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PubMed1982

Mobility of cytoplasmic and membrane-associated actin in living cells.

We have combined fluorescent analogue cytochemistry with fluorescence photobleaching recovery to measure the mobility of fluorescently labeled actin and other labeled test proteins microinjected into living amoebae. Bovine serum albumin, ovalbumin, and ribonuclease A have a cytoplasmic mobility, expressed as a diffusion coefficient, that is 1/2 to 1/3 of that observed in aqueous solution; 90% of the actin has a mobility 1/2 to 1/8 of that of G-actin in aqueous solution, and approximately equal to 10% of the actin has a mobility comparable to that of F-actin in aqueous solution. Therefore, no more than 10% of the actin in the cytoplasm of amoebae can exist as static filaments. Microinjection of phalloidin decreases the diffusion coefficient of the mobile component of cytoplasmic actin, and it also increases the low-mobility fraction to 50% but has no effect on the mobility of labeled ovalbumin. By comparing the mobility of actin in different parts of amoebae and by separating cytoplasm from plasmalemma-ectoplasm, we found the low-mobility fraction of actin to be enriched in the tail, along the plasmalemma-ectoplasm, and in contracted cytoplasm.

Actins↗

PubMed2006

The relationship between intranuclear mobility of the NF-kappaB subunit p65 and its DNA binding affinity.

It has been hypothesized that the main determinant of the intranuclear mobility of transcription factors is their ability to bind DNA. In the present study, we have extensively tested the relationship between the intranuclear mobility of the NF-kappaB subunit p65 and binding to its consensus target sequence. The affinity of p65 for this binding site is altered by mutation of specific acetylation sites, so these mutants provide a model system to study the relationship between specific DNA binding affinity and intranuclear mobility. DNA binding affinity was measured in vitro using an enzyme-linked immunosorbent assay-based method, and intranuclear mobility was measured using the fluorescence recovery after photobleaching technique on yellow fluorescent protein-tagged p65 constructs. A negative correlation was observed between DNA binding affinity and intranuclear mobility of p65 acetylation site mutants. However, moving the yellow fluorescent protein tag from the C terminus of p65 to the N terminus resulted in an increased mobility but did not significantly affect DNA binding affinity. Thus, all changes in DNA binding affinity produce alterations in mobility, but not vice versa. Finally, a positive correlation was observed between mobility and the randomness of the intranuclear distribution of p65. Our data are in line with a model in which the intranuclear mobility and distribution of a transcription factor are determined by its affinity for specific DNA sequences, which may be altered by protein-protein interactions.

Acetylation↗

PubMed2005

Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist.

Improving approaches for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is clinically important because increased numbers of these cells are needed for enhanced transplantation. Chemokine stromal cell derived factor-1 (also known as CXCL12) is believed to be involved in retention of HSCs and HPCs in bone marrow. AMD3100, a selective antagonist of CXCL12 that binds to its receptor, CXCR4, was evaluated in murine and human systems for mobilizing capacity, alone and in combination with granulocyte colony-stimulating factor (G-CSF). AMD3100 induced rapid mobilization of mouse and human HPCs and synergistically augmented G-CSF-induced mobilization of HPCs. AMD3100 also mobilized murine long-term repopulating (LTR) cells that engrafted primary and secondary lethally-irradiated mice, and human CD34(+) cells that can repopulate nonobese diabetic-severe combined immunodeficiency (SCID) mice. AMD3100 synergized with G-CSF to mobilize murine LTR cells and human SCID repopulating cells (SRCs). Human CD34(+) cells isolated after treatment with G-CSF plus AMD3100 expressed a phenotype that was characteristic of highly engrafting mouse HSCs. Synergy of AMD3100 and G-CSF in mobilization was due to enhanced numbers and perhaps other characteristics of the mobilized cells. These results support the hypothesis that the CXCL12-CXCR4 axis is involved in marrow retention of HSCs and HPCs, and demonstrate the clinical potential of AMD3100 for HSC mobilization.

