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Decreased Capacity (decreased + capacity)
Selected AbstractsIn vivo muscle architecture and size of the rectus femoris and vastus lateralis in children and adolescents with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2009NOELLE G MOREAU PHD PT Aim, Our aim was to investigate muscle architecture and size of the rectus femoris (RF) and vastus lateralis (VL) in children and adolescents with cerebral palsy (CP) compared with age-matched typically developing participants. Method, Muscle architecture and size were measured with ultrasound imaging in 18 participants with spastic CP (9 females, 9 males; age range 7.5,19y; mean age 12y [SD 3y 2mo]) within Gross Motor Function Classification System levels I (n=4), II (n=2), III (n=9), and IV (n=3) and 12 typically developing participants (10 females, 2 males; age range 7,20y; mean age 12y 4mo [SD 3y 11mo]). Exclusion criteria were orthopedic surgery or neurosurgery within 6 months before testing or botulinum toxin injections to the quadriceps within 3 months before testing. Results, RF cross-sectional area was significantly lower (48%), RF and VL muscle thickness 30% lower, RF fascicle length 27% lower, and VL fascicle angle 3° less in participants with CP compared to the typically developing participants (p<0.05). Intraclass correlation coefficients were ,0.93 (CP) and , 0.88 (typical development), indicating excellent reliability. Interpretation, These results provide the first evidence of altered muscle architecture and size of the RF and VL in CP, similar to patterns observed with disuse and aging. These alterations may play a significant role in the decreased capacity for force generation as well as decreased shortening velocity and range of motion over which the quadriceps can act. [source] Prognostic value of combination of heart-type fatty acid-binding protein and ischemia-modified albumin in patients with acute coronary syndromes and normal troponin T valuesJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2009Cui Liyan Abstract Recent studies have suggested that heart-type fatty acid-binding protein (H-FABP) may detect ongoing myocardial damage involved in the progression of acute coronary syndromes (ACS). This study was prospectively designed to examine whether the combination of H-FABP, a marker for ongoing myocardial damage, and ischemia-modified albumin (IMA), a marker for myocardial ischemia, would effectively diagnose patients with ACS. H-FABP values above 1.5,µg/l can be correctly measured via an ELISA and 6,µg/l is the currently used cut-off value (1,3). We measured serum H-FABP and IMA of 108 patients on admission within 12,hr after onset of chestpain and normal troponin T. serum samplesfrom ACS group (n=82) had decreased capacity of ACB [64 (61,67),U/ml] compared with non-ACS ischemic chest pain group (n=26) samples [75 (71,78),U/ml] (P<0.05). The combination of IMA and H-FABP usually had better sensitivity [96.3% (92.2,100%)] (P<0.05) and accuracy [92.6 (87.7,97.5%)] (P<0.05) than when individually used. Thus, the combination of H-FABP and IMA measurements after initiation of chest pain may be highly effective for risk stratification in patients with ACS and normal cardiac troponin T. J. Clin. Lab. Anal. 23:14,18, 2009. © 2009 Wiley-Liss, Inc. [source] Sarcopenia is not due to lack of regenerative drive in senescent skeletal muscleAGING CELL, Issue 2 2005Erik Edström Summary Sarcopenia, loss of skeletal muscle mass, is a hallmark of aging commonly attributed to a decreased capacity to maintain muscle tissue in senescence, yet the mechanism behind the muscle wasting remains unresolved. To address these issues we have explored a rodent model of sarcopenia and age-related sensorimotor impairment, allowing us to discriminate between successfully and unsuccessfully aged cohort members. Immunohistochemistry and staining of cell nuclei revealed that senescent muscle has an increased density of cell nuclei, occurrence of aberrant fibers and fibers expressing embryonic myosin. Using real-time PCR we extend the findings of increased myogenic regulatory factor mRNA to show that very high levels are found in unsuccessfully aged cohort members. This pattern is also reflected in the number of embryonic myosin-positive fibers, which increase with the degree of sarcopenia. In addition, we confirm that there is no local down-regulation of IGF-I and IGF-IR mRNA in aged muscle tissue; on the contrary, the most sarcopenic individuals showed significantly higher local expression of IGF-I mRNA. Combined, our results show that the initial drive to regenerate myofibers is most marked in cases with the most advanced loss of muscle mass, a pattern that may have its origin in differences in the rate of tissue deterioration and/or that regenerating myofibers in these cases fail to mature into functional fibers. Importantly, the genetic background is a determinant of the pace of progression of sarcopenia. [source] Catecholamine exocytosis is diminished in R6/2 Huntington's disease model miceJOURNAL OF NEUROCHEMISTRY, Issue 5 2007Michael A. Johnson Abstract In this work, the mechanisms responsible for dopamine (DA) release impairments observed previously in Huntington's disease model R6/2 mice were evaluated. Voltammetrically measured DA release evoked in striatal brain slices from 12-week old R6/2 mice