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1.
Phys Rev E ; 107(6-2): 065209, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37464717

ABSTRACT

Using three-dimensional (3D) magnetohydrodynamic simulations, we study how a pit on a metal surface evolves when driven by intense electrical current density j. Redistribution of j around the pit initiates a feedback loop: j both reacts to and alters the electrical conductivity σ, through Joule heating and hydrodynamic expansion, so that j and σ are constantly in flux. Thus, the pit transforms into larger striation and filament structures predicted by the electrothermal instability theory. Both structures are important in applications of current-driven metal: The striation constitutes a density perturbation that can seed the magneto-Rayleigh-Taylor instability, while the filament provides a more rapid path to plasma formation, through 3D j redistribution. Simulations predict distinctive self-emission patterns, thus allowing for experimental observation and comparison.

2.
Phys Rev Lett ; 130(25): 255101, 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37418744

ABSTRACT

Electrothermal instability plays an important role in applications of current-driven metal, creating striations (which seed the magneto-Rayleigh-Taylor instability) and filaments (which provide a more rapid path to plasma formation). However, the initial formation of both structures is not well understood. Simulations show for the first time how a commonly occurring isolated defect transforms into the larger striation and filament, through a feedback loop connecting current and electrical conductivity. Simulations have been experimentally validated using defect-driven self-emission patterns.


Subject(s)
Cytoskeleton , Plasma
3.
Rev Sci Instrum ; 94(3): 031102, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37012753

ABSTRACT

The Z machine is a current driver producing up to 30 MA in 100 ns that utilizes a wide range of diagnostics to assess accelerator performance and target behavior conduct experiments that use the Z target as a source of radiation or high pressures. We review the existing suite of diagnostic systems, including their locations and primary configurations. The diagnostics are grouped in the following categories: pulsed power diagnostics, x-ray power and energy, x-ray spectroscopy, x-ray imaging (including backlighting, power flow, and velocimetry), and nuclear detectors (including neutron activation). We will also briefly summarize the primary imaging detectors we use at Z: image plates, x-ray and visible film, microchannel plates, and the ultrafast x-ray imager. The Z shot produces a harsh environment that interferes with diagnostic operation and data retrieval. We term these detrimental processes "threats" of which only partial quantifications and precise sources are known. We summarize the threats and describe techniques utilized in many of the systems to reduce noise and backgrounds.

4.
Int Nurs Rev ; 68(3): 420-433, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32893345

ABSTRACT

BACKGROUND: Information and communication technologies have become omnipresent in healthcare systems globally, and since nurses comprise the majority of the health sector workforce, they are expected to be adequately skilled to work in a technology-mediated environment. Integrating nursing informatics into undergraduate nursing education is a cornerstone to nursing education and practice in Africa. AIM: This scoping review aimed to evidence the integration of nursing informatics into undergraduate nursing education in Africa. METHODS: A scoping review of the literature used electronic databases including CINAHL Plus databases; EmCare; MEDLINE Ovid; Scopus; ERIC ProQuest; Web of Science; Google; and Google Scholar to locate papers specific to the African context. From a total of 8723 articles, 19 were selected for critique and synthesis. RESULTS: Selected studies indicated that nursing students used several information and communication technologies tools primarily for academic purposes, and rarely for clinical practice. In Africa, the challenges for teaching informatics in nursing education included: limited information and communication technologies skills among faculty and students; poor teaching strategies; and a lack of standardization of nursing informatics competencies. Successful integration of nursing informatics into undergraduate nursing education in African countries depends on restructuring nursing informatics content and teaching strategies, capacity building of the faculty and students in information and communication technologies, political commitment, and collaborative partnership. CONCLUSION: Nursing informatics is scarce in undergraduate nursing education in Africa due to the implementation and adoption challenges. Responding to these challenges requires a multi-sectoral approach in the revision of undergraduate nursing curricula. IMPLICATION FOR NURSING EDUCATION, PRACTICE, POLICY AND RESEARCH: This study highlights the importance of nursing informatics in undergraduate nursing education, with its challenges and success. Nursing education policies should support the development of well-standardized nursing informatics content and appropriate teaching strategies to deliver it. Further research is needed to establish which aspects of nursing informatics are integrated into undergraduate nursing education and nursing practice, implementation process, challenges and possible solutions. Collaborative partnerships are vital to developing nursing informatics policies to better prepare graduate nurses for the African healthcare workforce in the digital era.


