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PubMed1988

Anti-immunoglobulin pretreatment induces a calcium-mobilization response to the chemotactic agent N-formylmethionylleucylphenylalanine in Daudi lymphoblastoid cells.

Anti-immunoglobulin treatment of fura-2-loaded Daudi cells induces a calcium mobilization as judged by the increase in the fluorescence of the dye fura-2, AM. No calcium mobilization by N-fMet-Leu-Phe is observed in these cells. However, exposure of the cells to N-fMet-Leu-Phe after the first hit with anti-immunoglobulin (but not after soluble IgG) shows a rapid, dose-dependent calcium mobilization by N-fMet-Leu-Phe. The expression of the calcium-mobilizing response occurs in less than 2 min and is stable. Binding of tritiated N-fMet-Leu-Phe is increased in anti-immunoglobulin-treated but not control cells. The induction is specific for N-fMet-Leu-Phe because the chemoattractant platelet-activating factor did not induce any calcium mobilization. The N-fMet-Leu-Phe antagonist t-butoxycarbonyl-L-Phe-D-Leu-L-Phe-D-Leu-L-Phe- OH did not show any calcium mobilization on its own, either before or after anti-immunoglobulin treatment, and inhibited the calcium mobilization of N-fMet-Leu-Phe at low concentrations. Treatment of the cells with phorbol 12-myristate 13-acetate or pertussis toxin prior to anti-immunoglobulin treatment caused a dose-dependent abolition of both the anti-immunoglobulin-mediated calcium mobilization and the subsequent calcium mobilization by N-fMet-Leu-Phe. Metabolic inhibitors that act predominantly by lowering the ATP levels within the cell (iodoacetate, sodium fluoride, oligomycin, and 2-deoxyglucose) all produced a greater inhibition of the N-fMet-Leu-Phe-mediated calcium mobilization than the anti-immunoglobulin-mediated response. Lowering the temperature from 37 degrees C to 22 degrees C reduced the anti-immunoglobulin response and completely inhibited the expression of the N-fMet-Leu-Phe effect. Our results indicate that activation of the calcium-mobilization pathway in B cells by crosslinking of bound surface immunoglobulin causes an induction of N-fMet-Leu-Phe-sensitive calcium mobilization.

Antigen-Antibody Complex↗

PubMed1993

Maintaining mobility in late life. I. Demographic characteristics and chronic conditions.

To assess the role of demographic factors and chronic conditions in maintaining mobility in older persons, this study utilized longitudinal data collected as part of the Established Populations for Epidemiologic Studies of the Elderly between 1981 and 1987 on 6,981 men and women aged 65 years and older in East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. Results are presented for those who at baseline reported intact mobility, defined as the ability to climb stairs and walk a half mile without help, and who were followed annually for up to 4 years for changes in mobility status. Age, income, education, and chronic conditions present at baseline and occurring during follow-up were evaluated for their association with loss of mobility. Over the follow-up period, 55.1% of subjects maintained mobility, 36.2% lost mobility, and 8.7% died without evidence of mobility loss prior to death. In both men and women, increasing age and lower income levels were associated with increased risk of losing mobility, even after controlling for the presence of chronic conditions at baseline. After adjustment for age, income, and chronic conditions, lower education levels were a significant risk factor for mobility loss in men, but not in women. Baseline reports of previous heart attack, stroke, high blood pressure, diabetes, dyspnea, and exertional leg pain were associated with small but significant risks for mobility loss. There was a stepwise increase in the risk of mobility loss according to the number of chronic conditions present at baseline that was very consistent between men and women. The occurrence during the study of a new heart attack, stroke, cancer, or hip fracture was associated with a substantially greater risk of mobility loss than was associated with the presence of these conditions at baseline.

Activities of Daily Living↗

PubMed1998

Assessment of ejaculate quality and sperm characteristics in turkeys: sperm mobility phenotype is independent of time.

