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At least 667 records · Page 37Linked to original sources

PubMed2005

Role of CXCR4 chemokine receptor blockade using AMD3100 for mobilization of autologous hematopoietic progenitor cells.

G-CSF mobilization of hematopoietic progenitor cells (HPCs) is mediated through enzyme release from maturing myeloid cells, leading to digestion of adhesion molecules, trophic chemokines and their receptors, and the extracellular matrix. HPCs traffic to and are retained in the marrow through the trophic effects of the chemokine SDF-1alpha/CXCL12 binding to its receptor, CXCR4. AMD3100 reversibly inhibits SDF-1alpha/CXCR4 binding, and AMD3100 administration mobilizes CD34+ cells into the circulation. AMD3100 has been tested in several clinical trials which demonstrate that it improves the number of CD34+ cells mobilized including patients failing to mobilize with G-CSF alone. Engraftment of AMD3100-mobilized cells is prompt and durable. Toxicities are mild and infrequent. Lymphoma and myeloma cells do not appear to be mobilized. AMD3100 appears to be a promising agent for HPC mobilization.

Anti-HIV Agents↗

PubMed2003

Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide.

Hematopoietic progenitor cells (HPCs) normally reside in the bone marrow (BM) but can be mobilized into the peripheral blood (PB) after treatment with GCSF or chemotherapy. In previous studies, we showed that granulocyte precursors accumulate in the BM during mobilization induced by either GCSF or cyclophosphamide (CY), leading to the accumulation of active neutrophil proteases in this tissue. We now report that mobilization of HPCs by GCSF coincides in vivo with the cleavage of the N-terminus of the chemokine receptor CXCR4 on HPCs resident in the BM and mobilized into the PB. This cleavage of CXCR4 on mobilized HPCs results in the loss of chemotaxis in response to the CXCR4 ligand, the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). Furthermore, the concentration of SDF-1 decreased in vivo in the BM of mobilized mice, and this decrease coincided with the accumulation of serine proteases able to directly cleave and inactivate SDF-1. Since both SDF-1 and its receptor, CXCR4, are essential for the homing and retention of HPCs in the BM, the proteolytic degradation of SDF-1, together with that of CXCR4, could represent a critical step leading to the mobilization of HPCs into the PB in response to GCSF or CY.

Animals↗

PubMedDate not supplied

The safety of performing diagnostic cardiac catheterizations in a mobile catheterization laboratory at primary care hospitals.

The benefits of mobile cardiac catheterization laboratories include keeping patients closer to their families, communities, local hospitals, and primary care physicians while receiving services comparable to those available at tertiary centers. However, there are very few studies regarding the safety of performing cardiac catheterization in mobile laboratories at remote locations. Thus, the authors performed an observational study of 1,775 consecutive patients undergoing a diagnostic cardiac catheterization in a mobile catheterization laboratory at primary care hospitals served by the Appleton Heart Institute (AHI) from August 1, 1991, to December 31, 1998. Twenty-three percent (1,775/7,637) of all AHI diagnostic cases in this time period were performed in the mobile catheterization laboratory. Urgent transfer to the tertiary care facility via ambulance or helicopter was used for 2.3% of patients (n = 41). The overall complication rate was 1.2% (n = 21). Of the patients who underwent cardiac catheterization in the mobile laboratory, 32.6% (n = 579) were subsequently referred for interventional or surgical revascularization. There were no deaths. Cardiac catheterizations can be performed safely in a mobile laboratory at primary care hospitals, provided that immediate transfer is available for those in need of urgent intervention or revascularization and that unstable patients are not studied in the mobile laboratory.

Adult↗

PubMed2005

Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model.