Animals↗

PubMed2003

Identifying a cut-off point for normal mobility: a comparison of the timed 'up and go' test in community-dwelling and institutionalised elderly women.

BACKGROUND: physical mobility testing is an essential component of the geriatric assessment. The timed up and go test measures basic mobility skills including a sequence of functional manoeuvres used in everyday life. OBJECTIVES: to create a practical cut-off value to indicate normal versus below normal timed up and go test performance by comparing test performance of community-dwelling and institutionalised elderly women. SETTING AND PARTICIPANTS: 413 community-dwelling and 78 institutionalised mobile elderly women (age range 65-85 years) were enrolled in a cross-sectional study. MEASUREMENTS: timed up and go test duration, residential and mobility status, age, height, weight and body mass index were documented. RESULTS: 92% of community-dwelling elderly women performed the timed up and go test in less than 12 seconds and all community-dwelling women had times below 20 seconds. In contrast only 9% of institutionalised elderly women performed the timed up and go test in less than 12 seconds, 42% were below 20 seconds, 32% had results between 20 and 30 seconds and 26% were above 30 seconds. The 10(th)-90(th) percentiles for timed up and go test performance were 6.0-11.2 seconds for community-dwelling and 12.7-50.1 seconds for institutionalised elderly women. When stratifying participants according to mobility status, the timed up and go test duration increased significantly with decreasing mobility (Kruskall-Wallis-test: p<0.0001). Linear regression modelling identified residential status (p<0.0001) and physical mobility status (p<0.0001) as significant predictors of timed up and go performance. This model predicted 54% of total variation of timed up and go test performance. CONCLUSION: residential and mobility status were identified as the strongest predictors of timed up and go test performance. We recommend the timed up and go test as a screening tool to determine whether an in-depth mobility assessment and early intervention, such as prescription of a walking aid, home visit or physiotherapy, is necessary. Community-dwelling elderly women between 65 and 85 years of age should be able to perform the timed up and go test in 12 seconds or less.

Aged↗

PubMed2005

Our "increasingly mobile society"? The curious persistence of a false belief.

PURPOSE: We call attention to the widespread belief that the United States is an "increasingly mobile society," despite the fact that overall mobility has generally declined since about 1950, and interstate mobility has generally not increased during the same period. We review and extend past research documenting these mobility trends. DESIGN AND METHODS: We describe population-level mobility for people of all ages as well as for several adult age groups, using published data from the U.S. Current Population Survey. We use simple regression methods to estimate the size and significance of mobility trends. RESULTS: Overall mobility rates have declined for individuals of all ages and among all age groups. The largest average annual declines occur for 20- to 29-year-olds, although the rate of decline for those aged 65 and older is also large. Interstate mobility has declined slightly or remained constant, except among adults between 45 and 64 years old. IMPLICATIONS: Although there may be good reasons to worry about the future of family care provided to elderly individuals, increased geographic mobility does not appear to be one of them. We speculate on reasons why the false belief persists.

Adult↗

PubMed2000

Mobility problems and perceptions of disability by self-respondents and proxy respondents.

BACKGROUND: The Americans With Disabilities Act defines disability on the basis of physical or mental impairments or external perceptions of impairment. OBJECTIVES: The objective of this study was to examine perceptions of disability among people with lower-extremity mobility difficulties. RESEARCH DESIGN: This study used a cross-sectional, nationally representative survey, the 1994 to 1995 National Health Interview Survey-Disability (NHIS-D) supplement. Using SAS-callable SUDAAN for all analyses, we produced national population estimates. SUBJECTS: This study included 142,572 noninstitutionalized, civilian residents of the United States who were > or =18 years of age, with 80,423 self-respondents and 49,883 proxy respondents. MEASURES: We created a 4-level mobility variable using NHIS-D questions about the ability to walk, climb stairs, stand and the use of mobility aids. We examined associations between mobility and answers to 2 questions about self- and external perceptions of disability. RESULTS: The results showed that 3.1% (estimated 5.82 million persons) reported major mobility difficulties, including 3.7% of self-respondents and 2.7% of those with proxy respondents. Among persons with major mobility problems, 70.8% perceived themselves as disabled, whereas 64.8% thought other people see them as disabled. Also, 80.5% of manual wheelchair users saw themselves as disabled. Proxies were somewhat more likely to perceive disability than self-respondents, although differences were not generally statistically significant. In multivariable regressions, mobility level was the strongest predictor of self-perceived disability, followed by general health status. CONCLUSIONS: Mobility problems increase the likelihood that people will see themselves as disabled, but these perceptions are not universal. Although the schematic of wheelchair users has become an international symbol of disability, many people with serious mobility problems do not view themselves as disabled.