Given a pool of genetically superior male turkeys, the subsequent selection of toms as semen donors for artificial insemination should be based upon criteria that are predictive of the tom's fertility and fecundity over the course of a production cycle. Recently, sperm mobility phenotype has been shown to correlate highly with fertility. Therefore, the objectives of this study were to determine: 1) whether sperm mobility phenotypes of individual toms were independent of time, and 2) the extent to which traditional semen quality variables changed as a function of time during the study interval. Sperm mobility phenotype was determined by objectively measuring the ability of sperm to penetrate 2% Accudenz solution at body temperature. During the initial assessments of a flock (n = 94), sperm mobility indexes (SMI) were significantly higher for the High Mobility Phenotype toms (56.61 +/-1.03% SMI) compared to the Low Mobility Phenotype (30.46+/-1.27% SMI, P < or = 0.0001) toms. Over the 5 mo of this study, the High Mobility Phenotype toms consistently had higher (P < or = 0.05) SMI values than the Low Mobility Phenotype toms, with SMI values similar to those of the initial screen. Ejaculate volume, concentration, and plasma membrane integrity showed no significant differences between phenotypes (P > or = 0.05). Sperm viability remained significantly lower (P < or = 0.05) over the course of this study for the High Mobility Phenotype toms than for the Low Mobility Phenotype toms. Because sperm mobility phenotype remained consistent through time, the Sperm Mobility Test provides a potentially important tool for selecting semen donors in turkeys.

Animals↗

PubMed2001

Headache, neck pain, and neck mobility after acute whiplash injury: a prospective study.

STUDY DESIGN: A 6-month prospective study of neck mobility in patients with acute whiplash injury and a control group with acute ankle distortion was conducted. OBJECTIVES: To assess active neck mobility after acute whiplash and ankle distortion injuries, and to relate neck mobility to headache, neck pain, and speed of car at the time of collision. SUMMARY OF BACKGROUND DATA: A major problem after whiplash injury is restriction of neck mobility immediately subsequent to trauma. It is, however, unclear whether neck mobility changes after the acute injury are related to the associated headache and neck pain. METHODS: Cervical range of neck motion, neck pain, and headache were assessed after 1 week, then 1, 3, and 6 months after injury in 141 patients with acute whiplash injury, and in 40 patients with acute nonsport ankle distortion. RESULTS: Patients with whiplash injury had significantly reduced flexion, extension, lateral flexion, and rotation of the neck immediately after injury, as compared with patients with ankle distortion injury. Neck mobility, however, was similar in the two groups after 3 months. In patients with whiplash injury, neck pain and neck mobility were found to be related inversely to reported headache and neck mobility. Neck mobility was not significantly related to a difference in car speed at the time of collision. CONCLUSIONS: Neck mobility is reduced immediately after, but not 3 months after, a whiplash trauma. Headache and neck mobility are related inversely and neck pain and neck mobility are related inversely during the first 6 months after acute whiplash injury.

Acute Disease↗

PubMed1999

Sperm mobility determines the outcome of sperm competition in the domestic fowl.

The aim of this study was to establish whether the mobility of sperm of the domestic fowl, as measured by an in vitro assay, predicted the outcome of sperm competition. Thirteen pairs of New Hampshire roosters, comprising one male categorized as having high-mobility sperm and the other as having average-mobility sperm, were used. Each male provided 25 x 10(6) sperm, which were mixed and artificially inseminated into between four and seven New Hampshire hens, each of which produced 2-11 offspring. The experiment was conducted twice, such that the same pair of males inseminated the same females. Paternity was assigned by using microsatellite markers. There was a clear effect of sperm-mobility phenotype on the outcome of sperm competition: in all 13 pairs the high-mobility male fathered the majority of offspring (75.3% overall; p < 0.0001). The proportion of offspring fathered by the high-mobility male within pairs varied significantly between male pairs (p < 0.0005). This effect was associated with the difference in sperm-mobility scores between males within pairs; there was a significant positive relationship between the proportion of offspring fathered by the high-mobility male and the ratio of mobility scores between males (p < 0.05). In addition, compared with their success predicted from the non-competitive situation, in the competitive situation high-mobility males were disproportionately successful in fertilizing eggs compared with average-mobility males. This may occur because female sperm storage is limited in some way and a greater proportion of high-mobility sperm gain access to the female's sperm storage tubules. There was no evidence that female effects accounted for any of the variation in paternity.

