complex was found associated with dystrophin-Dp71 that serves as an anchor for the inwardly rectifying potassium channel Kir4.1 and the aqueous pore, aquaporin-4 (AQP4). Here, using immunofluorescence imaging of isolated retinal Müller glial cells and co-immunoprecipitation experiments performed on an enriched Müller glial cells end-feet fraction, we investigated the effect of Dp71 deletion on the composition, anchoring, and membrane localization of the DAPs,Kir4.1 and/or ,AQP4 complex. Two distinct complexes were identified in the end-feet fraction associated either with Dp71 or with utrophin. Upon Dp71 deletion, the corresponding DAPs complex was disrupted and a compensating utrophin upregulation was observed, accompanied by diffuse overall staining of Kir4.1 along the Müller glial cells and redistribution of the K+ conductance. Dp71 deficiency was also associated with a marked reduction of AQP4 and ,-dystroglycan expression. Furthermore, it was observed that the Dp71,DAPs dependent complex could be, at least partially, associated with a specific membrane fraction. These results demonstrate that Dp71 has a central role in the molecular scaffold responsible for anchoring AQP4 and Kir4.1 in Müller cell end-feet membranes. They also show that despite its close relationship to the dystrophin proteins and its correlated upregulation, utrophin is only partially compensating for the absence of Dp71 in Müller glial cells. © 2008 Wiley-Liss, Inc. [source] Utilization of semi-natural grassland through integrated generation of solid fuel and biogas from biomass.GRASS & FORAGE SCIENCE, Issue 4 2009Abstract A procedure (Integrated Generation of Solid Fuel and Biogas from Biomass, IFBB) was developed which uses a screw press to separate the readily digestible constituents of mature grassland biomass into a press fluid for conversion into biogas and a fibrous press cake for processing into a solid fuel. Effects of mechanical dehydration and prior hydrothermal conditioning at different temperatures (5, 60 and 80°C) on concentrations of organic compounds in the press fluid and on methane production in batch experiments were evaluated for five semi-natural grasslands typical of mountain areas of Germany. Results show that the crude protein concentration of the press fluids was higher and crude fibre concentration was lower than that of the parent material (herbage conserved as silage). Digestion tests in batch fermenters showed that the methane yield of the press fluids was double [397,426 normal litre (NL) kg,1 volatile solids (VS) after 13 d] that of the whole-crop grassland silage (218 NL kg,1 VS after 27 d) but no consistent effect of higher temperature during conditioning was observed. Within 13 d of fermentation the decomposition of the organic matter (OM) that occurred in the press fluids was 0·90, whereas after 27 d of fermentation more than 0·40 of the OM remained undigested in the whole-crop silage, pointing at a marked reduction in retention time for anaerobic digestion of press fluids in continuous systems. Press fluids produced 0·90 of the maximum methane yield after 4 to 7 d compared with 19 days for the whole-crop silage. [source] SAFE biopsy: A validated method for large-scale staging of liver fibrosis in chronic hepatitis C,HEPATOLOGY, Issue 6 2009Giada Sebastiani The staging of liver fibrosis is pivotal for defining the prognosis and indications for therapy in hepatitis C. Although liver biopsy remains the gold standard, several noninvasive methods are under evaluation for clinical use. The aim of this study was to validate the recently described sequential algorithm for fibrosis evaluation (SAFE) biopsy, which detects significant fibrosis (,F2 by METAVIR) and cirrhosis (F4) by combining the AST-to-platelet ratio index and Fibrotest-Fibrosure, thereby limiting liver biopsy to cases not adequately classifiable by noninvasive markers. Hepatitis C virus (HCV) patients (2035) were enrolled in nine locations in Europe and the United States. The diagnostic accuracy of SAFE biopsy versus histology, which is the gold standard, was investigated. The reduction in the need for liver biopsies achieved with SAFE biopsy was also assessed. SAFE biopsy identified significant fibrosis with 90.1% accuracy (area under the receiver operating characteristic curve = 0.89; 95% confidence interval, 0.87-0.90) and reduced by 46.5% the number of liver biopsies needed. SAFE biopsy had 92.5% accuracy (area under the receiver operating characteristic curve = 0.92; 95% confidence interval, 0.89-0.94) for the detection of cirrhosis, obviating 81.5% of liver biopsies. A third algorithm identified significant fibrosis and cirrhosis simultaneously with high accuracy and a 36% reduction in the need for liver biopsy. The patient's age and body mass index influenced the performance of SAFE biopsy, which was improved with adjusted Fibrotest-Fibrosure cutoffs. Two hundred two cases (9.9%) had discordant results for significant fibrosis with