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Results for “Mobilization potential”

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At least 163 records · Page 9Linked to original sources
PubMed2007

Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Response to pre-transplant salvage chemotherapy remains the most important prognostic factor for outcome in refractory or relapsed Hodgkin's lymphoma. Results of a new induction regimen are reported in terms of response rates, toxicity, and stem cell mobilization. DESIGN AND METHODS: Ninety-one patients with refractory or relapsed Hodgkin's lymphoma were treated prospectively with a salvage regimen consisting of ifosfamide 2000 mg/m2 on days 1 to 4, gemcitabine 800 mg/m2 on days 1 and 4, vinorelbine 20 mg/m2 on day 1, and prednisolone 100 mg on days 1 to 4 (IGEV). RESULTS: Forty-nine patients (53.8%) achieved a complete remission and 25 (27.5%) a partial response for an overall response rate of 81.3%. In the multivariate analysis response to the last chemotherapy (p<0.0001) and involvement of > or =3 sites (p<0.049) were the most important prognostic factors for response. Adequate CD34+ cell collection was achieved in 78 out of 79 (98.7%) mobilized patients. So far, no treatment-related death has been documented. Thirteen (4.2%) and 27 (8.6%) out of 313 evaluated cycles had to be delayed or reduced, respectively, mainly because of neutropenia and thrombocytopenia. No grade 4 non-hematologic toxicity was observed, except for one episode of mucositis. INTERPRETATION AND CONCLUSIONS: The high response rate, in particular the complete remission rate, the low toxicity profile, and the very high mobilizing potential of the IGEV regimen strongly suggest that patients with relapsed/refractory Hodgkin's lymphoma may benefit from the use of this salvage induction regimen.

Adolescent↗
PubMed2026

Dynamics of Antibiotic Resistance Gene Profiles in Captive Forest Musk Deer (Moschus berezovskii) Along a Breeding Duration Gradient.

BACKGROUND: To conserve wild populations and ensure a sustainable supply of musk, China initiated the captive breeding of forest musk deer. The temporal dynamics of gut antibiotic resistance gene (ARG) profiles in captive forest musk deer along a breeding duration gradient remain poorly characterized. METHODS: In this study, we employed metagenomic sequencing to systematically characterize the profiles and potential mobility of ARGs. Samples were divided into short-term, medium-term and long-term groups according to breeding durations. RESULTS: A total of 331 ARG subtypes and 71 mobile genetic element (MGE) subtypes were annotated across all samples. ARG Shannon diversity differed overall across groups (Kruskal-Wallis, p = 0.03); Bonferroni-adjusted Dunn's test showed no significant pairwise differences. PCoA (Bray-Curtis) demonstrated distinct separation of the ST group (p = 0.002), and shared core ARG subtypes gradually increased with extended breeding years. A strong positive correlation between ARG and MGE abundances was identified (r = 0.85, p = 0.0001). In total, 63 contigs carrying co-localized ARG-MGE complexes were recovered. The ST group contained the highest proportion of such contigs. The ST group displayed tight physical ARG-MGE linkage within 1-3 kb genomic intervals. CONCLUSIONS: Our results reveal that breeding duration is associated with the gut ARG characteristics of captive forest musk deer. Short-term captivity has higher ARG-MGE co-localization, suggesting a higher possibility of mobilization.

One Health↗
PubMed2001

Hapten addition to an MHC class I-binding peptide causes substantial adjustments of the TCR structure of the responding CD8(+) T cells.

T cell responses against hapten-modified peptides play an important role in the pathogenesis of certain diseases, including contact dermatitis and allergy. However, the structural features of TCRs recognizing bulky, potentially mobile hapten groups remain poorly defined. To analyze the structural basis of TCR recognition of defined hapten-modified peptides, the immunodominant octapeptide derived from vesicular stomatitis virus nucleoprotein (VSV8) was modified with a trinitrophenyl (TNP) group at the primary TCR contact residues (position 4 or 6) and used for immunization of mice carrying either the TCR alpha- or beta-chain of a VSV8 (unmodified)/H-2K(b)-specific CTL clone as a transgene. Such mice allow independent analysis of one TCR chain by maintaining the other fixed. The TCR V gene usage of the responding T cell population was specifically altered depending upon the presence of the TNP group and its position on the peptide. The CDR3 sequences of the TNP-modified peptide-specific TCRs showed a preferential J region usage in both the CDR3alpha and beta loops, indicating that the J regions of both CDR3s are critical for recognition of TNP-modified peptides. In contrast to our previous observations showing the prime importance of CDR3beta residues encoded by D-segment or N-addition nucleotides for recognition of position 6 of unmodified VSV8, our studies of TNP-modified peptides demonstrate the importance of the Jbeta region, while the Jalpha region was crucial for recognizing both TNP-modified and unmodified peptides. These data suggest that different structural strategies are utilized by the CDR3alpha and beta loops to allow interaction with a haptenated peptide.

