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91.
92.
Schuening FG; Appelbaum FR; Deeg HJ; Sullivan-Pepe M; Graham TC; Hackman R; Zsebo KM; Storb R 《Blood》1993,81(1):20-26
The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone. 相似文献
93.
Heterogeneity of breakpoints of 11q23 rearrangements in hematologic malignancies identified with fluorescence in situ hybridization 总被引:3,自引:0,他引:3
Kobayashi H; Espinosa R d; Thirman MJ; Gill HJ; Fernald AA; Diaz MO; Le Beau MM; Rowley JD 《Blood》1993,82(2):547-551
Twenty-four patients whose cells contained a variety of 11q23 rearrangements, including translocations, insertions, and an inversion, were studied using fluorescence in situ hybridization with cosmid, phage, and plasmid probes mapped to 11q22-24. In 17 patients, the breakpoints of the common 11q23 translocations involving chromosomes 4, 6, 9, and 19 as well as some uncommon translocations involving 3q23, 17q25, 10p11, and an insertion 10;11 were all located in the breakpoint cluster region of the MLL gene, regardless of age, phenotype of disease, or involvement of a third chromosome. The breakpoints in 11q23 in the other 7 patients with a t(7;11)(p15;q23), inv(11)(p11q23), t(4;11)(q23;q23), der(5)t(5;11)(q13;q23), ins(10;11)(p11;q23q24), t(11;14)(q23;q11), or t(11;18;11) (p15;q21;q23) were located either centromeric to CD3D or telomeric to THY1. Thus, although most 11q23 rearrangements, involve the same breakpoint cluster region of MLL, there is heterogeneity in the breakpoint in some of the rare rearrangements. 相似文献
94.
95.
Zhang SY; Zhu J; Chen GQ; Du XX; Lu LJ; Zhang Z; Zhong HJ; Chen HR; Wang ZY; Berger R; Lanotte M; Waxman S; Chen Z; Chen SJ 《Blood》1996,87(8):3404-3409
Acute promyelocytic leukemia (APL) is an interesting model for cancer research because of the presence of the specific PML-RARalpha fusion gene associated with the clinical response to retinoic acid differentiation therapy. To better understand and improve differentiation induction with retinoic acid, we have established a human APL-ascites model in SCID mice using the NB4 human APL cell line. NB4 (1 x 10(6) cells) were transplanted into the peritoneum (IP) of SCID mice for 1 month. NB4 ascites cells (A-NB4) appeared, which were then engrafted in SCID mice periodically for 18 passages at an interval of 3 to 4 weeks with a 100% success rate of tumor induction. The mean survival times of SCID mice transplanted with 1 x 10(6) A-NB4 cells was 21.6 +/- 2.3 days. Analysis of the biologic characteristics of ninth passage NB4 ascitic cells was performed and they were found to have the morphologic, immunologic, cytogenetic, and molecular features of cultured NB4 cells. Furthermore, A-NB4 cells were capable of differentiating when treated with all-trans retinoic acid (ATRA), as manifested by enhanced NBT reduction and CD11b expression. In vivo treatment with ATRA in SCID mice for 4 days also increased NBT reduction by A-NB4 cells. ATRA treatment significantly prolonged survival time in the group after transplantation (28.1 +/- 6.8 to 29.1 +/- 8.4 days) compared with the control (P < .001). Furthermore, treatment with adriamycin, an effective chemotherapeutic drug in APL, had a strong growth suppressive effect on A-NB4 cells. These results demonstrate that this SCID-APL (NB4 ascites cells) model is a useful preclinical system for evaluating new or known drugs in the treatment of APL. 相似文献
96.
Geometric, osmotic, and membrane mechanical properties of density- separated human red cells 总被引:7,自引:0,他引:7
Although there is evidence that the deformability of the entire red blood cell (RBC) decreases during aging, reports on changes in relevant specific properties associated with the aging process are limited and not in total agreement. The purpose of this study was to evaluate some of the factors that might contribute to this decreased deformability. Geometric, osmotic, and membrane mechanical properties of unfractionated, top ("young") and bottom ("old") RBC from 5 healthy adult donors were measured using micropipette techniques. Surface area, volume, and diameter of RBC were measured at osmolalities of 297, 254, 202, and 153 mosm/kg. Two membrane mechanical properties, surface shear modulus of elasticity (mu) and time constant (tc) of viscoelastic recovery, were studied only in isotonic media. At each of the osmolalities, volume and surface area of the bottom cells were about 25% lower than those of the top cells. Bottom cells showed smaller increases in volume with decreasing osmolality than top cells; the surface area remained constant with changing osmolality for all three groups. The surface area-to-volume ratio and the minimum cylindrical diameter of the bottom cells were essentially identical to the top cells. However, both the surface area index (actual are of RBC divided by area of a sphere of same volume) and the swelling index (maximal volume divided by actual volume) of the bottom cells were significantly lower than top RBC. The shear modules of elasticity (mu) was about 0.006 dyne/cm in all 3 RBC populations, indicating that the forces necessary to deform a portion of the membrane did not change with RBC aging. The viscoelastic time constant (tc) was 0.148 +/- 0.020 (SD) sec for the bottom RBC and 0.099 +/- 0.017 sec for the top cells. This difference indicates that shape recovery following membrane deformation is delayed in old RBC. The membrane surface viscosity (eta), calculated as the product of tc times mu was 0.95 +/- 0.22 x 10(-3) dyne-sec/cm for the bottom cells and 0.54 +/- 0.15 x 10(-3) for the top RBC. These data indicate that the relative deficit in membrane surface area and the increased membrane viscosity of old RBC may be important determinants for their decreased deformability and their eventual removal from the circulation. 相似文献
97.