Peripheral-blood mononuclear cells (PBMCs) mobilized with AMD3100, a CXCR4 antagonist, combined with granulocyte colony-stimulating factor (G-CSF) have reconstituted autologous hematopoiesis in cancer patients following myeloablative conditioning. The engraftment potential of PBMCs mobilized with AMD3100 alone, however, has remained unproven. We therefore studied AMD3100-mobilized PBMCs in a canine model. Four dogs received 920 cGy total body irradiation (TBI) before infusion of autologous AMD3100-mobilized PBMCs (median CD34 cell count, 3.9 x 10(6)/kg). Neutrophil (> 0.5 x 10(9)/L [500/microL]) and platelet (> 20 x 10(9)/L [> 20 000/microL]) recoveries occurred at medians of 9 (range, 7-10) days and 25 (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow function at 1 year after transplantation. To evaluate the long-term engraftment potential of AMD3100-mobilized PBMCs, 5 dogs were given 920 cGy TBI followed by infusion of AMD3100-mobilized PBMCs (median CD34 cell dose, 4.7 x 10(6)/kg) from their dog leukocyte antigen (DLA)-identical littermates. Neutrophil and platelet recoveries occurred at medians of 8 (range, 8-10) days and 26 (range, 26-37) days, respectively, after TBI. With a median follow-up of 53 (range, 33-61) weeks, recipients' marrow function was normal, and blood-donor chimerism levels were 97% to 100%. In summary, both autologous and allogeneic AMD3100-mobilized PBMCs led to prompt and durable engraftment in dogs after 920 cGy TBI.

Animals↗

PubMed2001

Synergistic mobilization of hemopoietic progenitor cells using concurrent beta1 and beta2 integrin blockade or beta2-deficient mice.

The hierarchy of cytoadhesion molecules involved in hematopoietic/stem progenitor cell mobilization has not yet been delineated. Previous studies have suggested an important role for alpha4beta1 integrin in this process. To test whether mobilization involves dynamic interactions of alpha4beta1 with other integrins on hematopoietic cells, especially the beta2 integrins, mice and primates were treated with anti-beta1 or anti-beta2 antibodies alone or in combination. A single injection of anti-alpha4beta1 antibody elicited reproducible mobilization in contrast to other antibodies, and 3 injections yielded higher mobilization efficiency than each of the other antibodies. When the anti-beta2 (anti-CD11a or anti-CD18) or anti-alpha5/beta1 integrin antibody was combined with anti-alpha4, an augmentation in mobilization was seen that was either additive or synergistic, depending on the potency of the antibody used. Synergy between anti-alpha4 and anti-CD18 (beta(2)) antibody blockade was seen in primates and confirmed in anti-alpha4-treated CD18-deficient mice. In the latter, there was a 49-fold increase in mobilization with anti-alpha4, much higher than in littermate control animals, in CD18 hypomorphic mice, or in other strains of mice tested. Data from both the antibody blockade and gene-targeted mice suggest that the cooperativity of alpha4beta1 with beta2 integrins becomes evident when they are concurrently inhibited. It is unclear whether this cooperativity is exerted at the stage of reversible adhesion versus migration, and enhancement of and whether the 2 integrins work in a sequential or parallel manner. Whatever the mechanism, the data provide a novel example of beta1 and beta2 integrin crosstalk in stem/progenitor cell mobilization.

Animals↗

PubMed2003

Kinetics of peripheral blood stem cell mobilization following G-CSF-supported chemotherapy.

It would be a clinical and economical advantage if the optimal time point of peripheral blood stem cell (PBSC) mobilization following G-CSF-supported chemotherapy (CT) was known in advance. Therefore, we retrospectively analyzed mobilization parameters in 113 adult tumor patients treated in our institution within 1 year. The start of apheresis was guided by CD34(+) cell measurements in the PB and occurred on or after day 11 after start of mobilization CT in 97% of patients. The median peak (p)CD34(+) cell count in PB uniformly occurred on day 14-15 (range: 6-32 days) after the start of CT, irrespective of the diagnosis (multiple myeloma n = 76, other histology n = 37), the type, but not the amount, of premobilization CT or radiotherapy (RT), the mobilization regimen, or the G-CSF dosage administered. Among more heavily pretreated patients (>six cycles of prior CT or RT), a higher proportion mobilized late (pCD34(+) cell count later than day 20 in 12% and 13%, respectively, versus 2%-5% in the other groups). Therefore, we propose to start measuring CD34(+) cells in the PB on day 11 after the start of mobilization therapy. The wide range of optimal mobilization time points argues for an individualized rather than a preset start of apheresis.

Adult↗

PubMed1975

An evaluation of clinical tooth mobility measurements.