Animals↗
PubMed1976

[Role of intermediate products of prothrombin proteolysis by thrombin in the stimulation of the anticoagulation system of blood].

Two components - the intermediate product 1 (P-1) converting under certain conditions into thrombin, and product 2 (P-2) which possesses no such properties were isolated from the products of prothrombin proteolysis by thrombin. The intravenous injection of the P-1 to rats lengthened the blood coagulation time and plasma recalcification. The sum total fibrinolytic activity proved to increase and the fibrinogen concentration - to decrease. A sharp 5-fold rise of the nonfermentative fibrinolysis was observed. It seems that this effect of the anticoagulating and fibrinolytic potential mobilization was stimulated by the response of the second anticoagulating blood system.

Animals↗
PubMed1999

Novel approaches in myeloma therapy.

High-dose melphalan (200 mg/m2) followed by one or more autologous peripheral blood stem cell transplantations is a safe and effective treatment regimen for multiple myeloma. This treatment regimen is as effective as standard therapy for myeloma in older (>65 years) patients and in patients with renal failure. However, advanced age (>50 years), duration of prior standard therapy (> 12 months), and a low CD34 mobilization potential (<20 x 10(6)/kg) are associated with a higher incidence of cytogenetic myelodysplasia. Future efforts directed at curing multiple myeloma should incorporate the best remission induction regimens presently available and should use consolidation/maintenance treatment (eg, idiotype/dendritic cell vaccination and dexamethasone/cyclophosphamide/etoposide/cisplatin combination chemotherapy) to enhance sustained complete remission. Other options to improve the treatment of myeloma include novel adjunctive therapies that target the myeloma cell microenvironment (eg, bisphosphonates, thalidomide, other antiangiogenesis agents) and allogeneic transplantation techniques to induce a graft-versus-myeloma effect.

Animals↗
PubMed2005

[Surgical management of orthopedic problems in adult patients with cerebral palsy].

OBJECTIVES: We evaluated the results of surgical treatment for orthopedic problems in adult patients with cerebral palsy. METHODS: Nine adult patients with cerebral palsy (4 females, 5 males; mean age 22 years; range 19 to 29 years) were managed surgically to lessen pain, correct deformities and contractures, and enhance their mobilization potential. Seven patients underwent bilateral multiple-level tendinous and/or musculotendinous release procedures involving the lower extremities, of whom two patients underwent additional triple arthrodesis, and one patient underwent extension osteotomy in the knee. One patient was treated with proximal femoral and distal tibial derotation osteotomies and bilateral hamstring release for knee flexion contractures. Finally, one patient was treated with posterior fusion with instrumentation for thoracolumbar scoliosis. Before surgery, four patients were community ambulators, and one patient could walk only with the aid of bilateral crutches. Four patients with total body involvement could not walk, but they could sit without support except for one patient with scoliosis. The mean follow-up was 25 months (range 8 to 49 months). RESULTS: On final evaluations, eight patients could walk without support, and one patient who could not sit preoperatively managed to sit without support. Three patients developed bilateral, five patients developed unilateral superficial skin wounds at the back of the heels associated with cast/brace use, and deep wound infection was encountered in the patient with scoliosis. All the wounds healed with early debridements and antibiotic therapy, together with the modifications made in cast/brace applications, without the need for implant removal. CONCLUSION: Surgical treatment of orthopedic problems in adult patients with cerebral palsy is of substantial importance in enhancing their sitting and walking capacities, and in restoring their community-based relations and activities.

Adult↗
PubMed1991

Chelation in metal intoxication. XXXVI: Effect of substituted piperazine dithiocarbamates in lead-exposed rats.