Adult↗

PubMed2005

Mobile-bearing total knee arthroplasty: do the polyethylene bearings rotate?

In vivo kinematics were determined during a weightbearing deep knee bend in 39 patients implanted with four different designs of mobile-bearing total knee arthroplasty to assess polyethylene bearing mobility patterns and magnitudes. The femoral and tibial components and mobile polyethylene insert (implanted with four tantalum beads) were overlaid onto the fluoroscopic images using a three-dimensional model-fitting technique to determine bearing mobility. Three of the four designs were tested at a single time interval while one was evaluated at two postoperative intervals, (12 months apart) to assess changes in bearing mobility with time. All patients had polyethylene bearing rotation relative to the tibial tray and minimal rotation relative to the femoral component. The average maximum amounts of bearing rotation ranged from 8.4 degrees to 10.3 degrees (range, 3.0 degrees -20.1 degrees). In patients evaluated at two time intervals, the average maximum bearing rotation increased from 8.5 degrees (range, 3.4 degrees -15.5 degrees) at 3 months to 9.8 degrees (range, 48 degrees -14.1 degrees) 15 months postoperatively. The presented data demonstrates polyethylene bearing mobility occurs following mobile-bearing total knee arthroplasty and mobility is maintained during the time interval tested. The presence of bearing mobility should result in lower contact stresses reducing the potential for polyethylene wear.

Biomechanical Phenomena↗

PubMed2006

The role of high mobility group box-1 protein in severe sepsis.

PURPOSE OF REVIEW: Despite medical advances, mortality in severe sepsis remains high. As our understanding of the innate immune system has expanded, clinical trials have focused on inhibiting cytokines present early in the infectious process such as interleukin-1 and tumor necrosis factor-alpha, although with disappointing results. There is evidence that the nuclear protein high mobility group box-1 protein, when released extracellularly, acts as a persistent mediator of sepsis and is therefore a promising candidate for therapeutic intervention. This review summarizes current knowledge of the protein and highlights recent relevant findings. RECENT FINDINGS: High mobility group box-1 protein may be released into the circulation either due to necrosis of cells or by active release from macrophages and endothelial cells. Models of experimental sepsis in mice have shown a strong association between extracellular high mobility group box-1 protein and lethality. Treatments against the biological activities of high mobility group box-1 protein reduce lethality in these models. Other studies have shown high mobility group box-1 protein as a key regulator in acute and chronic inflammation. Recent findings confirm that high mobility group box-1 protein is persistently elevated in human patients with severe sepsis. SUMMARY: Despite all efforts, mortality in severe sepsis remains high. A massive amount of evidence indicates high mobility group box-1 protein as a delayed and important propagator of inflammation. Recent studies confirm persisting high levels of high mobility group box-1 protein in serum up to 1 week after hospitalization. Reducing levels of the protein by anti-high mobility group box-1 protein treatment may be one way to moderate uncontrolled inflammation seen in sepsis.

Animals↗

PubMed2006

Latent mobility of osteoporotic vertebral compression fractures.