AIM: To demonstrate the range of applying laser angioplasty after unsuccessful recanalization of the superficial femoral artery (SFA) with conventional interventional techniques. MATERIALS AND METHODS: In a prospective trial in 94 cases with occlusion of the SFA and formerly unsuccessful conventional percutaneous transluminal angioplasty, laser angioplasty for recanalization was applied. The average length of the SFA was 17.5 cm (range 4–36 cm). The recanalization attempt was made using the crossover technique in 78 patients, in eight patients with the antegrade technique and in another eight patients using the transpopliteal technique. The primary recanalization attempt was performed with Terumo wires (curved and straight) as well as different catheters (Multipurpose/Vertebralis/Cobra). the unsuccessful recanalization attempt the laser catheter was applied. RESULTS: The application of laser angioplasty demonstrated a successful recanalization of the SFA in 76/94 patients (80.9%). In 18 patients (19.1%) the recanalization was not possible even with percutaneous transluminal laser angioplasty (PTLA). The reason for the unsuccessful PTLA was in 10 cases due to obstructing calcified material, which was resistant to PTLA application. In four cases obstructing calcifications caused the laser catheter to be positioned in subintimal tissue, resulting in perforation occlusion of the SFA. In another four patients there was an aberrant anatomy of the SFA which resulted in a direct vessel injury after advancing the laser catheter. After a follow-up period of 12 months primary, primary-assisted and secondary patency rates were 50.0%, 65.8% and 73.7%, respectively. DISCUSSION: In primarily unsuccessful recanalization of the SFA, PTLA allows in After 80% of cases a successful recanalization of the SFA. The technical success rate and the patency rate support the application of PTLA. (Int J Cardiovasc 2000; 3: 153–160) 相似文献
98.
Cor HJ Lamers Stefan Sleijfer Sabine van Steenbergen Pascal van Elzakker Brigitte van Krimpen Corrien Groot Arnold Vulto Michael den Bakker Egbert Oosterwijk Reno Debets Jan W Gratama 《Molecular therapy》2013,21(4):904-912
Autologous T cells genetically modified to express a chimeric antibody receptor
(CAR) against carboxy-anhydrase-IX (CAIX) were administered to 12 patients with
CAIX-expressing metastatic renal cell carcinoma (RCC). Patients were treated in
three cohorts with a maximum of 10 infusions of a total of 0.2 to 2.1 ×
109 CAR T cells. CTC grade 2–4 liver enzyme disturbances
occurred at the lowest CAR T cell doses, necessitating cessation of treatment in
four out of eight patients in cohorts 1 and 2. Examination of liver biopsies
revealed CAIX expression on bile duct epithelium with infiltration of T cells,
including CAR T cells. Subsequently four patients were pre-treated with CAIX
monoclonal antibody (mAb) G250 to prevent CAR-specific toxicity and showed no
liver toxicities and indications for enhanced peripheral T cell persistence. No
clinical responses were recorded. This report shows that CAIX-targeting CAR T
cells exerted antigen-specific effects in vivo and induced liver
toxicity at the lowest dose of 0.2 × 109 T cells applied,
illustrating the potency of receptor-modified T cells. We provide in-patient
proof that the observed “on-target” toxicity is antigen-directed and
can be prevented by blocking antigenic sites in off-tumor organs and allowing
higher T cell doses. 相似文献
99.
Purpose: To review the literature concerning neurophysiological methods to assess spasticity with respect to mechanisms and methodology, and to describe the three most commonly used methods: the Hoffmann reflex (H-reflex), the Tendon reflex (T-reflex), and the Stretch Reflex (SR). Method: A systematic internet database search was performed to identify neurophysiological measurement methods of spasticity. A systematic exclusion procedure resulted in 185 included references, completed by additional informal search. For this paper, information about the H-, T- and stretch reflexes was extracted from these references. Results: Although the reflexes are basically monosynaptic, there are many supraspinal pathways which modulate the responses in terms of their amplitude and latency. As a consequence the methods are sensitive to a considerable number of experimental conditions and are characterized by a moderate reliability and sensitivity. Correlations with other (i.e. biomechanical, neurophysiological or clinical) spasticity assessment parameters are moderate to poor. Standardised and broadly accepted protocols are still largely lacking preventing an effective exchange of knowledge. Conclusions: The clinical and experimental use of the three methods is restricted due to moderate reliability and sensitivity. It is recommended to perform combined neurophysiological?-?biomechanical assessment of spasticity during active, functional movement. 相似文献
100.
C Ziebold R von Kries A Siedler HJ Schmitt 《Acta paediatrica (Oslo, Norway : 1992)》2000,89(S435):17-21
Recently published and as yet unpublished data allow a reasonable estimate of the annual burden of pneumococcal disease in Germany. At least 277000 episodes of otitis media and at least 2000 episodes of sinusitis occur in children under the age of 5 y. Pneumococcal meningitis was found in 200 children under the age of 16 y; the estimate for all age groups ranges from 450 to 1100 cases. Of approximately 150000 cases of ambulatory pneumococcal pneumonia, at least 63 000–105000 patients are hospitalized each year.
Conclusion: Further studies of pneumococcal epidemiology in Germany are needed, and continued surveillance will be necessary for a better understanding of the overall burden of pneumococcal disease in children as well as adults. 相似文献
Conclusion: Further studies of pneumococcal epidemiology in Germany are needed, and continued surveillance will be necessary for a better understanding of the overall burden of pneumococcal disease in children as well as adults. 相似文献