Chelation is most acceptable means of managing heavy metal poisoning. Piperazine hexahydrate dithiocarbamate (PHD), N-methyl piperazine dithiocarbamate (MPD), N-3-chloro-phenyl piperazine dithiocarbamate (CPD), and N-benzyl piperazine dithiocarbamate (BPD) were investigated for their efficacies to mobilize lead and restore Pb-induced hematopoietic alterations in experimentally intoxicated rats. MPD and CPD were effective in enhancing the urinary excretion of Pb. While PHD and MPD were successful in lowering hepatic Pb, CPD, and BPD were effective in doing so from renal tissue. All the chelating agents decreased the blood level of Pb. The lowering of Pb body burden had no influence on the restoration of biochemical changes which indicates that the latter may not be directly related to the metal mobilizing potential of the chelating agents. None of the compounds caused excessive depletion of body Cu or Zn. No relationship between efficacies of the chelating agents and their structures was seen. However, MPD and CPD appeared to be promising antidotes of Pb poisoning.

Animals↗
PubMed1981

Sodium and calcium regulation and the role of the cytoskeleton in the pathogenesis of disease: a review and hypothesis.

Recent years have seen a rapid development in knowledge concerning ion regulation and the cytoskeleton and their roles in many normal and abnormal cell processes. The structure and function of the cytoskeleton plays a key part in a number of cell properties including cell shape, potential mobility of intracellular proteins including receptors, cell to cell adhesion, and many other phenomena such as secretion, phagocytosis and autophagocytosis. Although earlier studies have emphasized the roles of sodium and calcium ion modification following acute and chronic cell injury, it has not been until recently that volume regulation and sodium modification have been found to be intimately linked through mechanisms such as sodium-calcium exchange and that the interaction of these regulations are associated with the cytoskeleton and the cell membrane. Therefore, it is the purpose of this review not only to summarize the vast amount of data which has rapidly accumulated in this field, and to put it into perspective, but also to advance a hypothesis which, we hope, will eventually establish that a wide variety of pathological phenomena ranging from acute cell death to chronic processes such as neoplasia, hypertension and aging are all a common series of cellular reactions.

Animals↗
PubMed1992

Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential.

The electrophoretic mobility of liposomes containing a negatively charged derivative of phosphatidylethanolamine with a large headgroup composed of the hydrophilic polymer polyethylene glycol (PEG-PE) was determined by Doppler electrophoretic light scattering. The results show that this method is improved by the use of measurements at multiple angles to eliminate artifacts and that very small mobilities can be measured. The electrophoretic mobility of liposomes with 5 to 10 mol% PEG-PE is approximately -0.5 mu ms-1/Vcm-1 regardless of PEG-PE content compared with approximately -2 mu ms-1/Vcm-1 for similar liposomes but containing 7.5% phosphatidylglycerol (PG) instead of PEG-PE. Measurements of surface potential by distribution of an anionic fluorescent probe show that the PEG-PE imparts a negative charge identical to that by PG, consistent with the expectation of similar locations of the ionized phosphate responsible for the charge. The reduced mobility imparted by the surface bound PEG is attributed to a mechanism similar to that described for colloidal steric stabilization: hydrodynamic drag moves the hydrodynamic plane of shear, or the hydrodynamic radius, away from the charge-bearing plane, that of the phosphate moities. An extended length of approximately 50 A for the 2,000 molecular weight PEG is estimated from the reduction in electrophoretic mobility.

Biophysical Phenomena↗
PubMed1997

Electrophoretic mobility and zeta potential of lysozyme crystals.

Using free-solution capillary electrophoresis, the electrophoretic mobility of micro m-sized lysozyme crystals in their growth solution at 283 K, 1.5%(w/v) NaC1, and over a range of pH values between 3.59 and 5.70 has been measured. Under these conditions, the mobility is independent of crystal size, while the calculated zeta potential increases from +8 to +24 mV as the pH decreases. Since the pH dependence of the zeta potential mirrors the pH dependence of charge on the free molecule, as determined by acid titration, it is concluded that the charge on the crystal is a result of H(+) adsorption from solution.

Journal Article↗
PubMed2002

Porphyrin self-assembly at electrochemical interfaces: role of potential modulated surface mobility.