This study evaluated the reliability and reproducibility of the modified Miller Index of horizontal tooth mobility. Each of three periodontists utilizing the modified Miller Index assessed the horizontal tooth mobility of 50 teeth in five subjects. The same teeth were also evaluated by the periodontometer. The results of these two methods were then compared. It was found that: (1) there were a high positive correlation between the periodontists' (pooled) assessment of clinical tooth mobility and the measurements of the periodontometer, (2) in any given patient the three periodontists (pooled) were highly accurate in their ability to rank teeth in order of their mobility as determined by the periodontometer, and (3) the periodontists (individually) were not as consistent when comparing teeth with the Miller Index across different subjects. The periodontists did not accurately utilize the Miller Index as it was originally described. It appears that the periodontists either ignored the reference to 1 mm in the description of the Miller Index, or they were unable to estimate what constitutes 1 mm of movemnet in the mouth. The periodontists all consistently scored as a 2 degrees mobility a tooth that moved approximately 0.5 mm not 1.0 mm as described by Miller. It is suggested that the modified Miller Index as described here provides an efficacious system for evaluating horizontal tooth mobility. It provides accurate, reproducible mobility scores in clinical studies requiring an estimation of this parameter. However, for individual teeth, when the clinician or researcher is trying to evaluate the effects of therapy on the periodontium and relatively few evaluation are made, the modified Miller Index may not provide the required degree of sensitively.

Adult↗

PubMed2004

Favorable periodontal regenerative outcomes from teeth with presurgical mobility: a retrospective study.

BACKGROUND: The relevance of tooth mobility on periodontal healing is still controversial. The purpose of the present study was to evaluate the effect of presurgical tooth mobility on periodontal regenerative outcomes. METHODS: The data in this study were derived from three randomized clinical trials which evaluated regenerative procedures. Sixty-four patients with one intraosseous periodontal defect each received one of the following treatments: guided tissue regeneration (GTR) using expanded polytetrafluoroethylene (ePTFE), GTR using a bioabsorbable membrane with or without demineralized freeze-dried bone allograft (DFDBA), or enamel matrix derivative with or without DFDBA. Probing depth (PD), clinical attachment level (CAL), recession (REC), and tooth mobility (TM) were recorded at baseline and 1 year after treatment by a calibrated examiner. The post-surgical follow-up and maintenance periods were designed to optimize plaque control. The teeth were grouped according to their baseline Miller index TM score. The grouping yielded 36 teeth with minimal mobility, score 0; 13 teeth with score 1; and 15 with score 2. The mean changes in PD, CAL and REC from baseline to 1 year were calculated for each group. One-way analysis of variance (ANOVA) was performed to assess differences between the tooth mobility groups considering changes in PD, CAL, and REC at 1 year. RESULTS: The mean PD reduction from baseline to 1 year for teeth with TM score 0 was 3.67 mm; for TM score 1, 2.81 mm; and for score 2, 3.73 mm. The corresponding values for the gain in CAL were 2.73, 1.96, and 2.36 mm, respectively. According to ANOVA, the probing depth reductions and clinical attachment level gains found in each group were not statistically different, P= 0.218 and P= 0.252, respectively. CONCLUSION: Within the limitations of this analysis, it can be concluded that interproximal, intraosseous defects of teeth with limited presurgical tooth mobility; i.e., teeth with Miller's Class 1 and 2 mobility, will respond favorably to regenerative therapy.

Adult↗

PubMed2005

Mobilization of human lymphoid progenitors after treatment with granulocyte colony-stimulating factor.

Hemopoietic stem and progenitor cells ordinarily residing within bone marrow are released into the circulation following G-CSF administration. Such mobilization has a great clinical impact on hemopoietic stem cell transplantation. Underlying mechanisms are incompletely understood, but may involve G-CSF-induced modulation of chemokines, adhesion molecules, and proteolytic enzymes. We studied G-CSF-induced mobilization of CD34+ CD10+ CD19- Lin- and CD34+ CD10+ CD19+ Lin- cells (early B and pro-B cells, respectively). These mobilized lymphoid populations could differentiate only into B/NK cells or B cells equivalent to their marrow counterparts. Mobilized lymphoid progenitors expressed lymphoid- but not myeloid-related genes including the G-CSF receptor gene, and displayed the same pattern of Ig rearrangement status as their bone marrow counterparts. Decreased expression of VLA-4 and CXCR-4 on mobilized lymphoid progenitors as well as multipotent and myeloid progenitors indicated lineage-independent involvement of these molecules in G-CSF-induced mobilization. The results suggest that by acting through multiple trans-acting signals, G-CSF can mobilize not only myeloid-committed populations but a variety of resident marrow cell populations including lymphoid progenitors.

