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Possible Clinical Applications (possible + clinical_application)
Selected AbstractsImmunomodulation by mesenchymal stem cells and clinical experienceJOURNAL OF INTERNAL MEDICINE, Issue 5 2007K. Le Blanc Abstract Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders. [source] Characterisation of a P140K mutant O6 -methylguanine-DNA-methyltransferase (MGMT)-expressing transgenic mouse line with drug-selectable bone marrowTHE JOURNAL OF GENE MEDICINE, Issue 9 2006Belinda A. Kramer Abstract Background Gene transfer of the P140K mutant of O6 -methylguanine-DNA-methyltransferase (MGMT(P140K)) into hematopoietic stem cells (HSC) provides a mechanism for drug resistance and the selective expansion of gene-modified cells in vivo. Possible clinical applications for this strategy include chemoprotection to allow dose escalation of alkylating chemotherapy, or combining MGMT(P140K) expression with a therapeutic gene in the treatment of genetic diseases. Our aim is to use MGMT(P140K)-driven in vivo selection to develop allogeneic micro-transplantation protocols that rely on post-engraftment selection to overcome the requirement for highly toxic pre-transplant conditioning, and to establish and maintain predictable levels of donor/recipient chimerism. Methods Using stably transfected murine embryonic stem (ES) cells, we have generated a C57BL/6 transgenic mouse line with expression of MGMT(P140K) within the hematopoietic compartment for use as a standard source of donor HSC in such models. Functional characterisation of transgene expression was carried out in chemotherapy-treated transgenic mice and in allogeneic recipients of transgenic HSC. Results Expression of the transgene provided chemoprotection and allowed in vivo selection of MGMT(P140K)-expressing cells in transgenic mice after exposure to O6 -benzylguanine (BG) and N,N,-bis(2-chloroethyl)- N -nitrosourea (BCNU). In an allogeneic transplant experiment in which transgenic HSC were engrafted into 129 strain recipients following low intensity conditioning (Busulfan, anti-CD8, anti-CD40Ligand), MGMT(P140K)-expressing cells could be selected using chemotherapy. Conclusions This MGMT(P140K) transgenic mouse line provides a useful source of drug-selectable donor cells for the development of non-myeloablative allogeneic transplant models in which variation in transplant conditioning elements can be investigated independently of gene transfer efficiency. Copyright © 2006 John Wiley & Sons, Ltd. [source] Assessment of Elastic Properties of the Descending Thoracic Aorta By Transesophageal Echocardiography with Acoustic Quantification in Patients with a StrokeECHOCARDIOGRAPHY, Issue 8 2000Seok-Min Kang M.D. Previous studies have described the use of transesophageal echocardiography (TEE) with acoustic quantification (AQ) in assessing aortic elastic properties. We hypothesized that patients with a prior history of stroke (ST) may have a higher risk of atherosclerotic change in great vessels compared to nonstroke subjects (NST) and thus have decreased elastic properties. We assessed the elastic properties of the descending thoracic aorta (DTA) by TEE in ST patients and compared them with data in NST patients. Subjects included 31 with ST without any evidence of emboli originating from the heart (age 51 ± 10 years, M: F = 20: 11) and 25 age-matched NST (M: F= 8: 17). Patients with significant valvular heart disease including aortic and mitral regurgitation, left ventricular dysfunction (ejection fraction < 55%), and congenital heart disease were excluded. Compliance (C), distensibility (D), and stiffness index (SI) were measured using AQ and M-mode measurement at a level of the left atrium. We scored atherosclerotic risk factors (ARF) such as a history of diabetes, hypertension, smoking, hypercholesterolemia, and the presence of atheroma of DTA. There was no evidence of atheroma of DTA in NST. There were no significant differences in heart rate and systolic and diastolic blood pressure between ST and NST patients. Fractional area change (FAC) of DTA was significantly lower in ST than in NST patients (3.2 ± 1.6 vs 5.4 ± 2.5%, P= 0.000). ST patients had significantly lower C (1.2 ± 0.4 vs 1.5 ± 0.7 times 10 -3 cm2 mmHg -1, P= 0.039), lower D (0.8 ± 0.3 vs 1.5 ± 0.8 times 10 -3 mmHg -1, P= 0.000), and higher SI (10.3 ± 8.8 vs 5.3 ± 2.9, P= 0.006) than NST patients. ST patients without atheroma of DTA (n± 21) also had significantly lower C (1.1 ± 0.4 vs 1.5 ±0.7 times 10 -3 cm -2 mmHg -1, P= 0.038) and lower D (3.5 ± 1.4 vs 4.8 ± 2.4 times 10 -3 mmHg -1, P= 0.021) than NST patients. There was a significant positive correlation between SI and the score of ARF (r= 0.51, P= 0.000). The regional elastic properties of DTA measured by TEE with AQ and M-mode method were abnormal in ST. Therefore, TEE with AQ technique may have a possible clinical application for the detection of early atherosclerotic changes such as alteration of elastic properties in morphological normal DTA. [source] Detection of new amino acid markers of liver trauma by proton nuclear magnetic resonance spectroscopyLIVER INTERNATIONAL, Issue 6 2006Priyadarshi Ranjan Abstract: Objective: We examined serum in patients of liver injury to explore the possible clinical application of abnormal micrometabolites as a marker of liver injury and severity in cases of traumatic liver