Animals↗

PubMed2003

Ion mobilities in Xe/Ne and other rare-gas mixtures.

The ion mobility or drift velocity data important for modeling glow discharges in rare gas mixtures are not generally available, nor are the ion-neutral scattering cross sections needed to calculate these data. In this paper we propose a set of cross sections for Xe+ and Ne+ collisions with Xe and Ne atoms. Ion mobilities at 300 K calculated using this cross section set in a Monte Carlo simulation are reported for reduced field strengths, E/N, up to 1500 x 10(-21) V m(2), in pure gases and in Xe/Ne mixtures containing 5% and 20% Xe/Ne, which are mixtures of interest for plasma display panels (PDPs). The calculated Xe+ mobilities depend strongly on the mixture composition, but the Ne+ mobility varies only slightly with increasing Xe in the mixture over the range studied here. The mobilities in pure gases compare well with available experimental values, and mobilities in gas mixtures at low E/N compare well with our recent measurements which will be published separately. Results from these calculations of ion mobilities are used to evaluate the predictions of Blanc's law and of the mixture rule proposed by Mason and Hahn [Phys. Rev. A 5, 438 (1972)] for determining the ion mobilities in mixtures from a knowledge of the mobilities in each of the pure gases. The mixture rule of Mason and Hahn is accurate to better than 10% at high field strengths over a wide range of conditions of interest for modeling PDPs. We conclude that a good estimate of ion mobilities at high E/N in Xe/Ne and other binary rare gas mixtures can be obtained using this mixture rule combined with known values of mobilities in parent gases and with the Langevin form for mobility of rare gas ions ion in other gases. This conclusion is supported by results in Ar/Ne mixtures which are also presented here.

Journal Article↗

PubMed2004

Prevalence and outcomes of low mobility in hospitalized older patients.

OBJECTIVES: To estimate the prevalence of different levels of mobility in a hospitalized older cohort, to measure the degree and rate of adverse outcomes associated with different mobility levels, and to examine the physician activity orders and documented reasons for bedrest in the lowest mobility group. DESIGN: A prospective cohort study. SETTING: An 800-bed university teaching hospital. PARTICIPANTS: Four hundred ninety-eight hospitalized medical patients, aged 70 and older. MEASUREMENTS: Using average mobility level, scored from 0 to 12, the low-mobility group was defined as having a score of 4 or less, intermediate as a score of higher than 4 to 8, and high as higher than 8. Outcomes were functional decline, new institutionalization, death, and death or new institutionalization. RESULTS: Low and intermediate levels of mobility were common, accounting for 80 (16%) and 157 (32%) study patients, respectively. Overall, any activity of daily living (ADL) decline occurred in 29%, new institutionalization in 13%, death in 7%, and death or new institutionalization in 22% of patients in this cohort. When compared with the high mobility group, the low and intermediate groups were associated with the adverse outcomes in a graded fashion, even after controlling for multiple confounders. The low-mobility group had an adjusted odds ratio (OR) of 5.6 (95% confidence interval (CI)=2.9-11.0) for ADL decline, 6.0 (95% CI=2.5-14.8) for new institutionalization, 34.3 (95% CI=6.3-185.9) for death, and 7.2 (95% CI=3.6-14.4) for death or new institutionalization. The intermediate group had adjusted ORs of 2.5 (95% CI=1.5-4.1), 2.9 (95% CI=1.4-6.0), 10.1 (95% CI=1.9-52.9), and 3.3 (95% CI=1.8-5.9) for ADL decline, new institutionalization, death, and death or new institutionalization, respectively. Bedrest was ordered at some point during hospitalization in 165 (33%) patients. For most patients, mobility was limited involuntarily (bedrest orders), and almost 60% of bedrest episodes in the lowest mobility group had no documented medical indication. CONCLUSION: Low mobility and bedrest are common in hospitalized older patients and are important predictors of adverse outcomes. This study demonstrated that the adverse outcomes associated with low mobility and bedrest may be viewed as iatrogenic events leading to complications, such as functional decline.

Activities of Daily Living↗

PubMed1992

Cytotoxic drug and cytotoxic drug/G-CSF mobilization of peripheral blood stem cells and their use for autografting.