by a single electrical stimulus pulse was only 19% of wild-type (WT) control mice. Iontophoresis experiments suggest that the concentration of released DA is not diluted by a larger striatal extracellular volume arising from brain atrophy, but, rather, that striatal dopaminergic terminals have a decreased capacity for DA release. This decreased capacity was not due to an altered requirement for extracellular Ca2+, and, as in WT mice, the release in R6/2 mice required functioning vesicular transporters. Catecholamine secretion from individual vesicles was measured during exocytosis from adrenal chromaffin cells harvested from R6/2 and WT mice. While the number of exocytotic events was unchanged, the amounts released per vesicle were significantly diminished in R6/2 mice, indicating that vesicular catecholamines are present in decreased amounts. Treatment of chromaffin cells with 3-nitropropionic acid decreased the vesicular release amount from WT cells by 50%, mimicking the release observed from untreated R6/2 cells. Thus, catecholamine release from tissues isolated from R6/2 mice is diminished because of impaired vesicle loading. [source] Intervertebral disc cell response to dynamic compression is age and frequency dependent,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2009Casey L. Korecki Abstract The maintenance of the intervertebral disc extracellular matrix is regulated by mechanical loading, nutrition, and the accumulation of matrix proteins and cytokines that are affected by both aging and degeneration. Evidence suggests that cellular aging may lead to alterations in the quantity and quality of extracellular matrix produced. The aims of this study were to examine the role of loading and maturation (a subset of aging), and the interaction between these two factors in intervertebral disc cell gene expression and biosynthesis in a controlled 3D culture environment. Cells were isolated from young (4,6 months) and mature (18,24 months) bovine caudal annulus fibrosus and nucleus pulposus tissue. Isolated cells were seeded into alginate and dynamically compressed for 7 days at either 0.1, 1, or 3 Hz or maintained as a free-swelling control. After 7 days, DNA and sulfated glycosaminoglycan contents were analyzed along with real time, quantitative reverse transcription-polymerase chain reaction analysis for collagen types I and II, aggrecan, and matrix metalloproteinase-3 gene expression. Results suggest that maturation plays an important role in intervertebral disc homeostasis and influences the cell response to mechanical loading. While isolated intervertebral disc cells responded to mechanical compression in 3D culture, the effect of loading frequency was minimal. Altered cellular phenotype and biosynthesis rates appear to be an attribute of the cell maturation process, potentially independent of changes in cellular microenvironment associated with lost nutrition and disc degeneration. Mature cells may have a decreased capacity to create or retain extracellular matrix components in response to mechanical loading compared to young cells. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 800,806, 2009 [source] Ease and effectiveness of costly autotomy vary with predation intensity among lizard populationsJOURNAL OF ZOOLOGY, Issue 3 2004William E. Cooper Jr Abstract Costly anti-predatory defences are used in ecological time and maintained in evolutionary time by natural selection favouring individuals that survive through their use. Autotomy of expendable body parts is a striking example of a defence having multiple substantial costs, including loss of ability to use the same defence, loss of energy, and decreased growth, reproductive success and survival following autotomy, plus the energetic cost of replacing the lost body part in species capable of regenerating them. Our study shows that autotomy in the lacertid lizard Podarcis lilfordi reduces sprint speed, indicating decreased capacity to escape as well as the loss of energy. Autotomy carries substantial cost, and thus should be avoided except as a last resort. Ease of autotomy and post-autotomic movements were studied in three populations of lacertid lizards. Two were islet populations of P. lilfordi from Aire (lowest predation pressure) and Colom (intermediate predation pressure) off Minorca. The third was a mainland population of Podarcis hispanica, a closely related species from the mainland of the Iberian Peninsula where predation pressure is higher than on the islets. As predicted, a suite of autotomic traits increases the effectiveness of autotomy as a defence as predation pressure increases. With increasing predation pressure, the frequency of voluntary autotomy increases, latency to autotomy decreases, pressure on the tail needed to induce autotomy decreases, vigour of post-autotomic tail movements increases, and distance moved by the shed tail increases. Additional changes that might be related to predation pressure, but could have other causes, are the presence of tail coloration contrasting with body coloration except under the lowest predation pressure (Aire) and longer tails in the mainland species P. hispanica. Correspondence between predation pressure and the suite of autotomic traits suggests that autotomy is an important defence that responds to natural selection. Comparative data are needed to establish the generality