Animals↗

PubMed1985

Distinctively elderly mobility: types and determinants.

"Distinctive types of mobility are identified for the [U.S.] elderly, many of whom also move for traditional reasons. Using a longitudinal data set from adult residents in Rhode Island, univariate, chi square, and logit analyses indicate associations between sociodemographic characteristics of the elderly and their mobility behavior. Mobility for assistance reasons is associated with older age, unmarried status, higher previous mobility, and renter status. Mobility in preparation for aging (e.g., to an elderly complex) is more likely for unmarried, previously mobile residents. Out-of-state mobility to amenity destinations is not limited to the elderly, but younger, married, more affluent elderly were more likely to make such moves."

Adult↗

PubMed2002

[Change of adhesion molecule expression on CD34(+) cells from bone marrow and peripheral blood during mobilization with combination of chemotherapy and G-CSF].

To explore the dynamic change of CD34(+) cell expressing adhesion molecules in bone marrow and peripheral blood during mobilization with combination of chemotherapy and G-CSF and its clinical significance, mononuclear cells of bone marrow and peripheral blood from malignant hematopathy cases before and after mobilization with G-CSF were labeled by CD45-CY-Chrome, PE conjugated anti-CD34, and FITC conjugated anti-CD44, anti-CD49d, anti-CD62L and anti-CXCR4. For three-color fluorescence analysis by flow cytometry was performed on a FACScalibur. Also the relationship between the number of subpopulations in different expressions of adhesion molecules infused and the time of recovery in different blood cells after transplantation was evaluated. Results showed that a significantly lower expression of CD44(+) and CD49d(+) on CD34(+) cells in bone marrow after mobilization compared to that before mobilization, whereas great higher expression of CD44(+), CD49d(+), anti-CD62L(+) and lower of anti-CXCR4(+) in peripheral blood were observed after mobilization. No significant relations were found between expression of different adhesion molecules on CD34(+) cells infused and the time of reconstitution in blood cells after transplantation. It was concluded that this mobilizing regimen could downregulate the expressions of CD44, CD49d, CD62L, and anti-CXCR4 on CD34(+) cells in bone marrow, it may related to mobilization of CD34(+) cells from marrow to blood, and homing of blood CD34(+) cells into marrow.

Adolescent↗

PubMedDate not supplied

[Peripheral blood stem cell collection in pediatric malignancies: comparison between three mobilizing regimens].

PURPOSE: The optimal method for PBSC (peripheral blood stem cells) mobilization in pediatric patients is still unknown. The present study was conducted to evaluate the safety of apheresis procedures and to compare the efficacy of three methods of PBSC mobilization. PATIENTS AND METHODS: Our study was performed on 28 pediatric patients (in three groups) with solid tumors at onset or on relapse. In two groups we tried to mobilize PBSC administering CHT (based on Carboplatin with Etoposide in the first group and Cyclophosphamide in the second group) followed by granulocyte colony stimulating factor (G-CSF); in the third group the mobilization regimen was based on G-CSF alone. RESULTS: Forty-nine mobilizations have been performed and a median of 6.5 CD34+ cells x 10(6)/Kg were collected, with a median number of one apheresis for each patient. Using Carboplatin with G-CSF and Cyclophosphamide with G-CSF we collected respectively a median value of 6.75 and 7.3 x 10(6) CD34+ cells/kg. The mobilization method based on G-CSF alone showed to be less effective (median of 4.3 CD34+ cells x 10(6)/kg collected). CONCLUSIONS: In our experience the mobilizing regimens based on Carboplatin or Cyclophosphamide associated with G-CSF resulted both effective and better than the one based on G-CSF alone with a scanty number of apheresis procedures.