Subject(s)
Education, Nursing, Baccalaureate , Education, Nursing , Nursing Informatics , Students, Nursing , Curriculum , Humans
5.
J Environ Manage ; 278(Pt 2): 111545, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33202370

ABSTRACT

Marine spatial planning (MSP) has rapidly become the most widely used integrated, place-based management approach in the marine environment. Monitoring and evaluation of MSP is key to inform best practices, adaptive management and plan iteration. While standardised evaluation frameworks cannot be readily applied, accounting for evaluation essentials such as the definition of evaluation objectives, indicators and stakeholder engagement of stakeholders is a prerequisite for meaningful evaluation outcomes. By way of a literature review and eleven practical MSP case studies, we analysed present day trends in evaluation approaches and unravelled the adoption of evaluation essentials for three categories for monitoring and evaluation for plan making, plan outcomes, and policy implementation. We found that at a global scale the focus of MSP evaluation has shifted over the past decade from evaluating predominantly plan outcomes towards the evaluation of plan making. Independent of the scope of the evaluation, evaluation approaches varied greatly from formal and structured processes, building for instance on MSP goals and objectives, to informal processes based on stakeholder interviews. We noted a trend in the adoption of formalised approaches where MSP evaluations have increasingly become linked to MSP policy goals and objectives. However, the enhanced use of MSP objectives and indicators did not result in a more straightforward reporting of outcomes, e.g. such as the achievement of specific MSP objectives. Overall, we found weak linkages between defined MSP objectives, indicators and available monitoring data. While the apparent shift towards a focus on objectives is promising, we highlight the need of fit-for-purpose monitoring data to enable effective evaluation of those objectives. Hence, effective MSP and adaptive management processes require customised and concurrent monitoring and evaluation strategies and procedures. We argue that evaluation processes would also benefit from a better understanding of the general environmental, socio-economic and socio-cultural effects of MSP. Therefore, to understand better environmental effects of MSP, we praise that forthcoming MSP processes need to deepen the understanding and considerations of cause-effect pathways between human activities and changes of ecosystem state through the adoption of targeted cumulative effects assessments.


Subject(s)
Conservation of Natural Resources , Ecosystem , Human Activities , Humans
6.
Anim Genet ; 50(3): 271-274, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31006892

ABSTRACT

Variations in the SLC45A2 gene are responsible for the dilution phenotypes cream and pearl in domestic horses. Cream dilution is inherited in an incomplete dominant manner, diluting only red in the heterozygous state but both red and black pigments when two alleles are present. The pearl dilution is recessive and dilutes only the red and black pigment in the homozygous state or when paired with a cream allele. Horses that inherit one copy of pearl (Cprl ) and one copy of the dominant cream allele (CC r ) display a dilution phenotype similar to that of homozygous cream, suggesting that pearl is the result of a different variation in the same gene responsible for cream. We sequenced SLC45A2 in two 'false double dilute' horses that appeared phenotypically homozygous cream but tested as possessing only a single CC r allele. We also sequenced one known pearl carrier to screen for putative causal variants. The missense variant ECA21:SLC45A2:c.985G>A; p.Ala329Thr (Cprl ) was present in one false double dilute and the pearl carrier and was also genotyped in an additional 126 horses for statistical evaluation. The genotype matched the expected phenotype in all horses (P-value = 6.5 × 10-41 ) and is identical to a pearl variant found previously. The second false double dilute horse and one non-dilute offspring genotyped as heterozygous for a novel missense variant ECA21:SLC45A2:c.568G>A (p.Gly190Arg), the proposed Csun variant (for the name of the horse). This variant produces a recessive dilution similar to pearl and indicates that multiple alleles of SLC45A2 result in dilution phenotypes in the domestic horse.