The self-assembly of 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (TPyP) on Au(111) electrodes was investigated. The adlayer structure was found to depend on the electrode potential. At positive potentials (>0.5V(SCE)), a disordered layer of TPyP is formed on the Au(111) electrode. STM images showed that the disordered molecules are immobile. At negative potentials (-0.2V(SCE)), however, the molecules are highly mobile and can no longer be imaged by STM, though they remain on the surface. At intermediate potentials (-0.2 to +0.2V(SCE)), the TPyP formed a highly ordered adlayer. Once the ordered adlayer is formed, it persists even after the potential is stepped to higher values (0.5-0.8 V(SCE)). These results can be explained by the role of potential modulated adsorbate-substrate interaction and surface mobility. This suggests the intriguing prospect of using electrode potential to tune surface interactions and to drive surface processes, e.g., molecular self-assembly, in electrochemical systems.

Journal Article↗
PubMed2000

Wetting-driven structure formation of a binary mixture in the presence of a mobile particle pinning potential

We investigate the pattern formation on the solid substrate of phase-separating films containing mobile wetting particles with a preferential attraction for one component of the mixtures. The presence of mobile particles under the surface-particle interaction modulation breaks the isotropy of the bulk phase-separating process, leading to the formation of orientational structure due to the interplay between phase separation and wetting particle ordering under a modulated pinning potential at the late stage. Simulations suggest that the phase-separation morphology can be changed through the adjustment of the wettable-phase-particle interaction and the surface-particle interaction. It provides some important insights into this "wetting-directed spinodal decomposition."

Journal Article↗
PubMed2005

High mobility group A2 potentiates genotoxic stress in part through the modulation of basal and DNA damage-dependent phosphatidylinositol 3-kinase-related protein kinase activation.

The high mobility group A2 (HMGA2) protein belongs to the architectural transcription factor HMGA family, playing a role in chromosomal organization and transcriptional regulation. We and others have previously reported that ectopic HMGA2 expression is associated with neoplastic transformation and anchorage-independent cell proliferation. Here, we reported a correlation between increased HMGA2 expression and enhanced chemosensitivity towards topoisomerase II inhibitor, doxorubicin, in breast cancer cells. Using cells exhibiting differential HMGA2 expression and small interfering RNA technique, we showed that HMGA2 expression modulates cellular response to the genotoxicity of DNA double-strand breaks. Notably, HMGA2 enhances doxorubicin-elicited cell cycle delay in sub-G1 and G2-M and augments cell cycle dysregulation on cotreatment of doxorubicin and caffeine. We further reported that HMGA2 induces a persistent Ser139 phosphorylation of histone 2A variant X, analogous to the activation by doxorubicin-mediated genotoxic stress. Moreover, this HMGA2-dependent enhancement of cytotoxicity is further extended to other double-strand breaks elicited by cisplatin and X-ray irradiation and is not restricted to one cell type. Together, we postulated that the enhanced cytotoxicity by double-strand breaks in HMGA2-expressing cells is mediated, at least in part, through the signaling pathway of which the physiologic function is to maintain genome integrity. These findings should contribute to a greater understanding of the role of HMGA2 in promoting tumorigenesis and conveying (chemo)sensitivity towards doxorubicin and other related double-strand breaks.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

[The effect of chlorine diffusion potential on electrophoretic mobility and erythrocyte sedimentation in diluted suspensions].

Electrophoretic activity of human erythrocytes in isotonic medium with reduced NaCl content does not depend on the outer electric field strength when pH decreases from 7.3 to 5.5. At pH approximately equal to 5.3 the measured values of electrophoretic mobility drop with decrease of the outer electric field strength starting at 600-700 V/m. Simultaneously signs of the solitary settlement of erythrocytes diluted suspensions are disturbed. Estimated values of the chlorine diffusion potential in these conditions exceed the value 70-80 mV, at which the erythrocyte membrane permeability changes. It is suggested that the observed dependency of electrophoretic mobility on the field strength is caused by ion flows through the erythrocyte membrane leading to diffusion non-equilibrium in the electrolyte layer close to the membrane.

Blood Sedimentation↗
PubMed1999

Inhibitors of myosin light chain kinase block synaptic vesicle pool mobilization during action potential firing.