of relationships suggested in our study of only three populations. [source] Mutations of genes in synthesis of the carotenoid precursors of ABA lead to pre-harvest sprouting and photo-oxidation in riceTHE PLANT JOURNAL, Issue 2 2008Jun Fang Summary Pre-harvest sprouting (PHS) or vivipary in cereals is an important agronomic trait that results in significant economic loss. A considerable number of mutations that cause PHS have been identified in several species. However, relatively few viviparous mutants in rice (Oryza sativa L.) have been reported. To explore the mechanism of PHS in rice, we carried out an extensive genetic screening and identified 12 PHS mutants (phs). Based on their phenotypes, these phs mutants were classified into three groups. Here we characterize in detail one of these groups, which contains mutations in genes encoding major enzymes of the carotenoid biosynthesis pathway, including phytoene desaturase (OsPDS), ,-carotene desaturase (OsZDS), carotenoid isomerase (OsCRTISO) and lycopene , -cyclase (,-OsLCY), which are essential for the biosynthesis of carotenoid precursors of ABA. As expected, the amount of ABA was reduced in all four phs mutants compared with that in the wild type. Chlorophyll fluorescence analysis revealed the occurrence of photoinhibition in the photosystem and decreased capacity for eliminating excess energy by thermal dissipation. The greatly increased activities of reactive oxygen species (ROS) scavenging enzymes, and reduced photosystem (PS) II core proteins CP43, CP47 and D1 in leaves of the Oscrtiso/phs3-1mutant and OsLCY RNAi transgenic rice indicated that photo-oxidative damage occurred in PS II, consistent with the accumulation of ROS in these plants. These results suggest that the impairment of carotenoid biosynthesis causes photo-oxidation and ABA-deficiency phenotypes, of which the latter is a major factor controlling the PHS trait in rice. [source] Functional Impairment of Renal Organic Cation Transport in Experimental DiabetesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2002Brett Grover The experiments compared the ability of renal cortex slices from streptozotocin-induced diabetic and non-diabetic rats to accumulate the model cation, 14C-tetraethylammonium under controlled conditions. Initial experiments demonstrated a progressive decline in tetraethylammonium accumulation with increasing duration of diabetes. The maximal decrease was observed at 21 days after streptozotocin injection. Time-dependent incubations revealed that tetraethylammonium uptake from both diabetic and non-diabetic rats followed a curvilinear pattern expected of an active process. However, at steady state the diabetic-derived slices accumulated a significant 38% less tetraethylammonium versus slices from non-diabetics. Concentration-dependent incubations of tetraethylammonium (0.01,10 mM, 60 min.) demonstrated saturable transport in both diabetic and non-diabetic slices with a significantly decreased capacity of diabetic-derived slices to accumulate tetraethylammonium. Cellular respiration rates in the two groups were not different. Insulin treatment of the diabetic rats prevented the transport decline. While the causative factor of the transport impairment in diabetes is unresolved, this study documents an aspect of diabetic nephropathy that has not been previously reported but which may have important implications for renal excretion of cationic drugs and toxicants. The results also provide a mechanism for the well-documented "protection phenomenon" by which the kidneys of diabetic rats are resistant to nephrotoxicity induced by the chemotherapeutic agent cisplatin. [source] Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2002M. Aleksza Summary Background A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon-, (IFN-,) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD). Objectives To clarify the results of recent studies concerning the role of interleukin (IL)-4 and IL-13 in PBMCs of AD patients, we analysed the activation status of lymphocyte subpopulations. Methods We measured the intracellular expression and serum levels of certain type 1 and type 2 cytokines, using cell surface and intracellular cytokine staining, flow cytometry and enzyme-linked immunosorbent assay techniques. Results The frequency of IL-10 and IL-13 producing CD4+ and CD8+ T cells was significantly higher in patients with AD, while the frequency of IFN-, secreting helper and cytotoxic T cells was significantly lower in patients with AD than in control subjects. The serum levels of IL-10 and IL-13 were also significantly increased. There were no significant differences observed between the experimental groups in the frequency of IL-4 producing CD4+ and CD8+ cells. Conclusions This study demonstrates a type 2 cytokine production in the CD4+ and CD8+ T cells of AD patients, which is characterized by an elevated IL-13, but not by IL-4 secretion, and by an increased level of the immunoregulatory IL-10, which can contribute to a decrease in IFN-, expression. [source] Impaired host defense to Klebsiella pneumoniae infection in mice treated with the PDE4 inhibitor rolipramBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2003A C Soares The increase in levels of cAMP in leukocytes by selective inhibitors of PDE4 may result in reduction of inflammation, and may be useful in the