Subject(s)
Hair Color , Horses/genetics , Membrane Transport Proteins/genetics , Animals , Heterozygote , Pigmentation
7.
Phys Rev E ; 97(5-1): 053208, 2018 May.
Article in English | MEDLINE | ID: mdl-29906862

ABSTRACT

A direct observation of the stratified electrothermal instability on the surface of thick metal is reported. Aluminum rods coated with 70µm Parylene-N were driven to 1 MA in 100ns, with the metal thicker than the skin depth. The dielectric coating suppressed plasma formation, enabling persistent observation of discrete azimuthally correlated stratified thermal perturbations perpendicular to the current whose wave numbers, k, grew exponentially with rate γ(k)=0.06ns^{-1}-(0.4ns^{-1}µm^{2}rad^{-2})k^{2} in ∼1g/cm^{3}, ∼7000K aluminum.

8.
N Engl J Med ; 374(19): 1842-1852, 2016 May 12.
Article in English | MEDLINE | ID: mdl-27168434

ABSTRACT

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Asthma/physiopathology , Lung/physiology , Administration, Inhalation , Adolescent , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Budesonide/therapeutic use , Child , Child, Preschool , Female , Forced Expiratory Volume , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Lung/growth & development , Male , Nedocromil/therapeutic use , Risk Factors , Sex Factors , Spirometry , Young Adult
9.
Neurogastroenterol Motil ; 28(7): 1001-15, 2016 07.
Article in English | MEDLINE | ID: mdl-26946489

ABSTRACT

BACKGROUND: In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients. METHODS: Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes. KEY RESULTS: At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life. CONCLUSIONS & INFERENCES: Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.


Subject(s)
Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Gastroparesis/diagnosis , Gastroparesis/epidemiology , Adult , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Female , Follow-Up Studies , Gastroparesis/physiopathology , Humans , Male , Middle Aged , Quality of Life , Registries , Treatment Outcome
10.
Phys Rev E Stat Nonlin Soft Matter Phys ; 86(3 Pt 2): 036412, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23031038

ABSTRACT

Laser probe diagnostics: shadowgraphy, interferometry, and polarimetry were used for a comprehensive characterization of ionization wave dynamics inside a glass target induced by a laser-driven, relativistic electron beam. Experiments were done using the 50-TW Leopard laser at the University of Nevada, Reno. We show that for a laser flux of ∼2 × 10(18) W/cm2 a hemispherical ionization wave propagates at c/3 for 10 ps and has a smooth electron-density distribution. The maximum free-electron density inside the glass target is ∼2 × 10(19) cm-3, which corresponds to an ionization level of ∼0.1%. Magnetic fields and electric fields do not exceed ∼15 kG and ∼1 MV/cm, respectively. The electron temperature has a hot, ringlike structure with a maximum of ∼0.7 eV. The topology of the interference phase shift shows the signature of the "fountain effect", a narrow electron beam that fans out from the propagation axis and heads back to the target surface. Two-dimensional particle-in-cell (PIC) computer simulations demonstrate radial spreading of fast electrons by self-consistent electrostatic fields driven by laser. The very low ionization observed after the laser heating pulse suggests a fast recombination on the sub-ps time scale.


Subject(s)
Electrons , Glass/chemistry , Glass/radiation effects , Lasers , Models, Theoretical , Computer Simulation , Electric Conductivity , Light , Scattering, Radiation
11.
Int J Lab Hematol ; 34(4): 396-402, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22348286

ABSTRACT

INTRODUCTION: Cancers are associated with varying degrees of an increased risk of venous thromboembotic events (VTE) occurring. This increased risk is tumour driven and associated with tumour expression of tissue factor (TF) and tumour-derived microparticles (MP). In this study, cancer cell lines from phenotypically distinct tumours were assessed for cell surface TF expression and prothrombin time (PT) taken as a measure of procoagulant potential. METHODS: Breast (T47D, MCF-7), colorectal (Colo320 and LoVo), head and neck (USCC 11b, 12, 81b and SIHN-011A) and pancreatic tumour cell lines (ASPC-1 and CFPAC-1) were assessed for TF expression by flow cytometry and relative mean fluorescence determined. Procoagulant potential of the cells was then determined by PT assay. RESULTS: Cell-supported coagulation was shown to be cell number dependent, defined by a logarithmic relationship that was consistent across all cell lines. Single cell PT was determined for each cell line from the slope of a logarithmically transformed data plot. A near linear relationship was observed between TF expression and single cell clotting time where a higher expression of TF results in a proportionally faster PT (P < 0.001). CONCLUSIONS: This study shows that across a range of tumour sites a consistent relationship is seen between procoagulant potential and both cell number and TF cell surface expression.