damage. Methods: Serum were screened by proton nuclear magnetic resonance spectroscopy in 96 patients with varying degree of liver injury and compared with concentrations in healthy control volunteers. Results: Large quantities of phenylalanine and tyrosine were detected by spectroscopic analysis in patients with liver injury but not in those without liver injury (P<0.001). Proton nuclear magnetic resonance spectroscopy revealed two unique amino acids, phenylalanine and tyrosine, in the sera of the subjects with liver injury, irrespective of the extent and type of injury gauged by radiology or laparotomy. Phenylalanine spectrum was obtained in all 84 patients with liver injury (100% sensitivity) whereas tyrosine spectrum was present in 83 out of 84 patients (98.8% sensitivity) suggesting that these amino acids were specifically released in the patients of liver injury. Significant correlations were observed between phenylalanine and tyrosine concentrations and total bilirubin levels and albumin levels. Serum phenylalanine and tyrosine concentrations correlated well with imaging and laparotomy findings of liver injury. Conclusion: Phenylanaline and tyrosine appear to be specific and new markers of liver injury. [source] Protection of hematopoietic cells from O6 -alkylation damage by O6 -methylguanine DNA methyltransferase gene transfer: studies with different O6 -alkylating agents and retroviral backbonesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2001Michael Jansen Abstract: Overexpression of O6 -methylguanine DNA methyltransferase (MGMT) can protect hematopoietic cells from O6 -alkylation damage. To identify possible clinical applications of this technology we compared the effect of MGMT gene transfer on the hematotoxicity induced by different O6 -alkylating agents in clinical use: the chloroethylnitrosoureas ACNU, BCNU, CCNU and the tetrazine derivative temozolomide. In addition, various retroviral vectors expressing the MGMT-cDNA were investigated to identify optimal viral backbones for hematoprotection by MGMT expression. Protection from ACNU, BCNU, CCNU or temozolomide toxicity was evaluated utilizing a Moloney murine leukemia virus-based retroviral vector (N2/Zip-PGK-MGMT) to transduce primary murine bone marrow cells. Increased resistance in murine colony-forming units (CFU) was demonstrated for all four drugs. In comparison to mock-transduced controls, after transduction with N2/Zip-PGK-MGMT the IC50 for CFU increased on average 4.7-fold for ACNU, 2.5-fold for BCNU, 6.3-fold for CCNU and 1.5-fold for temozolomide. To study the effect of the retroviral backbone on hematoprotection various vectors expressing the human MGMT-cDNA from a murine embryonic sarcoma virus LTR (MSCV-MGMT) or a hybrid spleen focus-forming/murine embryonic sarcoma virus LTR (SF1-MGMT) were compared with the N2/Zip-PGK-MGMT vector. While all vectors increased resistance of transduced human CFU to ACNU, the SF1-MGMT construct was most efficient especially at high ACNU concentrations (8,12 µg/ml). Similar results were obtained for protection of murine high-proliferative-potential colony-forming cells. These data may help to optimize treatment design and retroviral constructs in future clinical studies aiming at hematoprotection by MGMT gene transfer. [source] Development and clinical application of nucleated red blood cell counting and staging on the automated haematology analyser XE-2100TMINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2003F.-S. Wang Summary We initially developed a new flow cytometric (FCM) reference method for the enumeration and staging of nucleated red blood cells (NRBC) in 1997 [Wang et al., 1998 (XIth International Symposium on Technological Innovations in Laboratory Haematology, Banff, Canada, 1998); Tsuji et al., 1999 (Cytometry, 1999)]. The method used CD45 antibody and propidium iodide staining to separate NRBCs from other cells. Accuracy and precision were enhanced because larger numbers of cells were counted than was possible with the manual method. We also developed a method for automated NRBC counting on a haematology analyser, the XE-2100 (Wang, 1988). NRBC were separated from other cells using a special lysing buffer and a fluorescent dye. The XE-2100 was found to detect peripheral and cord blood NRBC accurately and precisely when compared with cell morphology or FCM control methods. The FCM NRBC staging method was established through the identification of different NRBC populations following the novel staining and lysing method. To evaluate the method further, we sorted samples containing NRBCs using a FACSort and investigated NRBC staging on the Sysmex XE-2100TM based on the cell sorting results. Data were analysed using special software (ida). First, we used the data in various parameter combinations. We then established gates to classify the NRBC populations. Finally, we analysed blood specimens from patients with different types of diseases to explore possible clinical applications. [source] Measurements of functional residual capacity during intensive care treatment: the technical aspects and its possible clinical applicationsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009H. HEINZE Direct measurement of lung volume, i.e. functional residual capacity (FRC) has been recommended for monitoring during mechanical ventilation. Mostly due to technical reasons, FRC measurements have not become