We analysed 99 courses of leukapheresis after the use of cytotoxic drugs or cytotoxic drugs plus G-CSF (cytotoxic/G-CSF) to mobilize peripheral blood stem cells (PBSC) in 68 patients with hematologic or solid malignancies. Mean yields of granulocyte-macrophage progenitor cells (CFU-GM) with cytotoxic/G-CSF mobilization were significantly higher than those with cytotoxic mobilization (18.6 vs 8.40 x 10(4)/kg). The optimal timing of collection was different between these two mobilizations; the mean number of days to a peak level of circulating CFU-GM after cytotoxic/G-CSF mobilization was less than that after cytotoxic mobilization (24.2 vs 27.7 days). The leukocyte level on the day of peak CFU-GM was significantly higher in cytotoxic/G-CSF mobilization than that in cytotoxic mobilization (mean 12.8 vs 2.7 x 10(9)/l), whereas the platelet level was not different (mean 132 vs 125 x 10(9)/l). Increasing patient age was not a major adverse factor for PBSC collection. Synchronous recovery of both leukocytes and platelets was critical for achieving a high CFU-GM yield in these two mobilizations. Following PBSC autotransplantation, the rate of trilineage hematologic reconstitution showed a significant correlation with the infused dose of CFU-GM, whether they were collected with cytotoxic or cytotoxic/G-CSF mobilization. These results suggest that G-CSF can expand the PBSC pool and that CFU-GM yield after cytotoxic/G-CSF mobilization may predict trilineage hemopoietic reconstitution after ABSCT, as well as cytotoxic mobilization.

Adolescent↗

PubMed2004

The performance of infants born preterm and full-term in the mobile paradigm: learning and memory.

BACKGROUND AND PURPOSE: By 3 to 4 months of age, infants born full-term and without known disease display associative learning and memory abilities in the mobile paradigm, where an infant's leg is tethered to a mobile such that leg kicks result in proportional mobile movement. The first purpose of this study was to examine the learning and memory abilities of a group of infants born full-term compared with those of a comparison group. Little is known about the learning and memory abilities in infants born preterm, a group at known risk for future impairments in learning and movement. The second purpose of this study was to determine if and when an age-adjusted group of infants born prematurely display associative learning and memory abilities over a 6-week period. SUBJECTS: Ten infants born full-term (38-42 weeks gestational age [GA]) and 10 infants born preterm (<33 weeks GA and <2,500 g) who were tethered and had control over the mobile movement were independently compared with a comparison group of 10 infants born full-term who were tethered and viewed a moving mobile but did not have control over the mobile movement. Infants in all 3 groups were seen at 3 to 4 months of age and were excluded from participation for any known visual or orthopedic diagnoses. METHODS: Infants were tested using the mobile conjugate reinforcement paradigm, where one leg is tethered to an overhead mobile such that kicking with that leg results in proportional mobile movement. The kicking rates of the full-term group and the preterm group were compared with their own initial (baseline) kicking rates and with those of the comparison group. RESULTS: After exposure to the conjugate relationship between kicking and mobile movement, the full-term group kicked more frequently compared with their own baseline levels and compared with the comparison group, fulfilling both criteria for learning and memory. In contrast, the preterm group did not increase their kicking rate according to both criteria. DISCUSSION AND CONCLUSION: These results suggest that infants born prematurely differ in their performance in the mobile paradigm as compared with age-matched infants born full-term. The mobile paradigm may provide clinicians with an important early assessment of infants' associative learning and memory abilities. Follow-up studies are needed, however, to further validate this paradigm as a clinical assessment tool.

Analysis of Variance↗

PubMed1981

Changes in lectin receptor lateral mobilities accompany lymphocyte stimulation.