Subject(s)
Gene Expression Regulation , Neoplasms/metabolism , Thromboplastin/metabolism , Cell Aggregation/genetics , Cell Line, Tumor , Flow Cytometry , Humans , Neoplasms/physiopathology , Prothrombin Time , Thromboplastin/genetics
12.
Environ Pollut ; 159(2): 416-22, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21074917

ABSTRACT

Muscle tissue was collected from ewes and lambs derived from farms throughout Scotland and sample concentrations of five endocrine disrupting compound groups were determined. Farms of origin were categorised according to geographic region. There were few statistically-significant differences with region or distance from cities. However, the magnitude of the difference between the highest and lowest mean values in ewe muscle from different regions exceeded 30% for 13 of the 15 compounds that were consistently detected in muscle, with animals derived from the industrialised region having the highest mean values for 11 of the 13 compounds. A less marked trend was apparent in the lamb muscle (8 of 13 highest were in the industrialised region). The physiological effects of such small differences in exposure to mixtures of pollutants remain to be determined.


Subject(s)
Endocrine Disruptors/analysis , Endocrine Disruptors/metabolism , Environmental Pollutants/analysis , Environmental Pollutants/metabolism , Muscle, Skeletal/metabolism , Sheep/metabolism , Animals , Female , Muscle, Skeletal/chemistry , Scotland
13.
Phys Rev Lett ; 102(22): 227201, 2009 Jun 05.
Article in English | MEDLINE | ID: mdl-19658897

ABSTRACT

The scaling exponent of 1.6 between anomalous Hall and longitudinal conductivity, characteristic of the universal Hall mechanism in dirty-metal ferromagnets, emerges from a series of CrO2 films as we systematically increase structural disorder. Magnetic disorder in CrO2 increases with temperature and this drives a separate topological Hall mechanism. We find that these terms are controlled discretely by structural and magnetic defect populations, and their coexistence leads to apparent divergence from exponent 1.6, suggesting that the universal term is more prevalent than previously realized.

14.
Complement Ther Med ; 17(4): 224-8, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19632550

ABSTRACT

OBJECTIVES: To determine the percentage of Emergency Medicine patients using Complementary Therapies (CTs), to investigate what types of CTs are used most commonly, and to gauge the acceptability of studies of CT effectiveness in a hospital setting. METHOD: Prospective cross sectional survey using a convenience sample of adult patients, presenting to the Emergency Care Centre at North Shore Hospital in Auckland, New Zealand between December 2004 and March 2006. The survey questionnaire collected demographic data, information on CT usage and attitudes to studies of CTs. Descriptive statistics with 95% confidence intervals are reported. Comparisons of proportions were made using Chi-Square or Fisher exact. RESULTS: 56.1% of participants had used a CT. Vitamins and minerals (21.2%), massage (13.4%), acupuncture (10.6%) were the most commonly used CTs. 53.3% of those using herbs or complementary medicines had not told their doctor. When compared to those who had not used CTs, respondents who had previously used CTs were both more likely to follow their doctor's advice to use a CT (71.7% vs. 55.3%, p=0.0035), and to participate in a study of CT effectiveness (65.0% vs. 45.4%, p=0.0007). CONCLUSIONS: More than half the patients surveyed had used CT in the past and more than half had not told their doctor. The majority of Emergency Medicine patients would follow the advice of their doctor if a CT was advised, and would agree to participate in a study of CT effectiveness, suggesting that such studies are practical in a hospital setting.