a routine monitoring tool, but promising techniques have been presented. We performed a literature search of studies with the key words ,functional residual capacity' or ,end expiratory lung volume' and summarize the physiology and patho-physiology of FRC measurements in ventilated patients, describe the existing techniques for bedside measurement, and provide an overview of the clinical questions that can be addressed using an FRC assessment. The wash-in or wash-out of a tracer gas in a multiple breath maneuver seems to be best applicable at bedside, and promising techniques for nitrogen or oxygen wash-in/wash-out with reasonable accuracy and repeatability have been presented. Studies in ventilated patients demonstrate that FRC can easily be measured at bedside during various clinical settings, including positive end-expiratory pressure optimization, endotracheal suctioning, prone position, and the weaning from mechanical ventilation. Alveolar derecruitment can easily be monitored and improvements of FRC without changes of the ventilatory setting could indicate alveolar recruitment. FRC seems to be insensitive to over-inflation of already inflated alveoli. Growing evidence suggests that FRC measurements, in combination with other parameters such as arterial oxygenation and respiratory compliance, could provide important information on the pulmonary situation in critically ill patients. Further studies are needed to define the exact role of FRC in monitoring and perhaps guiding mechanical ventilation. [source] Tooth wear prevention: A quantitative and qualitative in vitro studyAUSTRALIAN DENTAL JOURNAL, Issue 1 2003JA Kaidonis Abstract Background: Management of tooth wear from grinding presents a significant clinical challenge. Acrylic nightguards are often used to protect the teeth, but many patients still grind with these appliances. This study aimed to test the effectiveness of three lubricants in reducing enamel wear by using an electro-mechanical machine under controlled conditions, with a view to undertaking a subsequent longitudinal clinical study. Methods: Sectioned tooth specimens were worn against each other under different loads and with the addition of three different lubricants: calcium fluoride (CaF) powder, olive-oil, and a combination of calcium fluoride with olive-oil in the form of a slurry. Wear rates of enamel only were quantified by weighing the specimens, and resin replicas of the worn tooth surfaces were made for examination under a scanning electron microscope. Results: All three lubricants reduced the amount of enamel wear significantly compared with wearing specimens without adding lubricants. Wear rate was influenced by the type of lubricant and the load applied. Wear rates were significantly less for olive-oil and the olive-oil/CaF slurry compared with CaF alone. The microwear detail differed between the three lubricants. Conclusions: This study has shown that enamel wear can be reduced using dry or wet lubricants between opposing teeth that are worn under controlled conditions. Further research is required to clarify their possible clinical applications. [source] Pulsed electromagnetic fields induce peripheral nerve regeneration and endplate enzymatic changesBIOELECTROMAGNETICS, Issue 1 2005J.A. De Pedro Abstract An experimental study was carried out in rats with the purpose of demonstrating the capacity of pulsed electromagnetic fields (PEMFs) to stimulate regeneration of the peripheral nervous system (PNS). Wistar and Brown Norway (BN) rats were used. Direct sciatic nerve anastomoses were performed after section or allograft interposition. Treatment groups then received 4 weeks of PEMFs. Control groups received no stimulation. The evaluation of the results was carried out by quantitative morphometric analysis, demonstrating a statistically significant increase in regeneration indices (P,<,0.05) in the stimulated groups (9000,±,5000 and 4000,±,6000) compared to the non-stimulated groups (2000,±,4000 and 700,±,200). An increase of NAD specific isocitrate dehydrogenase (IDH) activity was found along with an increase in the activity of acetyl cholinesterase at the motor plate. The present study might lead to the search for new alternatives in the stimulation of axonal regenerative processes in the PNS and other possible clinical applications. Bioelectromagnetics 26:20,27, 2005. © 2004 Wiley-Liss, Inc. [source] Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass graftsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2000Zhen Ren Aims The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. Methods IMA segments (n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 µm) for 15 min. Results KRN4884 induced less relaxation (P < 0.05) in the precontraction induced by ET-1 (72.9 ± 5.5%) than by ANG II (94.2 ± 3.2%) or NA (93.7 ± 4.1%) with lower EC50 (P < 0.05) for ANG II (,8.54 ± 0.54 log m) than that for NA (,6.14 ± 0.15 log M) or ET-1 (,6.69 ± 0.34 log m). The relaxation in the IMA pretreated with GBC was less than that in control (P < 0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05) induced by NA (151.3 ± 18.4% vs 82.7 ± 8.7%), 5-HT (82.7 ± 12.2% vs 30.1 ± 7.3%), and ANG II (24.3 ± 6.3% vs 5.4 ± 1.6%), but did not significantly reduce the contraction induced by ET-1 (P > 0.05). Conclusion KRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor-selective. [source] | |||||||||||||