Changes in lateral mobilities of rabbit lymphocyte membrane components in response to succinyl concanavalin A (S Con A) have been studied by fluorescence photobleaching recovery (FPR). During hrs 0 to 3 after exposure to S Con A, lectin receptor mobilities on both T and B cells fall about 2-fold. Reduced mobility of T cell lectin receptors persists until hr 18. From hr 18 to 24 rapid recovery of original mobility occurs if and only if lectin is present. In contrast, nonresponding B cells recover original receptor mobility gradually over hr 4 to 48. Metabolic inhibitors added at hr 3 restore original receptor mobilities, but cytoskeletal disruptors have this effect on T cells only. From hr 0 to 15, washing lectin from the cell surface is decreasingly effective in restoring T cell receptor mobility. After hr 15, mobility cannot be enhance by lectin removal. Parallel DNA synthesis studies show that, for T cell stimulation, lectin must be present on the cell surface during hr 0 to 3 and 18 to 24. These are the periods when FPR measurements show lectin receptor mobilities being restricted and released, respectively. Stimulation of B cells by anti-Ig shows several interesting features. First, stimulation by intact anti-Ig fails to reduce the mobilities of Con A receptors in a manner similar to that produced by S Con A. Second, S Con A does reduce mobility of surface Ig. Thus, Con A receptors would appear to exert a unique anchorage modulation of mobilities of other membrane molecules.

Animals↗

PubMed1994

Comparison of mobility changes with histological and biochemical changes during lipopolysaccharide-induced arthritis in the hamster.

Arthritis refers to a heterogeneous class of diseases characterized by impairment of movement. Yet animal models of arthritis have traditionally been based on the utilization of animals housed without the capability of extended free movement and without adjunctive measurement of mobility. To define the determinants of mobility impairment, we have established a lipopolysaccharide (LPS)-induced arthritis model in the hamster that prominently features monitoring of mobility and compares mobility changes with histological and biochemical changes during arthritis. Intraarticular LPS induces a dose-dependent inhibition of the hamster's mobility as measured by decreased daily distance on a running wheel (normal distance 9 to 12 km/day). At low concentrations of LPS (0.1 and 1 microgram/knee), daily distances returned to normal after 4 and 6 days, respectively. At higher concentrations, the mobility was still markedly suppressed after 6 days, and, at 100 micrograms/knee, irreversible chondrocyte loss was observed on the femoral condylar margins. Further studies were therefore conducted using 1 microgram LPS/knee. Histological and biochemical changes were examined to determine which resolved at the time of restoration of mobility. At the time of restoration of mobility, the synovial capsule was still edematous and heavily infiltrated with leukocytes; proteoglycan loss from the medial femoral condyle was still increasing. Plasma keratan sulfate failed to correlate with either proteoglycan loss or mobility changes. Proteoglycan synthesis, which was maximally suppressed the second day after LPS, was enhanced over controls at the time of restoration of mobility, suggesting the onset of repair. These results suggest a possible association of mobility inhibition with local cytokine synthesis. This model provides an approach to define the causes of mobility impairment.

Animals↗

PubMed1998

Social mobility and 21 year mortality in a cohort of Scottish men.

The objective of this prospective cohort study was to determine the contribution of changes in social class within and between generations to mortality risk and to socioeconomic differentials in mortality. In 27 workplaces in the west of Scotland. 5567 men aged 35-64 years when screened, provided information on their father's occupation, their own first occupation and their occupation at screening. Mortality risk, from broad causes of death by intergenerational and intragenerational social mobility groups, was measured after 21 years. For all or some of the 3 routes of mobility (childhood to screening, labour market entry to screening and childhood to labour market entry), increasing values were seen across the 4 groups (stable non manual, upwardly mobile, downwardly mobile and stable manual) for diastolic blood pressure, body mass index, current smoking, early school leaving, angina, bronchitis, severe chest pain, and proportion living in deprived areas. Decreasing values were seen for serum cholesterol, height, FEV1, exercise, never and ex-smokers, wine drinkers and car users. For mobility between childhood and screening and between childhood and labour market entry, mortality risk was highest for the stable manual group and lowest for the stable non manual group for all cause, cardiovascular disease and other causes of death. The upwardly and downwardly mobile groups had intermediate risks. For cancer mortality, the stable manual group had the highest risk with the other groups having lower and similar risks. For mobility between labour market entry and screening, the highest risk was for the downwardly mobile group for all cause and cardiovascular mortality. For cancer mortality, the risk was higher for men in manual social classes at all occasions. Adjustment for risk factors attenuated but could not completely explain the differentials in mortality risk. Overall, major differences in mortality risk were seen between the stable non manual and the stable manual groups, to which social mobility does not contribute. With the exception of the small intragenerationally downwardly mobile group there was little evidence that social mobility itself was associated with mortality outcomes different from those expected on the basis of lifetime socioeconomic experience. This is consistent with the suggestion that the main influence of socioeconomic position on mortality risk is an accumulative one, acting across the lifecourse.