Subject(s)
Complementary Therapies/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Patient Acceptance of Health Care , Acupuncture Therapy , Adolescent , Adult , Aged , Chi-Square Distribution , Confidence Intervals , Cross-Sectional Studies , Directive Counseling , Female , Humans , Male , Massage , Middle Aged , Minerals/therapeutic use , New Zealand , Prospective Studies , Self Disclosure , Vitamins/therapeutic use , Young Adult
15.
Rev. chil. neuro-psiquiatr ; 47(1): 9-15, mar. 2009. ilus
Article in Spanish | LILACS | ID: lil-554885

ABSTRACT

Benzodiazepines are a group of major therapeutic drugs, but its abuse is associated with dependence and other adverse effects. Its great for self consumption during the decade 1980-1989, led the health authority to establish in 1993 the control of prescribing and dispensing. The aim of this study was to determine the trend of use of these drugs by the population that goes to pharmacies. To that end, we examined the prescriptions dispensed for a period for three months covering the years 2003 and 2007, private pharmacies in the center of Concepción, and supplemented with information gathered randomly using questionnaires to patients who attended these pharmacies. The variables were considered among others gender, reason for the prescription, a specialist prescribed, dispensed drugs. The results indicated that women were the most used them (72 percent). The reason for prescription was predominantly anxiolytic and hypnotic effects. General practitioners, psychiatrists and neurologists prescribed the drugs (45 percent, 23 percent and 12 percent), respectively. Data that correspond to work performed in 1988 in Concepción. Among the drugs dispensed, clonazepam, alprazolam and lorazepam. It can be concluded that benzodiazepines are a group widely used in clinical treatment, and that trend continues over time, despite the implementation of the control of the prescription.


Las benzodiazepinas constituyen un grupo de fármacos de gran importancia terapéutica, pero su abuso se asocia a dependencia y a otros efectos adversos. Su gran consumo por automedicación durante la década 1980-1989, llevó a la autoridad sanitaria a establecer en el año 1993 el control de su prescripción y dispensación. El objetivo de este estudio fue determinar la tendencia de utilización de estos medicamentos por la población que acude a las farmacias. Para ello se analizaron las recetas dispensadas durante un período de tres meses los años 2003 y 2007 en farmacias privadas del centro de la ciudad de Concepción y se complementó con la información recabada al azar mediante cuestionario a pacientes que concurrieron a dichas farmacias. Las variables consideradas fueron entre otras, género, motivo de la prescripción, especialista que prescribe, fármacos más dispensados. Los resultados indicaron que las mujeres fueron las que más las utilizaron (70 por ciento). El motivo de prescripción fue mayoritariamente por los efectos hipnótico y ansiolítico. Los especialistas que más los prescribieron fueron médicos generales (45 por ciento), psiquiatras (23 por ciento) y neurólogos (12 por ciento). Datos que se corresponden con trabajos realizados en el año 1988 en Concepción. Entre los fármacos más dispensados, clonazepam, alprazolam y lorazepam. Se puede concluir que las benzodiazepinas son un grupo terapéutico muy utilizado en clínica, y que la tendencia se mantiene a través del tiempo a pesar de la implementación del control de la prescripción.


Subject(s)
Humans , Male , Female , Benzodiazepines/therapeutic use , Drug and Narcotic Control , Drug Prescriptions , Pharmacies , Private Sector , Drug Utilization/trends , Anti-Anxiety Agents/therapeutic use , Self Medication/trends , Chile , Sex Distribution , Surveys and Questionnaires
16.
Clin Nephrol ; 67(3): 176-81, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17390742

ABSTRACT

There is no known clinical association between chronic myelogenous leukemia (CML) and membranoproliferative glomerulonephritis (MPGN). We present a patient who was followed in the renal clinic for proteinuria of unknown etiology (3.2 g/24 h) and normal renal function who was diagnosed with CML as well as MPGN and acute renal failure at the same time. The patient's renal function and proteinuria improved when his CML was treated with imatinib mesylate, suggesting that CML either caused or exacerbated existing MGPN. To the best of our knowledge, this is the first reported case of MPGN associated with CML that improved with imatinib mesylate therapy.