Adolescent↗

PubMed2004

Cytokines and stem cell mobilization for autologous and allogeneic transplantation.

Mobilized peripheral blood has become the preferred source of stem cells for both autologous and allogeneic transplantation, and granulocyte colony-stimulating factor is the most widely used cytokine for mobilization. However, the mechanisms of cytokine-induced peripheral blood stem cell mobilization are not completely understood. Several recent studies suggest a model in which proteases released into the bone-marrow microenvironment during cytokine treatment play a critical role in mobilization. However, the finding that progenitor mobilization is normal in certain protease-deficient mice suggests that this model may be too simplistic. Here we review recent studies that advance our understanding of the biology of stem cell mobilization. We then discuss cytokines in current use and in development for mobilization of autologous and allogeneic peripheral blood stem cells.

Animals↗

PubMed2004

[Mobilization of peripheral blood stem cells with mitoxantrone and high-dose cytarabine chemotherapy and rhG-CSF in patients with hematopoietic malignancies].

OBJECTIVE: To evaluate the efficacy of mitoxantrone combined high dose of cytarabine and recombinant human granulocyte colony-stimulating factor (MAG) regimen for mobilizing autologous peripheral blood stem cells (APBSC) in patients with hematopoietic malignancies. METHODS: From December 1995 to April 2003, 14 lymphoma and 29 acute leukemia patients were treated with high-dose cytarabine (2 g/m2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m2, days 2 and 3), followed by 300 microgram recombinant human granulocyte colony-stimulating factor per day (rhG-CSF 300 microg/d) i.e, the MAG regimen as mobilization regimen of peripheral blood stem cells. rhG-CSF was given subcutaneously when the white blood cell (WBC) count below 1.0 x 10(9)/L following the MA chemotherapy, APBSC were harvested when WBC count increased using Baxter CS3000plus or Cobe Spectra. RESULTS: Mobilization was successful in 13 of 14 lymphoma patients with MNC (3.91 +/- 2.70) x 10(8)/kg, CD34+ cells (17.79 +/- 12.90) x 10(6)/kg. Meanwhile, mobilization was successful in 24 of 29 acute leukemia patients with average of 2.13 times for apheresis. The median MNC and CD34+ cells yielded were 3.62 x 10(8)/kg and 7.37 x 10(6)/kg respectively, rhG-CSF was used for a median time of 7 days. Excepting for grade I-II gastrointestinal toxicity in 8 and infection in 14 cases, no major side effects were observed. There was no mobilization-related mortality. Minimal residual diseases became undetectable after mobilization in some patients. CONCLUSION: MAG is a safe and highly effective mobilization regimen in patients with lymphoma and acute leukemia.

Adolescent↗

PubMed1993

Mobile surgical hospital design: lessons from 5th MASH surgical packages for Operations Desert Shield/Desert Storm.

Operations Desert Shield/Desert Storm defined and tested a number of assumptions about the abilities of the Mobile Army Surgical Hospital. These assumptions involved the adequacies of mobility, both strategic and tactical, the number of hospital beds, surgical capability, and set-up time. This article reviews the characteristics, staffing, and surgical abilities of the four types of surgical packages deployed by the 5th Mobile Army Surgical Hospital in response to the changing patient care and tactical situation. These packages were the Forward Surgical Team, Forward Surgical Element, Mobile Army Surgical Hospital(-), and Mobile Army Surgical Hospital. Seven variables as they relate to hospital weight and cubic space are introduced. Mobility and surgical ability are emphasized as the first and second highest priority to consider in a proposed methodology when developing Mobile Army Surgical Hospitals.

Middle East↗

PubMed1997

Fasting-induced selective mobilization of brown adipose tissue fatty acids.