PURPOSE: To describe the property of latent mobility in osteoporotic vertebral compression fractures (VCFs) and discuss its clinical significance. MATERIALS AND METHODS: This was a retrospective case series of 14 patients with 14 painful osteoporotic VCFs who were comfortably confined to the supine position overnight for the purpose of vertebral height restoration. There was sufficient additional vertebral height restoration the following morning to allow percutaneous vertebroplasty (PV) in some patients when this had initially been deemed unsafe or technically impossible. Anterior vertebral height of the index VCF was measured from the preoperative standing lateral, immediate cross-table supine lateral, and postconfinement cross-table supine lateral radiographs as well as the first postoperative standing lateral radiograph. Dynamic mobility was defined as the difference in anterior vertebral height between preoperative standing lateral and immediate cross-table supine lateral radiographs. Latent mobility was defined as difference in anterior vertebral height between immediate cross-table supine lateral and postconfinement cross-table supine lateral radiographs. Postoperative vertebral height restoration was defined as the difference in anterior vertebral height between preoperative and first postoperative standing lateral radiographs. Mean patient age was 81.0 years, and mean fracture age was 83.6 days. RESULTS: Dynamic mobility averaged +4.7 mm (range, -2.1 to +12.6 mm; P = .001). Latent mobility averaged +2.7 mm (range, -1.9 to +15.5; P < .02). The average sum of preoperative dynamic and latent mobility (+7.4 mm; range -1.0 to +17.0; P < .001) was not different from final postoperative vertebral height restoration (P > .4). PV was successfully accomplished in all cases. CONCLUSIONS: Latent mobility occurs in some VCFs and contributes to vertebral height restoration. Recognition of latent mobility may permit vertebroplasty in some patients in whom the procedure had otherwise been deemed unsafe. Reports of vertebral height restoration following vertebral augmentation should account for that proportion resulting from dynamic and latent mobility.

Aged↗

PubMed1984

Proteus mirabilis chromosome mobilization by plasmid D: a physical characterization.

Plasmid D, a hybrid of plasmids P-lac and R1 drd19, mediates polarized chromosome mobilization from one origin in Proteus mirabilis strain PM5006, while the parental plasmids neither individually nor combined mobilize this chromosome. To elucidate its acquired mobilizing ability plasmid D was characterized physically in relation to P-lac and R1 drd19. Restriction patterns of these plasmids were compared and it was shown that D consists of P-lac and only the r-determinant (r-det) of R1 drd19. A mechanism for the formation of plasmid D, via transduction of the r-det and subsequent transposon-like integration into P-lac, involving insertion sequence IS1, was suggested. Evidence for aberration in plasmid D DNA as a result of r-det integration into P-lac was attributed to IS1 elements which flank the r-det. Recombination regions of parental plasmid DNA were located on HindIII fragments alpha and beta of plasmid D and were subsequently inserted in vitro into IncP-1 plasmid RP4 that fails to mobilize the P. mirabilis chromosome. RP4::HindIII alpha plasmids did not mobilize the latter chromosome, but rendered the Proteus host lac+. RP4::HindIII beta plasmids pMC1 and pMC17, containing the fragment in opposite orientations, mobilized the P. mirabilis chromsome. For pMC17, mobilization was indistinguishable from that of plasmid D, i.e. having the same orientation and the same single origin. However, mobilization promoted by pMC1 was from two distinctly different origins, different from that of pMC17. This apparently deviates from known examples where inversion of homologous DNA inserted into plasmids leads to mobilization from the same origin but in reverse direction.

Chromosome Mapping↗

PubMed2005

Using mobile technologies to give health students access to learning resources in the UK community setting.

OBJECTIVES: This article describes a project which explored the potential for mobile technologies to give health students in the community access to learning resources. The purpose included the need to identify possible barriers students could face in using mobile technologies. Another focus was to assess the students perceptions of the importance of being able to access learning resources in the community. METHODS: This 1-year project used two main approaches for data collection. A review of the literature on mobile technologies in the health context was conducted. This was used in a systematic way to identify key issues and trends. The literature review was used to inform the design and production of a questionnaire. This was distributed to and completed by a group of community health students at Northumbria University, UK. The questionnaire was piloted and there was a 100% completion rate with 49 returned forms. RESULTS: The literature review indicated that most mobile technology applications were occurring in the US. At the time of the review the most prevalent mobile technologies were PDAs, laptops, WAP phones and portable radios with use being concentrated around doctors in the acute sector. A range of advantages and disadvantages to the technology were discovered. Mobile technologies were mainly being used for clinical rather than learning applications. The students showed a low level of awareness of the technology but placed great importance to accessing learning resources from the community. CONCLUSIONS: Significant development and changes are taking place in mobile technologies. Since the data collection for this work was completed in 2004 podcasting and videocasting have become significant in mobile learning for health professionals. Librarians will need to address the relevance and implications of m-learning for their practice. Care and consideration needs to be given on the time and resources librarians allocate for the necessary development work around mobile technologies. Collaboration and partnership working will be most effective approach for librarians wishing to integrate their services with m-learning technologies.

