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排序方式: 共有578条查询结果,搜索用时 15 毫秒
121.
A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy 总被引:22,自引:2,他引:20
Gordon MS; McCaskill-Stevens WJ; Battiato LA; Loewy J; Loesch D; Breeden E; Hoffman R; Beach KJ; Kuca B; Kaye J; Sledge GW Jr 《Blood》1996,87(9):3615-3624
We performed a phase I trial of recombinant human interleukin-11 (rhIL- 11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model. 相似文献
122.
Martin Rosentritt Stefan Ries Carola Kolbeck Maria Westphal Ernst-Jürgen Richter Gerhard Handel 《Clinical oral investigations》2009,13(4):453-457
Resin-bonded fixed partial dentures (RBFPD) are used as a minimal invasive, tooth-preventing alternative for replacing anterior
teeth. Zirconia cantilever restorations were supposed to show sufficient strength for a clinical application. The aim of this
investigation was to determine the fracture characteristics of cantilever and two-retainer RBFPD, which are fabricated by
computer-manufactured high-strength zirconia. Human incisors and canines were used to form three groups of 14 RBFPDs with
different types of preparation: group 1, an invasive cantilever; group 2, a minimal-invasive cantilever and group 3, a two-retainer
RBFPD control. After thermal cycling and mechanical loading, which was performed to simulate oral service, all restorations
were loaded to fracture in a universal testing machine. One half of the specimens were investigated as a control without simulated
service. Mode of failure was determined for the three designs. Both cantilever groups showed comparable fracture resistance
of 227 N (no. 1) and 210 N (no. 2) before thermal cycling and mechanical loading. The resistance after aging was reduced to
210 N for the invasive cantilever RBFPD and to 179 N for the minimal invasive group. Three-unit RBFPDs showed a significantly
higher (p < 0.02) fracture resistance than cantilever bridges before (426 N) as well as after aging (360 N). Predominant failure was
FPD and retainer fracture for the invasive cantilever design, debonding for the minimal cantilever design and RBFPD fracture
for the two-retainer design. The present study revealed a significantly higher fracture resistance for two-retainer RBFPDs
than for cantilever RBFPDs. The frequency of adhesive debonding increased for non-retentive prepared cantilever RBFPDs. 相似文献
123.
124.
M. J. Raschke S. F. Kolbeck M. Dahne T. Lindner Kirsten Raun H. Bail 《Der Chirurg》2000,5(2):1009-1015
Das Ziel der vorliegenden Untersuchung war es zu überprüfen, ob systemisch appliziertes spezies-spezifisches rekombinantes
Wachstumshormon (GH) die Knochenheilung stimulieren kann. Hierfür wurde die linke Tibia von 30 Yucatan Minischweinen osteotomiert,
über einen Halbringfixateur stabilisiert und 2 mm/Tag für 10 Tage distrahiert. Daran schlo? sich eine 10t?gige Konsolidierungsphase
an. Die eine H?lfte der Tiere erhielt t?glich subcutan rekombinantes porcines Wachstumshormon (r-pGH) 100 μg/kg KG, die andere
H?lfte NaCl als Placebo injiziert. Mittels einer eigens entwickelten Me?vorrichtung konnte in-vivo im Zeitverlauf wiederholt
die torsionale Steifigkeit der Regenerate bestimmt werden. Nach T?tung der Tiere wurde von den distrahierten Tibiae und den
jeweiligen gesunden kontralateralen Tibiae die torsionale Bruchkraft in einer Materialprüfmaschine ermittelt. Um die endokrine
Antwort der r-pGH-Applikation zu überprüfen, wurden die Serumspiegel von Insulin-like growth factor I (IGF-I) bestimmt. W?hrend
der gesamten Konsolidierungsphase zeigte die Versuchsgruppe signifikant h?here in-vivo Steifigkeitswerte als die Kontrollgruppe.
Dabei lagen die Unterschiede zwischen 61 % (Tag 1), 101 % (Tag 4) und 81 % am Versuchsende (Tag 10 der Konsolidierungsphase).
Die postmortale torsionale Bruchkraft im Vergleich zur gesunden kontralateralen Seite wies 64 ± 22,4 % in der hormonbehandelten
Gruppe im Gegensatz zu 26 ± 12,9 % in der Kontrollgruppe auf. Die IGF-I Serumspiegel waren in der behandelten Gruppe um mehr
als das 4 fache erh?ht, w?hrend in der Kontrollgruppe keine signifikante Ver?nderung zu sehen war. Unsere Ergebnisse zeigen,
da? die systemische Gabe von r-pGH eine starke Beschleunigung der Regeneratkonsolidierung bei der Callusdistraktion am Minischwein
bewirkt. Diese knochenanabole Wirkung von GH k?nnte in der Zukunft eine Behandlungsoption bei der Distraktionsosteogenese
darstellen und dazu beitragen, die Behandlungsdauer zu Gunsten des Patienten zu verkürzen. 相似文献
125.
126.