Subject(s)
Glomerulonephritis, Membranoproliferative/etiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Benzamides , Biopsy , Bone Marrow/pathology , Disease Progression , Follow-Up Studies , Glomerular Basement Membrane/ultrastructure , Glomerulonephritis, Membranoproliferative/drug therapy , Glomerulonephritis, Membranoproliferative/pathology , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Mesangial Cells/ultrastructure , Microscopy, Electron , Middle Aged , Protein-Tyrosine Kinases/antagonists & inhibitors
17.
Osteoarthritis Cartilage ; 15(2): 147-54, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16908205

ABSTRACT

OBJECTIVE: Although Wnt signaling is a key regulator of the chondrocyte life cycle during embryonic development, little is known about Wnt activity in articular cartilage. Recent studies have suggested an association between excess signaling through the canonical Wnt pathway and osteoarthritis (OA). Genetic and in vitro studies with Drosophila have shown that signaling by the orthologous protein, Wingless (Wg), is regulated by glycosaminoglycans (GAGs) found at the cell surface. The objective of this study was to determine whether alteration in GAG sulfation or matrix content, such as that occurs in OA cartilage, would affect articular chondrocytes' response to a canonical Wnt stimulus. METHODS: Cells were isolated from shoulder joints of young calves (bovine articular chondrocytes, bACs) and from human cartilage (human articular chondrocytes, hACs) discarded during total knee replacement for OA. Conditioned media from a cell line that is stably transfected with Wnt3a was used as a source of Wnt protein that activates the canonical signaling pathway. Conditioned media from the parental cell line was used as a control. beta-catenin levels were measured by immunoblot. In some experiments, chondrocyte cultures were treated with sodium chlorate (NaClO3) to inhibit GAG sulfation, or with chondroitinase ABC (ChABC) to digest chondroitin sulfate (CS) in the matrix. RESULTS: Cultured bACs showed low steady-state levels of beta-catenin that increased upon stimulation with Wnt3a. A decrease in either GAG sulfation or CS content diminished bACs' response to Wnt3a (approximately 40% and 37% of control, respectively). Similar effects on the response to Wnt3a via beta-catenin were observed for cultured hACs with undersulfation of GAGs (16% of control) and decreased CS content (20% of control). CONCLUSION: This study demonstrates that articular chondrocytes respond to canonical Wnt stimulation, and that reduced sulfation or CS content diminishes that response.


Subject(s)
Cartilage, Articular/metabolism , Chondrocytes/metabolism , Glycosaminoglycans/metabolism , Signal Transduction , Wnt Proteins/physiology , Animals , Cattle , Humans
18.
Orthod Craniofac Res ; 8(3): 200-8, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16022722

ABSTRACT

OBJECTIVES: Cartilage is avascular and relatively homogeneous, making it an attractive tissue for in vitro histogenesis and surgical use in patients. We developed novel platform technologies in order to define the requirements for optimal in vitro chondrogenesis by isolated cells. In this series of studies, we tested alternatives to fetal bovine serum (FBS) and the effects of growth factors on formation of cartilage in 3D porous collagen sponges. DESIGN: We used porous collagen sponges to assess the effects of serum substitutes and exogenous TGF-beta1 and IL-1alpha on chondrocytes (bovine articular chondrocytes, bACs) and on chondroinduced human dermal fibroblasts (hDFs). We determined the effects of low concentrations of FBS and two serum substitutes, Nutridoma and ITS(+3), on cellularity and matrix production. After culture for intervals, sponges were harvested for histological and biochemical measurement of cartilage-specific chondroitin 4-sulfate proteoglycan (C 4-S PG). RESULTS: Cultured bACs showed equivalent growth in Nutridoma (1%) and 10% FBS. Both TGF-beta1 and IL-1alpha significantly stimulated accumulation of C 4-S PG by bACs in 3D porous collagen sponges. Many endogenous growth factors were upregulated in hDFs cultured with chondroinductive DBP. Addition of TGF-beta1 and IL-1alpha for 11 days significantly stimulated accumulation of C 4-S PG by hDFs cultured in DMEM with 1% Nutridoma. CONCLUSION: Porous collagen sponges are supportive of chondrogenesis and of chondroinduction by DBP. Optimization of serum-free culture conditions, including growth factors, matrix components, and mechanical stimuli will expedite translation to wider clinical applications. Use of autogenous dermal fibroblasts pre-cultured with DBP and induced to chondrocytes offers an alternative to autogenous chondrocytes.