Computer Communication Networks↗

PubMed1989

Stimulation by ATP of inositol trisphosphate accumulation and calcium mobilization in cultured adrenal chromaffin cells.

Effects of ATP on accumulation of inositol phosphates and Ca2+ mobilization were investigated in cultured bovine adrenal chromaffin cells. When the cells were stimulated with 30 microM ATP, a rapid and transient rise in intracellular Ca2+ concentration was observed. At the same time, ATP rapidly increased accumulation of inositol phosphates. The concentration-response curve for the ATP-induced Ca2+ mobilization was similar to that for inositol trisphosphate (IP3) accumulation. ATP exerted its maximal effects at 30 microM for either IP3 accumulation or Ca2+ mobilization. The order of the efficacy of the agonists for IP3 accumulation and Ca2+ mobilization at 100 microM was ATP greater than ADP greater than AMP approximately adenosine, AMP (100 microM) and adenosine (300 microM) failed to induce IP3 accumulation and Ca2+ mobilization. Although 100 microM GTP and 100 microM UTP also induced IP3 accumulation and Ca2+ mobilization, their efficacy was less than that of ATP. CTP (100 microM) induced a slight IP3 accumulation, but it did not induce Ca2+ mobilization. Nifedipine (10 microM), a Ca2+ channel antagonist, and theophylline (100 microM), a P1-purinergic receptor antagonist, failed to inhibit the ATP-induced IP3 accumulation and Ca2+ mobilization. The above two cellular responses induced by ATP were also observed in the Ca2+-depleted medium. ATP induced a rapid and transient accumulation of 1,4,5-IP3 (5s), followed by a slower accumulation of 1,3,4-IP3. These results suggest that ATP induces the formation of 1,4,5-IP3 through the P2-purinergic receptor and consequently promotes Ca2+ mobilization from intracellular storage sites in cultured adrenal chromaffin cells.

Adenosine Diphosphate↗

PubMed2004

Inflammatory markers and incident mobility limitation in the elderly.

OBJECTIVES: To examine the relationship between indicators of inflammation and the incidence of mobility limitation in older persons. DESIGN: Prospective cohort study: the Health, Aging and Body Composition Study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: A total of 2,979 men and women, aged 70 to 79, without mobility limitation at baseline. MEASUREMENTS: Serum levels of interleukin (IL)-6, tumor necrosis factor alpha (TNFalpha), and C-reactive protein (CRP) and soluble cytokine receptors (IL-2sR, IL-6sR, TNFsR1, TNFsR2) were measured. Mobility limitation was assessed and defined as reporting difficulty or inability to walk one-quarter of a mile or to climb 10 steps during two consecutive semiannual assessments over 30 months. RESULTS: Of the 2,979 participants, 30.1% developed incident mobility limitation. After adjustment for confounders (demographics, prevalent conditions at baseline, body composition), the relative risk (RR) of incident mobility limitation per standard deviation (SD) increase was 1.19 (95% confidence interval (CI)=1.10-1.28) for IL-6, 1.20 (95% CI=1.12-1.29) for TNFalpha, and 1.40 (95% CI=1.18-1.68) for CRP. The association between inflammation and incident mobility limitation was especially strong for the onset of more severe mobility limitation and when the levels of multiple inflammatory markers were high. When persons with baseline or incident cardiovascular disease events or persons who were hospitalized during study follow-up were excluded, findings remained similar. In a subset (n=499), high levels of the soluble receptors IL2sR and TNFsR1 (per SD increase: RR=1.23 (95% CI=1.04-1.46) and RR=1.28 (95% CI=1.04-1.57), respectively) were also associated with incident mobility limitation. CONCLUSION: Findings suggest that inflammation is prognostic for incident mobility limitation over 30 months, independent of cardiovascular disease events and incident severe illness.