Adult↗

PubMed1999

The "G-CSF test": the response to a single dose of granulocyte colony-stimulating factor predicts mobilization of hemopoietic progenitors in patients with hematologic malignancies.

A significant proportion of patients with hematologic malignancies fail to mobilize sufficient hemopoietic progenitor cells (HPC), thereby restricting wider application of autologous transplantation. It would be of considerable use to develop a test that could be used prospectively to assess an individual patient's capacity to mobilize HPC. Twenty-two patients with lymphoma, myeloma, and chronic lymphocytic leukemia were given a single dose of 12 microg/kg SC of granulocyte colony-stimulating factor (G-CSF). Blood colony-forming unit granulocyte-macrophage (CFU-GM) and CD34+ cells were scored prior to the test dose, and 72, 96, and 120 hours later. The patients were then mobilized with a standard cyclophosphamide and G-CSF regimen and had blood stem cells harvested. Patients were categorized as good, poor, or intermediate mobilizers on the basis of the CFU-GM/CD34+ cell harvest content and the number of aphereses required to reach established threshold counts. The outcome of cyclophosphamide/G-CSF mobilization was correlated with the response to the test dose of G-CSF. Good mobilizers had significantly higher peak CFU-GM values and CFU-GM increment in response to the test dose of G-CSF compared to intermediate and poor mobilizers. A peak CFU-GM count of > or = 250/mL identified the good mobilizers; conversely, all poor mobilizers had a peak CFU-GM count of <102/mL. An increment in CD34+ cells counts of > or = 2.5/microL was only observed in good mobilizers. The "G-CSF" test is a reliable test that can be used successfully for the assessment of mobilizable HPC in patients with hematologic malignancies. It can also be used to stratify patients enrolled in trials of mobilizing agents.

Adult↗

PubMed2000

Favorable treatment outcome in non-Hodgkin's lymphoma patients with "poor" mobilization of peripheral blood progenitor cells.

Our purpose was to evaluate the outcome and costs of high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation in patients with the inability to mobilize sufficient numbers of PBPCs to allow rapid engraftment after PBPC transplantation. We treated 172 consecutive non-Hodgkin's lymphoma (NHL) patients with cyclophosphamide and granulocyte colony-stimulating factor followed by apheresis to collect PBPCs. The cells were separated on a Percoll gradient and purged with monoclonal antibodies and complement. The patients were categorized as "good" mobilizers if a collection of > or =2 x 10(6) CD34+ cells/kg was obtained (n = 138, 80%) or "poor" mobilizers if <2 x 10(6) CD34+ cells/kg were obtained (n = 34, 20%). With a median follow-up of 3.5 years, there is no statistically significant difference in actuarial event-free survival, overall survival, or relapse for good mobilizers compared with poor mobilizers. However, there was a trend toward increasing nonrelapse, transplantation-related mortality of 11.8% for poor mobilizers versus 3.6% for good mobilizers (P = .08) and early death from all causes including relapse within 120 days (poor 20.6% versus good 8.7%, P = .06). The total cost for bone marrow transplantation-related care was significantly higher, at $140,264 for poor mobilizers versus $80,833 for good mobilizers (P = .0001). The population of patients with NHL who mobilize PBPCs poorly into the circulation have a higher cost for posttransplant support. However, there is no significant difference in relapse, event-free survival, or overall survival for such patients compared with those who mobilize PBPCs easily.

Adult↗

PubMed2001

Industrialization, class structure, and social mobility in postwar Japan.