SAFE biopsy versus histology, whereas 153 cases (7.5%) were discordant for cirrhosis detection; 71 of the former cases and 56 of the latter cases had a Fibroscan measurement within 2 months of histological evaluation. Fibroscan confirmed SAFE biopsy findings in 83.1% and 75%, respectively. Conclusion: SAFE biopsy is a rational and validated method for staging liver fibrosis in hepatitis C with a marked reduction in the need for liver biopsy. It is an attractive tool for large-scale screening of HCV carriers. (HEPATOLOGY 2009.) [source] Llama-derived single-domain intrabodies inhibit secretion of hepatitis B virions in mice,HEPATOLOGY, Issue 1 2009Benedikte Serruys Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single-domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV. VHHs, when expressed and retained in the endoplasmic reticulum as intrabodies, reduced levels of secreted hepatitis B surface antigen (HBsAg) particles in a cellular HBV model. In a hydrodynamics-based HBV mouse model, these intrabodies caused a marked reduction in HBsAg concentrations and a 10- to >100-fold reduction in the concentration of HBV virions in plasma. Conclusion: VHHs potently inhibited secretion of HBV virions in vivo, showing that this approach might be useful in the treatment of HBV. To our knowledge, this is the first report of intrabody-mediated inhibition of viral secretion in mammals. (HEPATOLOGY 2009;49:39-49.) [source] Decomposition of litter in a dry sclerophyll eucalypt forest and a Pinus radiata plantation in southeastern AustraliaHYDROLOGICAL PROCESSES, Issue 17 2002R. H. Crockford This study of litter decomposition was part of an extensive project examining the partitioning of rainfall, the associated chemistry, and litterfall in a dry sclerophyll eucalypt forest and a Pinus radiata plantation in southeastern Australia. The eucalypt species studied were Eucalyptus rossii, E. mannifera and E. dives. The components tested were Pinus radiata needles, leaves of the three eucalypt species, and the bark of E. rossii and E. mannifera. During the first 16 weeks of the decomposition experiment there was a rapid decrease in the concentrations of potassium, magnesium, sodium and phosphorus; this was attributed to leaching. During this period, concentrations of nitrogen and calcium increased for most components. After this period, decomposition became the dominant process, during which the concentrations of most elements increased. By the end of the experiment there was, compared with the initial values, a marked reduction in concentrations of sodium, magnesium and potassium for all eucalypt and pine litter. Calcium concentrations increased through time, with eucalypt bark showing a mid-period decline. Phosphorus concentrations decreased for the eucalypt leaves but increased substantially for the pine needles and the eucalypt bark. For all components of both the eucalypts and pines, total nitrogen concentrations rose consistently throughout the decomposition period. This was attributed to the formation of nitrogen-substituted lignin, which was more resistant to decomposition than the other nitrogen-containing compounds, as well as some nitrogen being stored in the micro-organisms responsible for decomposition. Because of loss of fragmented litter from the litter bags after 16 weeks, the weight changes could not be confidently measured after this period. Copyright © 2002 John Wiley & Sons, Ltd. [source] Decay-accelerating factor induction by tumour necrosis factor-,, through a phosphatidylinositol-3 kinase and protein kinase C-dependent pathway, protects murine vascular endothelial cells against complement depositionIMMUNOLOGY, Issue 2 2003Saifur R. Ahmad Summary We have shown that human endothelial cells (EC) are protected against complement-mediated injury by the inducible expression of decay-accelerating factor (DAF). To understand further the importance of DAF regulation, we characterized EC DAF expression on murine EC in vitro and in vivo using a model of glomerulonephritis. Flow cytometry using the monoclonal antibody (mAb) Riko-3 [binds transmembrane- and glycosylphosphatidylinositol (GPI)-anchored DAF], mAb Riko-4 (binds GPI-anchored DAF) and reverse transcription,polymerase chain reaction (RT,PCR), demonstrated that murine EC DAF is GPI-anchored. Tumour necrosis factor-, (TNF-,) increased EC DAF expression, detectable at 6 hr and maximal at 24,48 hr poststimulation. DAF upregulation required increased steady-state DAF mRNA and protein synthesis. In contrast, no increased expression of the murine complement receptor-related protein-Y (Crry) was seen with TNF-,. DAF upregulation was mediated via a protein kinase C (PKC),, phosphoinositide-3 kinase (PI-3 kinase), p38 mitogen-activated protein kinase (MAPK) and nuclear factor-,B (NF-,B)-dependent pathway. The increased DAF was functionally relevant, resulting in a marked reduction in C3 deposition following complement activation. In a nephrotoxic nephritis model, DAF