Aged↗

PubMed2005

Relationship between intracellular pH and proton mobility in rat and guinea-pig ventricular myocytes.

Intracellular H+ ion mobility in eukaryotic cells is low because of intracellular buffering. We have investigated whether Hi+ mobility varies with pHi. A dual microperfusion apparatus was used to expose guinea-pig or rat myocytes to small localized doses (3-5 mm) of ammonium chloride (applied in Hepes-buffered solution). Intracellular pH (pHi) was monitored confocally using the fluorescent dye, carboxy-SNARF-1. Local ammonium exposure produced a stable, longitudinal pHi gradient. Its size was fed into a look-up table (LUT) to give an estimate of the apparent intracellular proton diffusion coefficient (D(app)H). LUTs were generated using a diffusion-reaction model of Hi+ mobility based on intracellular buffer diffusion. To examine the pHi sensitivity of D(app)H, whole-cell pHi was initially displaced using a whole-cell ammonium or acetate prepulse, before locally applying the low dose of ammonium. In both rat and guinea-pig, D(app)H decreased with pHi over the range 7.5-6.5. In separate pipette-loading experiments, the intracellular diffusion coefficient for carboxy-SNARF-1 (a mobile-buffer analogue) exhibited no significant pHi dependence. The pHi sensitivity of D(app)H is thus likely to be governed by the mobile fraction of intrinsic buffering capacity. These results reinforce the buffer hypothesis of Hi+ mobility. The pHi dependence of D(app)H was used to characterize the mobile and fixed buffer components, and to estimate D(mob) (the average diffusion coefficient for intracellular mobile buffer). One consequence of a decline in Hi+ mobility at low pHi is that it will predispose the myocardium to pHi nonuniformity. The physiological relevance of this is discussed.

Animals↗

PubMed2006

Mobility of human immunodeficiency virus type 1 Pr55Gag in living cells.

Human immunodeficiency virus type 1 (HIV-1) assembly requires the converging of thousands of structural proteins on cellular membranes to form a tightly packed immature virion. The Gag polyprotein contains all of the determinants important for viral assembly and must move around in the cell in order to form particles. This work has focused on Gag mobility in order to provide more insights into the dynamics of particle assembly. Key to these studies was the use of several fluorescently labeled Gag derivatives. We used fluorescence recovery after photobleaching as well as photoactivation to determine Gag mobility. Upon expression, Gag can be localized diffusely in the cytoplasm, associated with the plasma membrane, or in virus-like particles (VLPs). Here we show that Gag VLPs are primarily localized in the plasma membrane and do not colocalize with CD63. We have shown using full-length Gag as well as truncation mutants fused to green fluorescent protein that Gag is highly mobile in live cells when it is not assembled into VLPs. Results also showed that this mobility is highly dependent upon cholesterol. When cholesterol is depleted from cells expressing Gag, mobility is significantly decreased. Once cholesterol was replenished, Gag mobility returned to wild-type levels. Taken together, results from these mobility studies suggest that Gag is highly mobile and that as the assembly process proceeds, mobility decreases. These studies also suggest that Gag assembly must occur in cholesterol-rich domains in the plasma membrane.

Animals↗

PubMed2003

Molecular determinants of glucocorticoid receptor mobility in living cells: the importance of ligand affinity.