Subject(s)
Blood Substitutes/pharmacology , Cartilage/drug effects , Interleukin-1/pharmacology , Tissue Engineering/methods , Transforming Growth Factor beta/pharmacology , Animals , Bone Matrix , Cartilage/physiology , Cattle , Cell Movement/drug effects , Cells, Cultured , Chondrocytes/drug effects , Chondrogenesis/drug effects , Chondroitin Sulfate Proteoglycans/analysis , Chondroitin Sulfates/analysis , Collagen/chemistry , Culture Media , Cytokines/analysis , Extracellular Matrix/drug effects , Fibroblasts/drug effects , Humans , Porosity
19.
J Comb Chem ; 7(1): 85-9, 2005.
Article in English | MEDLINE | ID: mdl-15638485

ABSTRACT

Composition-spread La(1-x)SrxMnO3 thin films were prepared by pulsed laser deposition technique from LaMnO3 and SrMnO3 targets. The films were epitaxial with a continuous variation of the out-of-plane lattice parameter along the direction of composition gradient. Scanning Raman spectroscopy has been employed as a nondestructive tool to characterize the composition-spread films. Raman spectra showed the variation of the structural, Jahn Teller distortions and the presence of coexisting phases at particular compositions that are in agreement with the previous observation on the single-crystal samples. Raman spectra on the continuous composition-spread film also reveal the effect of disorder and strain on the compositions.


Subject(s)
Spectrum Analysis, Raman/methods
20.
Int Immunopharmacol ; 4(14): 1745-55, 2004 Dec 20.
Article in English | MEDLINE | ID: mdl-15531291

ABSTRACT

The clear pulp, also known as inner gel, of Aloe vera L. leaf is widely used in various medical, cosmetic and nutraceutical applications. Many beneficial effects of this plant have been attributed to the polysaccharides present in the pulp. However, discrepancies exist regarding the composition of pulp polysaccharide species and an understanding of pulp structure in relation to its chemical composition has been lacking. Thus, we examined pulp structure, isolated structural components and determined their carbohydrate compositions along with analyzing a partially purified pulp-based product (Acemannan hydrogel) used to make Carrisyn hydrogel wound dressing. Light and electron microscopy showed that the pulp consisted of large clear mesophyll cells with a diameter as large as 1000 microm. These cells were composed of cell walls and cell membranes along with a very limited number of degenerated cellular organelles. No intact cellular organelles were found in mesophyll cells. Following disruption of pulp by homogenization, three components were isolated by sequential centrifugation. They were thin clear sheets, microparticles and a viscous liquid gel, which corresponded to cell wall, degenerated cellular organelles and liquid content of mesophyll cells based on morphological and chemical analysis. These three components accounted for 16.2% (+/-3.8), 0.70% (+/-0) and 83.1% of the pulp on a dry weight basis. The carbohydrate composition of each component was distinct; liquid gel contained mannan, microparticles contained galactose-rich polysaccharide(s) and cell walls contained an unusually high level of galacturonic acid (34%, w/w; Gal A). The same three components were also found in Acemannan Hydrogel with mannan as the predominant component. Thus, different pulp structural components are associated with different polysaccharides and thus may potentially be different functionally. These findings may help lay a basis for further studies and development of better controlled processing methods and applications for this well-accepted medicinal plant.


Subject(s)
Aloe/chemistry , Aloe/ultrastructure , Anthracenes/chemistry , Carbohydrates/chemistry , Cell Wall/chemistry , Cellulose/analysis , Electrophoresis , Microscopy, Electron , Plant Leaves/chemistry , Plant Leaves/ultrastructure , Ultracentrifugation , Uronic Acids/chemistry
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