expression on glomerular capillaries was significantly increased 2 hr after the induction of disease. The demonstration of DAF upregulation above constitutive levels suggests that this may be important in the maintenance of vascular integrity during inflammation, when the risk of complement-mediated injury is increased. The mouse represents a suitable model for the study of novel therapeutic approaches by which vascular endothelium may be conditioned against complement-mediated injury. [source] The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's diseaseINTERNAL MEDICINE JOURNAL, Issue 1 2000K. A. Reardon Abstract Background: Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. Aims: We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease. Results: After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in ,on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more ,on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction. Conclusions: These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study. [source] Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2005J. L. Brzezinski Summary The polymorphic T-cell receptor V, (TRBV) genes encode much of the variable region of the T-cell receptor , chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus. [source] Phytase production by Sporotrichum thermophile in a cost-effective cane molasses medium in submerged fermentation and its application in breadJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2008B. Singh Abstract Aims:, Phytase production by Sporotrichum thermophile in a cost-effective cane molasses medium in submerged fermentation and its application in bread. Methods and Results:, The production of phytase by a thermophilic mould S. thermophile was investigated using free and immobilized conidiospores in cane molasses medium in shake flasks, and stirred tank and air-lift fermenters. Among surfactants tested, Tweens (Tween-20, 40 and 80) and sodium oleate increased phytase accumulation, whereas SDS and Triton X-100 inhibited the enzyme production. The mould produced phytase optimally at aw 0·95, and it declined sharply below this aw value. The enzyme production was comparable in air-lift and stirred tank reactors with a marked reduction in fermentation time. Among the matrices tried, Ca-alginate was the best for conidiospore immobilization, and fungus secreted sustained levels of enzyme titres over five cycles. The phytic acid in the dough was efficiently hydrolysed by the enzyme accompanied by the liberation of soluble phosphate in the bread. Conclusions:, The phytase production by S. thermophile was enhanced in the presence of Tween-80 in cane molasses medium. A peak in enzyme production was attained in 48 h in the fermenter when compared with that of 96 h in shake flasks. Ca-alginate immobilized conidiospores germinated to produce fungal growth that secreted sustained levels of phytase over five cycles. The bread made with phytase contained reduced level of phytic acid and a high-soluble phosphate. Significance and Impact of the Study:, The phytase accumulation by S. thermophile was increased by the surfactants. The sustainability of enzyme production in stirred tank and air-lift fermenters suggested the possibility for scaling up of phytase. The bread made with phytase contained low level of antinutrient, i.e. phytic acid. [source] OmpA is an adhesion factor of Aeromonas veronii, an optimistic pathogen that habituates in carp intestinal tractJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2008A. Namba Abstract Aims:, In the present study, we focused on one of the Aeromonas veronii isolates that exhibited marked adhesion onto carp intestine and studied its membrane-associated proteins for their possible involvement in mucosal adhesion. Methods and Results:, We isolated a strain of Aer. veronii (CWP11) that exhibited a high degree of temperature-dependent adhesion activity onto carp intestinal tract and studied its adhesion factor. A proteomic analysis of the membrane-associated fraction showed the presence of multiple proteins that were specifically expressed in CWP11 cells cultured at 25°C. Of these, a 30 kDa protein was identified to be OmpA by a mass fingerprint analysis. Cloning and nucleotide sequencing of the ompA region of CWP11 revealed the presence of two tandem ompA homologues (ompAI - ompAII). Escherichia coli that expressed either OmpAI or OmpAII exhibited marked adhesion onto carp intestinal surface. Disruption of ompAI by a homologous recombination technique resulted in marked reduction of the adhesion activity in CWP11. Conclusion:, The OmpA homologue plays an important role in the adhesion of the Aer. veronii strain onto the surface of intestinal tract. Significance and Impact of the Study:, We successfully identified an OmpA homologue to be an adhesion factor of Aer. veronii, an optimistic pathogen that habituates in carp intestinal tract. [source] | ||||||||||||||||||||||||||||||||||||||||||||||