The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which is activated upon ligand binding, and can alter the expression of target genes either by transrepression or transactivation. We have applied FRAP (fluorescence recovery after photobleaching) to quantitatively assess the mobility of the yellow fluorescent protein (YFP)-tagged human GR alpha-isoform (hGRalpha) in the nucleus of transiently transfected COS-1 cells and to elucidate determinants of its mobility. Addition of the high-affinity agonist dexamethasone markedly decreases the mobility of the receptor in a concentration-dependent manner, whereas low-affinity ligands like corticosterone decrease the mobility to a much lesser extent. Analysis of other hGRalpha ligands differing in affinity suggests that it is the affinity of the ligand that is a major determinant of the decrease in mobility. Similar results were observed for two hGRalpha antagonists, the low-affinity antagonist ZK98299 and the high-affinity antagonist RU486. The effect of ligand affinity on mobility was confirmed with the hGRalpha mutant Q642V, which has an altered affinity for triamcinolone acetonide, dexamethasone, and corticosterone. Analysis of hGRalpha deletion mutants indicates that both the DNA-binding domain and the ligand-binding domain of the receptor are required for a maximal ligand-induced decrease in receptor mobility. Interestingly, the mobility of transfected hGRalpha differs among cell types. Finally, the proteasome inhibitor MG132 immobilizes a subpopulation of unliganded receptors, via a mechanism requiring the DNA-binding domain and the N-terminal part of the ligand-binding domain. Ligand binding makes the GR resistant to the immobilizing effect of MG132, and this effect depends on the affinity of the ligand. Our data suggest that ligand binding induces a conformational change of the receptor which is dependent on the affinity of the ligand. This altered conformation decreases the mobility of the receptor, probably by targeting the receptor to relatively immobile nuclear domains with which it transiently associates. In addition, this conformational change blocks immobilization of the receptor by MG132.

Active Transport, Cell Nucleus↗

PubMed2002

Comparison of two methods used to assess first-ray mobility.

Mobility of the first-ray is associated with several common lower extremity disorders. However, the reliability and validity of clinical measurement remains unclear. In this study we examined first-ray mobility by using one hand to stabilize the lesser metatarsals while the clinician's other hand applied a displacement force to the head of the first metatarsal. The amount of mobility was graded as stiff, normal or hypermobile. We then used a well-validated mechanical device to perform similar tests and assessed validity, intrarater reliability and interrater reliability. Three clinicians having varied levels of experience graded first-ray mobility on 15 subjects. A separate investigator measured dorsal mobility with a mechanical device. Both methods of testing were repeated to assess measurement reliability. Reliability was estimated by kappa (K) statistics. Spearman correlation assessed the relationship between mobility graded manually and dorsal mobility measured by device. Manual examination intrarater K values ranged from 0.50 to 0.85, and interrater agreement from 0.09 to 0.16. Manual grading was not related (r = -0.21) to the absolute measure of total dorsal mobility made by device. This brings into question the validity and reliability of manual estimates of first-ray mobility.

Adult↗

PubMed2004

Dorsal mobility and first ray stiffness in patients with diabetes mellitus.

BACKGROUND: Limited joint mobility in diabetic patients has been identified as a risk factor in the development of plantar ulcers. We examined dorsal mobility and passive first ray stiffness in patients with diabetes and investigated the relationship between first ray mobility and ankle joint dorsiflexion. METHODS: Forty individuals were studied: 20 with diabetes (mean estimated duration of 16 +/- 10 years) and 20 matched controls. Dorsal first ray mobility was measured using a mechanical device. Force-vs-dorsal mobility displacement values were collected at 10 N increments to a load limit of 55 N. Ankle joint dorsiflexion motion was measured with a goniometer. The "prayer sign," a clinical indicator of limited joint mobility, was evaluated in each patient. Subjects were separated into the two groups for data analysis. RESULTS: Patients in the diabetic group had more stiffness and less dorsal first ray mobility than the control group (p <.05). In particular, patients with a positive prayer sign had significant first ray stiffness (p <.05). Patients with diabetes also had less ankle dorsiflexion (p <.05). CONCLUSION: Patients with diabetes have more stiffness and less first ray mobility and less ankle dorsiflexion than those without diabetes. The presence of a positive prayer sign correlates with stiffness and loss of first ray mobility. Soft-tissue stiffness may contribute to the development of foot ulcers in diabetic patients with neuropathy.

Adult↗