treatment of pulmonary inflammatory disorders in humans. Here, we have assessed whether oral treatment with the prototype PDE4 inhibitor, rolipram, interfered with the antibacterial host response following pulmonary infection of mice with Klebsiella pneumoniae. K. pneumoniae infection induced a marked increase in the recruitment of neutrophils to the lungs and the production of proinflammatory cytokines and chemokines, including tumor necrosis factor- , (TNF- ,) and keratinocyte-derived chemokine (KC), in bronchoalveolar (BAL) fluid and lung tissue. There were also detectable amounts of interleukin-10 (IL-10) and significant lethality. Treatment with rolipram (3,30 mg kg,1) was associated with earlier lethality and significant inhibition of the TNF- , production. This was associated with enhanced production of IL-10 in lung tissue of rolipram-treated animals. Rolipram treatment did not affect KC expression and the recruitment of neutrophils in the lung tissue. Over 70% of neutrophils that migrated into the BAL fluid following K. pneumoniae infection ingested bacteria. Treatment with rolipram inhibited the percentage of neutrophils undergoing phagocytosis of K. pneumoniae in a dose-dependent manner. Maximal inhibition (62%) occurred at doses equal to or greater than 10 mg kg,1. Thus, treatment of mice with the PDE4 inhibitor rolipram is accompanied by earlier lethality, enhanced bacterial load and decreased capacity of the responding host to produce TNF- , and of neutrophils to phagocytose bacteria. It will be important to investigate whether the shown ability of PDE4 inhibitors to inhibit neutrophil phagocytosis and control experimental bacterial infection will translate into an inhibition of the ability of neutrophils to deal with infectious microorganisms in the clinical setting. British Journal of Pharmacology (2003) 140, 855,862. doi:10.1038/sj.bjp.0705517 [source] The Plasmodium TRAP/MIC2 family member, TRAP-Like Protein (TLP), is involved in tissue traversal by sporozoitesCELLULAR MICROBIOLOGY, Issue 7 2008Cristina K. Moreira Summary In the apicomplexan protozoans motility and cell invasion are mediated by the TRAP/MIC2 family of transmembrane proteins, members of which link extracellular adhesion to the intracellular actomyosin motor complex. Here we characterize a new member of the TRAP/MIC2 family, named TRAP- Like Protein (TLP), that is highly conserved within the Plasmodium genus. Similar to the Plasmodium sporozoite protein, TRAP, and the ookinete protein, CTRP, TLP possesses an extracellular domain architecture that is comprised of von Willebrand factor A (vWA) and thrombospondin type 1 (TSP1) domains, plus a short cytoplasmic domain. Comparison of the vWA domain of TLP genes from multiple Plasmodium falciparum isolates showed relative low sequence diversity, suggesting that the protein is not under selective pressures of the host immune system. Analysis of transcript levels by quantitative reverse transcription polymerase chain reaction (RT-PCR) showed that TLP is predominantly expressed in salivary gland sporozoites of P. falciparum and P. berghei. Targeted disruption of P. berghei TLP resulted in a decreased capacity for cell traversal by sporozoites, and reduced infectivity of sporozoites in vivo, whereas in vitro sporozoite motility and hepatocyte invasion were unaffected. These results indicate a role of TLP in cell traversal by sporozoites. [source] Comparative therapeutic effects of orally administered 1,25-dihydroxyvitamin D3 and 1alpha-hydroxyvitamin D3 on type-1 diabetes in non-obese diabetic mice fed a normal-calcaemic dietCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2008J. P. Driver Summary Frequent injections of the hormonal form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25D3) reportedly inhibits autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by correcting some of the abnormalities in antigen-presenting cells which contribute the development of pathogenic T cell responses. This route of administration greatly elevates the levels of these compounds in the bloodstream for hours after treatment, which requires mice to be fed diets formulated to contain much reduced levels of Ca to avoid the toxic effects of hypercalcaemia. In the current work, we demonstrate that feeding 1,25D3 or its synthetic precursor, 1alpha(OH) vitamin D3 (1alphaD3), as part of a T1D supportive chow diet containing normal levels of Ca, is an effective means of reducing the incidence of disease in NOD mice, but the doses required for protection elicited hypercalcaemia. However, T1D protection elicited by D3 analogue feeding appears, at least partially, to have an immunological basis, as splenic T cells from treated mice had a decreased capacity to adoptively transfer disease. Protection is associated with an increased proportion of T cells with CD4+ forkhead box P3+ regulatory phenotype within the islet infiltrate of treated animals. The 1alphaD3 precursor is converted rapidly to the active 1,25D3 isoform in vivo. However, feeding the 1alphaD3 analogue elicited stronger T1D protection than the 1,25D3 compound, but also induced more severe hypercalcaemia. In future, the dietary supplementation of novel low-calcaemic D3 analogues may enable their continuous delivery at levels that inhibit T1D development in susceptible humans consuming normal levels of Ca. [source] | |||||||||||||