This study was conducted to determine whether there is selective mobilization of fatty acids from brown adipose tissue. Rats were fed a fish-oil diet and then fasted for 0, 7, or 10 days followed by analysis of the fatty acid content and composition of triacylglycerols (TAG) and phospholipid (PL) in interscapular brown adipose tissue (IBAT). Fatty acids were selectively lost from IBAT triacylglycerols, the mobilization following the same structural rules as those previously demonstrated for white adipose tissue. Fractional mobilization increased with unsaturation at a given chain length and tended to decrease with chain length at a given unsaturation. However, linoleic acid (18:2 n-6) was mobilized significantly less than predicted by these structural rules. In IBAT phospholipid, fatty acids were also selectively lost but there was no such relationship between the fractional mobilization of a fatty acid and its structure. The fatty acids of the n-6 series were exceptional in their behavior because they displayed below average fractional mobilization. In fact, linoleic and arachidonic acids actually increased their mass in IBAT phospholipid during the fast. It is concluded that, in IBAT, fatty acids are selectively mobilized during a fast, and that fasting-induced remodeling of the fatty acid composition leads to the selective retention of linoleate in the case of TAG and all the n-6 fatty acids in the case of PL.

Adipose Tissue, Brown↗

PubMed1998

Osteoclast-mediated bone resorption is stimulated during short-term administration of granulocyte colony-stimulating factor but is not responsible for hematopoietic progenitor cell mobilization.

The cellular and molecular mechanisms responsible for hematopoietic progenitor cell (HPC) mobilization from bone marrow (BM) into peripheral blood after administration of cytokines such as granulocyte colony-stimulating factor (G-CSF) are still unknown. In this study we show that high concentrations of soluble calcium induce the detachment of BM CD34(+) HPC adherent on fibronectin, a major component of BM extracellular matrix. Because G-CSF has been shown to induce osteoporosis in patients with congenital neutropenia and in G-CSF-overexpressing transgenic mice, we hypothesized that short-term G-CSF administration may be sufficient to induce bone resorption, resulting in the release of soluble calcium in the endosteum leading in turn to the inhibition of attachment to fibronectin and the egress of HPC from the BM. We show herein that in humans, serum osteocalcin concentration, a specific marker of bone formation, is strongly reduced after 3 days of G-CSF administration. Furthermore, in patients mobilized with G-CSF either alone or in association with stem cell factor or interleukin-3, the reduction of serum osteocalcin is significantly correlated with the number of HPC mobilized in peripheral blood. Urine levels of deoxypyridinoline (DPyr), a specific marker of bone resorption, gradually elevated during the time course of G-CSF administration until day 7 after cessation of G-CSF, showing a simultaneous stimulation of bone degradation during G-CSF-induced HPC mobilization. In an in vivo murine model, we found that the number of osteoclasts was dramatically increased paralleling the elevation of DPyr after G-CSF administration. When pamidronate, an inhibitor of osteoclast-mediated bone resorption, was administered together with G-CSF in mice, the G-CSF-induced increase of DPyr levels was completely abolished whereas the numbers of colony-forming cells mobilized in peripheral blood were not decreased, but unexpectedly increased relative to the numbers elicited by G-CSF alone. Collectively, our data therefore show that short-term administration of G-CSF induces bone degradation by a simultaneous inhibition of bone formation and an enhanced osteoclast-mediated bone resorption. This increased bone resorption is inhibited by pamidronate without reducing G-CSF-induced HPC mobilization, suggesting that the activation of bone resorption after G-CSF administration is not the direct cause of HPC mobilization as initially hypothesized, but a parallel event.

Adult↗

PubMed1998

Factors affecting the rate of iron mobilization during venesection therapy for genetic hemochromatosis.

Although progressive iron accumulation is a characteristic feature of genetic hemochromatosis, the factors affecting the rate of iron mobilization by venesection have not been established. Venesection records were analyzed in 77 hemochromatosis homozygotes to study the factors affecting the rate of iron mobilization by venesection. The rate of iron mobilization was the iron removed divided by the time required to deplete iron stores (serum ferritin < 50 microg/L). Mean duration of venesection therapy was 1.4 years (range 0.44-3.6 years). All patients completed the therapy and there were no significant adverse effects. Rate of iron mobilization was higher in cirrhotics compared to non-cirrhotic patients (P = 0.04). Iron mobilization was inversely related to intestinal radioiron absorption (r = -0.45, P = .01). There was no significant relationship between iron mobilization and patient age, gender, serum ferritin, and hepatic iron concentration. Iron mobilization is increased in cirrhotics and patients with lower intestinal iron absorption. Venesection therapy is safe and well tolerated in all age groups.

Adult↗