This study examines intergenerational class mobility in Japan using cross-national comparisons with Western nations and cross-temporal comparisons of five national surveys conducted in postwar Japan. Cross-national comparisons highlight the similarity in relative mobility pattern between Japan and Western nations and at the same time the Japanese distinctiveness in absolute mobility rates especially regarding the demographic character of the Japanese manual working class. The results of cross-temporal comparisons of mobility pattern report some systematic trends in total mobility, inflow and outflow rates, reflecting the Japanese experience of late but rapid industrialization. The pattern of association between class origin and class destination, however, was stable in postwar Japan. It is therefore the combination of distinctive absolute mobility rates and similar relative mobility rates that characterizes the Japanese mobility pattern in comparison with the Western experience. Furthermore, Japan's distinctive pattern of postwar social mobility is characterized by a combination of rapidly changing absolute mobility rates and comparatively stable relative mobility rates.

Humans↗

PubMed1998

Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells: an effect mediated by a circulating factor.

Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 microg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 microg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.

Animals↗

PubMed2005

Hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor and erythropoietin in the absence of matrix metalloproteinase-9.

The use of mobilized hematopoietic progenitor cells (HPC) has largely replaced the use of bone marrow HPC for autologous and allogeneic transplantation; however, the mechanisms of HPC mobilization remain unclear. A better understanding of these mechanisms, may allow the development of improved (potentially more rapid and/or higher yield) HPC mobilization strategies, especially for patients who mobilize poorly using current mobilization protocols. Clinically, granulocyte colony-stimulating factor (G-CSF) is widely used to induce HPC mobilization, and evidence suggests that metalloproteinase enzymes released by activated granulocytes play an important role in the G-CSF-induced HPC mobilization. These enzymes may act to disrupt putative cell-cell and/or cell-extracellular matrix interactions within the hematopoietic microenvironment thereby releasing HPC into the blood. Matrix metalloproteinase-9 (MMP-9) appears to be important for G-CSF-induced mobilization. Using an MMP-9 knock-out (KO) mouse model, we investigated the role of MMP-9 in G-CSF and erythropoietin (EPO)-based HPC mobilization at clinically relevant cytokine doses. There were few hematologic or hematopoietic differences between the wild-type and MMP-9KO mice during steady-state hematopoiesis. When treated subcutaneously with EPO (500 U/kg per day) and G-CSF (15 microg/kg per day) for 5 days and assayed on day 6, similarly increased extramedullary hematopoiesis and numbers of HPC in the spleen and blood were observed for both the wild-type and MMP-9KO mice. These data demonstrate that MMP-9 is not required for EPO + G-CSF mobilization and that alternative mobilization mechanisms must be active at clinically relevant cytokine concentrations.

Animals↗

PubMed1999

Social mobility and health related behaviours in young people.

STUDY OBJECTIVE: To assess the influences related to social mobility, particularly health related behaviours, as one potential explanation for the social class variation in health among adults. DESIGN: The study is based on questionnaire data from the Adolescent Health and Lifestyle Surveys of 1985, 1987, and 1989. SETTING: The whole of Finland. PARTICIPANTS: A representative sample of 8355 adolescents. The response rate was 79%. MEASUREMENT AND MAIN RESULTS: The relation between social mobility and health related behaviours among 16 and 18 year old young people was studied. The measure of social mobility was based on a combination of the social class of origin and achieved social position measured by the present educational status, educational attainment, and labour market position. Three mobility groups were constructed: the downwardly mobile, the upwardly mobile and the stable. Health related behaviours in an upwardly or downwardly mobile group were compared with a stable group from the same social class of origin by calculating relative risks (RR). RRs were assessed by calculating age and sex adjusted rate ratios approximating a Mantel-Haenszel estimate. In logistic regression analyses the independent effects of the social class of origin and the achieved social position were investigated. Most of the nine behaviours studied (smoking, alcohol use, heavy intoxication, coffee drinking, tooth brushing, consumption of sweets, lack of physical exercise, choice of bread spread, and consumption of milk) were related to the direction of mobility so that health compromising behaviours were more frequent among downwardly mobile and less frequent among upwardly mobile young people than their stable peers. Achieved social position proved to determine health related behaviours more strongly than class of origin, thus emphasising the way education facilitates both health values and behaviours as well as the future social position. CONCLUSIONS: The close relation between social mobility and health related behaviours is concluded to be a part of an explanation of social class differences in health observed among adults.

Adolescent↗