Summary
We propose that the measurement of the bone mineral density (BMD) of the proximal humerus be standardized using the dual energy X-ray absorptiometry (DXA) in patients supposed to undergo ...rotator cuff repair surgery as well as those with the fracture of the proximal humerus as the BMD of the proximal humerus is decreased in these patients.
Introduction
We propose that the measurement of the BMD of the proximal humerus be standardized using the DXA in patients who are supposed to undergo rotator cuff repair surgery as well as those with the fracture of the proximal humerus.
Methods
We conducted the prospective study in 213 patients with unilateral rotator cuff tear but without contralateral shoulder pain or disease. In these patients, we preoperatively measured the BMD of the bilateral proximal humeri with a repeat measurement in 20 patients. We predefined three regions of interest (ROIs) in the proximal humerus with the consideration of the rotator cuff repair surgery as well as proximal humeral fractures.
Results
The measurement of the BMD of the proximal humerus using the DXA showed excellent reliability (intraclass correlation coefficient > .90). BMD values of all three ROIs in the affected shoulder were significantly lower than those in asymptomatic shoulder (all
p
< 0.05). In female patients, the BMD values of ROIs in bilateral shoulder were significantly lower than those in male patients (all
p
< 0.001). In multiple regressions, however, there were no significant correlations between other clinical characteristics, except for the gender, and the BMD of GT in the affected shoulder.
Conclusions
It is imperative that the bone quality of the proximal humerus be accurately evaluated prior to surgery in patients who are supposed to undergo rotator cuff repair using suture anchors as well as in those with proximal humeral fractures. This is because the BMD of the proximal humerus is decreased in these patients.
Among 5938 clinical Shigella spp. isolates, two S. flexneri strains were isolated as those resistant to fluoroquinolones based on the MICs of the following antibiotics: ciprofloxacin, norfloxacin, ...ofloxacin, sparfloxacin and levofloxacin. S. flexneri 021787 had three substitutions, one in GyrA (Ser83Leu) and two in ParC (Ser80Ile and Arg91Gln). S. flexneri 021895 had four substitutions, two in GyrA (Ser83Leu and Asp87Gly) and two in ParC (Ser80Ile and Arg91Gln). The increased susceptibility of S. flexneri 021787 and S. flexneri 021895 to ciprofloxacin, norfloxacin and ofloxacin in the presence of the uncoupler carbonyl cyamide-m-chlorophenyldrazone implied that energy-dependent active efflux pumps contributed to the resistance against fluoroquinolones. Both S. flexneri 021787 and S. flexneri 021895 were also induced to express tolC (encoding a resistance–nodulation–division transporter), mdfA (encoding a major facilitator superfamily transporter), and ydhE (encoding a multidrug and toxic compound extrusion transporter) in the presence of ciprofloxacin. Thus, these results indicated that chromosome-mediated fluoroquinolone resistance of S. flexneri 021787 and S. flexneri 021895 resulted from the combination of target site mutations and enhanced expression of genes encoding efflux pumps.
The collapse of the magnetic exchange splitting in 7 monolayer thick epitaxial Ni/W(110) films following a femtosecond laser pulse was measured using time-resolved photoemission spectroscopy. ...Ultrafast demagnetization during the laser induced hot electron cascade proceeds via spin-flip excitations with a relaxation time constant of 300+/-70 fs. At longer times the electronic system cools down and the magnetization is finally reestablished with a time constant of 3.2+/-0.2 ps.
Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is suspected to be one of the anti-oxidant enzymes and virulence determinants active in some pathogenic micro-organisms. To elucidate the ...role of Cu/ZnSOD in the major human fungal pathogen Candida albicans, its gene, designated SOD1, was disrupted by the URA-blaster technique. The resulting sod1/sod1 mutant showed delayed hyphal growth on Spider medium but could still form hyphae on other solid media or in liquid media, particularly in response to serum. Moreover, the sod1/sod1 mutant was more sensitive to menadione, a redox-cycling agent, than the isogenic wild-type strain, although it still showed an adaptive oxidative stress response. Furthermore, the sod1/sod1 mutant cells exhibited slow growth in minimal medium when compared to the wild-type cells, but their growth was restored by the addition of lysine to the medium. Interestingly, C. albicans cells lacking Cu/ZnSOD showed increased susceptibility to macrophage attack and had attenuated virulence in mice. Thus, these results suggest that Cu/ZnSOD is required for the protection of C. albicans against oxidative stresses and for the full virulence of the organism to be expressed.
Glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (EX) have been considered as a growth factor implicated in pancreatic islet mass increase and β-cell proliferation. This study aimed to ...investigate the effect of EX on cyclin D1 expression, a key regulator of the cell cycle, in the pancreatic β-cell line INS-1. We demonstrated that EX significantly increased cyclin D1 mRNA and subsequently its protein levels. Although EX induced phosphorylation of Raf-1 and extracellular-signal-regulated kinase (ERK), both PD98059 and exogenous ERK1 had no effect on the cyclin D1 induction by EX. Instead, the cAMP-elevating agent forskolin induced cyclin D1 expression remarkably and this response was inhibited by pretreatment with H-89, a protein kinase A (PKA) inhibitor. Promoter analyses revealed that the cAMP-responsive element (CRE) site (at position −48; 5′-TAACGTCA-3′) of cyclin D1 gene was required for both basal and EX-induced activation of the cyclin D1 promoter, which was confirmed by site-directed mutagenesis study. For EX to activate the cyclin D1 promoter effectively, CRE-binding protein (CREB) should be phosphorylated and bound to the putative CRE site, according to the results of electrophoretic mobility shift and chromatin immunoprecipitation assays. Lastly, a transfection assay employing constitutively active or dominant-negative CREB expression plasmids clearly demonstrated that CREB was largely involved in both basal and EX-induced cyclin D1 promoter activities. Taken together, EX-induced cyclin D1 expression is largely dependent on the cAMP/PKA signaling pathway, and EX increases the level of phosphorylated CREB and more potently trans-activates cyclin D1 gene through binding of the CREB to the putative CRE site, implicating a potential mechanism underlying β-cell proliferation by EX.
Abstract In recent years, research in the areas of stem cells has dramatically increased, including studies of cellular adhesion to a substrate. We sought to determine the adhesive properties of ...human adipose-derived stem cells (hASCs) for extracellular matrix proteins. The adhesion of hASCs to collagens and laminin was completely inhibited by a monoclonal antibody, Mab 2253, which binds to the β1 integrin subunit. These data indicate that hASC adhesion to collagens and laminin was exclusively mediated by an integrin. Cell adhesion on fibronectin (Fn) was inhibited by the heparin-binding peptide (HBP) in the presence of Mab 2253, but not by either Mab 2253 or HBP alone. These results indicate that both the β1 subunit and the heparan sulfate proteoglycan participated in the cell adhesion to Fn. Microscopic views showed extensive spreading of hASCs cultured on Fn, whereas the cells maintained a round shape when cultured on a heparin-binding domain (HBD) substrate. hASCs differentiated into adipocytes, which stained positive for lipid vacuoles by Oil Red-O analysis, more readily on HBD substrate than on FN substrate. These results suggest that hASCs have an adhesion mechanism for the HBD of Fn and hASC morphology is controlled by the adhesion mechanism and strongly correlated with adipogenic differentiation.
The aim of this study was to investigate the effect of exendin-4 on the expression of cyclin D1 gene (Ccnd1), which is critical in regulating the progression of the cell cycle in INS-1 cells.
INS-1 ...cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assays were performed to measure promoter activities of rat Ccnd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays were used to examine the binding of transcription factors to sites responsive to exendin-4 in vitro and in vivo, respectively.
Exendin-4 increased both Ccnd1 mRNA and its protein levels in a time-dependent manner. The region from -174 to +130 of the promoter was found to contain cis-regulatory elements responsible for exendin-4-mediated gene induction. Early growth response-1 (EGR1) protein was bound to the region from -153 to -134, which includes the putative EGR1 binding site (5'-CACCCCCGC-3'). Moreover, exendin-4 recruited EGR1 protein to the promoter in vivo.
These findings suggest that exendin-4 activates Ccnd1 transcription through induction of EGR1 binding to a cis-regulatory element between -153 and -134 on the rat Ccnd1 promoter. These results provide an important indication that exendin-4 is a growth factor regulating beta cell proliferation.
Objectives
Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether ...complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI.
Materials and methods
Clinical evaluation, comprehensive neuropsychological test, and 18F‐fluoro‐2‐deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24‐month follow‐up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed.
Results
All participants stayed in SMI all the way till the follow‐up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z‐score: −0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (β = 0.43, P = 0.02).
Conclusions
Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time.
The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K
+ channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp technique. Riluzole reversibly inhibited Kv1.5 ...currents in a concentration-dependent manner with an IC
50 of 39.69±2.37μM. G-protein inhibitors (pertussis toxin and GDPβS) did not prevent this inhibition of riluzole on Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage range in which channels are fully activated. Riluzole shifted the steady-state inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration-dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a concentration dependent-manner, but had no effect on the steady-state activation curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of riluzole on Kv3.1, the
Shaw-type K
+ channel were also examined. Riluzole caused a concentration-dependent inhibition of Kv3.1 currents with an IC
50 of 120.98±9.74μM and also shifted the steady-state inactivation curve of Kv3.1 in the hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel.
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