During repetitive action potential firing the maintenance of synaptic transmission relies on a continued supply of synaptic vesicles for fusion with the presynaptic plasma membrane. The mechanism of transport by which vesicles are delivered to the site of fusion from a reserve pool is unknown, as are the biochemical pathways linking intracellular Ca2+ elevation with vesicle mobilization. Here, using the fluorescent tracer FM1-43 in hippocampal synaptic terminals, I show that inhibitors of myosin light chain kinase can block mobilization of the reserve pool and not the immediately releasable pool.

Action Potentials↗
PubMed1975

Sialic acid, electrophoretic mobility and transmembrane potentials of the Amphiuma red cell.

Red cells from the giant salamander Amphiuma means are shown to contain sialic acid. The amount removed by the action of neuraminidase is equal to that released by acid hydrolysis, indicating that all of the sialic acid is present on the outer surface of the plasma membrane. These cells have a negative electrophoretic mobility and 100% enzymatic removal of sialic acid results in a 40% reduction in the mobility, suggesting that either a fraction of the sialic acid carboxyl groups are unavailable to the action of external electric fields, or other negatively charged groups contribute to the surface charge. A further reduction in mobility of normal and sialic acid-free cells is caused by an increased extracellular calcium concentration. The negative groups affected by calcium are most likely to be phosphate groups, since the isoelectric point of the cells is found to lie between the pK values for H2PO-4 groups and the carboxyl groups of sialic acid. Membrane potentials of single cells, from which 80% or more of the total sialic acid had been removed, were identical to those measured in normal cells, confirming that sialic acid plays little, if any, direct role in the maintenance of membrane potentials and ionic permeabilities.

Animals↗
PubMed2006

The potential of differential mobility analysis coupled to MS for the study of very large singly and multiply charged proteins and protein complexes in the gas phase.

As previously demonstrated by the technique of gas-phase electrophoretic mobility molecular analyzer (GEMMA) introduced by Kaufman and colleagues, differential mobility analysis (DMA) of charge-reduced electrospray ions in the gas phase is a useful complement to MS for studying large proteins and their weakly bound complexes. Several limitations of GEMMA, the solutions for which have the potential to greatly improve its performance, are discussed here, including DMA resolution and transmission. A quantitative theory of charge reduction kinetics for dried multiply charged globular proteins at atmospheric pressures is also presented, showing that the charge reduction time must be carefully chosen to maximize a singly charged ion signal, while avoiding survival of contaminating multiply charged species. Because charge reduction limits the range of masses analyzable by MS, we also consider the potential of a parallel-plate DMA coupled in series to an MS for DMA-MS studies without charge reduction.

Biotechnology↗
PubMed1991

Interactions between trypanocidal drugs and membrane phospholipids. A surface pressure, surface potential and electrophoretic mobility study.

Amphiphilic diphenyl methane derivatives exhibiting both antiproliferative and trypanocidal effects were studied with respect to their interactions with phospholipids, in monolayers and bilayers. These compounds, namely (4-benzyl)-phenoxy-2 trimethylammonium ethane iodide (D1), (4-tertiobutyl)-phenoxy-2 morpholinium ethane chloride (D2), and (4-benzyl)-phenoxy-2 morpholinium ethane chloride (D3), were shown to interact with phosphatidylcholine (PC) and phosphatidylserine (PS) in monolayers, as monitored by surface pressure and surface potential measurements. The film expansion of monolayers, on 10 mM NaCl subphase at pH 7.1, was more pronounced in the presence of D2 and D3 in the subphase before spreading of the lipids than with the injection of the drugs underneath a preformed film. Apparent binding constants of 10(4) M-1 were determined for both drugs from monolayer experiments. With D2 in the presence of PS, results of monolayer compressions and electrophoretic mobility measurements indicate binding of the drug to the lipid molecules only when the molecular area was large. D3 was shown to interact with PS, both in monolayers and bilayers, with a drug-to-lipid binding constant of about 2 x 10(4)M-1, as evaluated from electrophoretic mobility measurements on PS liposomes. These results, which indicate binding of these drugs to phospholipids in the order D2 less than D3, correlate with the biological activity of the drugs, and may account for the discrepancy observed between the drug concentrations required for biological and binding activities.

Animals↗