Platelets deficient in glycoprotein IIIb aggregate normally to collagens type I and III but not to collagen type V 总被引:2,自引:1,他引:2
Kehrel B; Kronenberg A; Rauterberg J; Niesing-Bresch D; Niehues U; Kardoeus J; Schwippert B; Tschope D; van de Loo J; Clemetson KJ 《Blood》1993,82(11):3364-3370
The aggregation of platelets induced by collagens is considered an important step in primary hemostasis. Glycoprotein (GP) IIIb (GPIIIb, GPIV, CD36) has been proposed as a blood platelet receptor for collagen. Platelets from three healthy blood donors were shown to be clearly deficient in GPIIIb. These platelets aggregated normally in response to type I and III collagens. In addition, platelet factor 4, beta-thromboglobulin, and adenosine triphosphate (ATP) secretion in response to type I and III collagens was normal. The findings indicate that GPIIIb is not the major, essential collagen receptor for type I and III collagens. This would explain why all individuals with GPIIIb- deficient platelets examined so far are healthy and, in particular, show no apparent evidence of hemostatic problems. However, in contrast to control platelets, no aggregation and impaired platelet factor 4, beta-thromboglobulin, and ATP secretion was observed in response to type V collagen. Therefore, it is postulated that for type V collagen- induced aggregation both GPIa/IIa and GPIIIb are essential. 相似文献
127.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors (GMR) are expressed on myeloid cells throughout their maturational sequence. During myelopoiesis, GM-CSF induces the proliferation of precursors and has multiple effects on more mature cells; such effects include induction of maturation and priming for subsequent stimulation. GMR is expressed on a range of other cell types including acute leukemic blasts of myeloid and lymphoid lineage, but has been little studied on more mature lymphoid cells. Using sensitive triple-layer immunophenotypic techniques, we show here that both the alpha and beta c chains of the GMR are expressed on hairy cells (HCs) and myelomatous plasma cells (PCs), but not on chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) lymphocytes. The receptor was demonstrable on normal PCs in tonsil, but not on either activated or resting tonsillar B cells or on circulating normal B lymphocytes. The expression of the receptor is therefore stage specific, rather than a feature of activation. Perhaps, surprisingly, in view of its effects on myeloid cells, GM-CSF did not stimulate the proliferation or differentiation of HCs and did not protect them from apoptosis. However, the cytokine had a profound effect on the interaction of the HC with its environment. Thus, the cytokine caused a major cytoskeletal reorganization resulting in the inhibition of motility and loss of adhesion to cellular and matrix ligands. These studies indicate the importance of GM-CSF outside myelopoiesis and demonstrate a previously unrecognized stage specific role for the cytokine in B-cell biology. Taken together with our previous report that M-CSF enhances B-cell motility, the present findings indicate that myeloid growth factors act in concert to facilitate the controlled migration of certain B cells into and within tissues. 相似文献
128.
Mapping of monoclonal antibodies to human factor IX 总被引:2,自引:1,他引:2
Frazier D; Smith KJ; Cheung WF; Ware J; Lin SW; Thompson AR; Reisner H; Bajaj SP; Stafford DW 《Blood》1989,74(3):971-977
We used recombinant DNA techniques to map a panel of six monoclonal antibodies (MoAbs) to regions of the human factor IX molecule. A-2 maps to 17 amino acids at the amino terminus of the heavy chain of IXa; 2D5, an inhibitor of clotting, is defined to 36 amino acids of the first EGF- like domain of human factor IX. A-4, A-5, C10D, and FXC008 all map to a region of the heavy chain containing amino acids 180 through 310, suggesting an immunodominant site. FXC008 has been reported to interfere with binding of factor IXa to factor VIII:Ca. 相似文献
129.
Scandella D; Gilbert GE; Shima M; Nakai H; Eagleson C; Felch M; Prescott R; Rajalakshmi KJ; Hoyer LW; Saenko E 《Blood》1995,86(5):1811-1819
The finding that human factor VIII (fVIII) inhibitor antibodies with C2 domain epitopes interfere with the binding of fVIII to phosphatidylserine (PS) suggested that this is the mechanism by which they inactivate fVIII. We constructed a recombinant C2 domain polypeptide and demonstrated that it bound to all six human inhibitors with fVIII light chain specificity. Thus, some antibodies within the polyclonal anti-light chain population require only amino acids within C2 for binding. Recombinant C2 also partially or completely neutralized the inhibitor titer of these plasmas, demonstrating that anti-C2 antibodies inhibit fVIII activity. Immunoblotting of a series of C2 deletion polypeptides, expressed in Escherichia coli, with inhibitor plasmas showed that the epitopes for human inhibitors consist of a common core of amino acid residues 2248 through 2312 with differing extensions for individual inhibitors. The epitope of inhibitory monoclonal antibody (MoAb) ESH8 was localized to residues 2248 through 2285. Three human antibodies and anti-C2 MoAb NMC-VIII/5 bound to a synthetic peptide consisting of amino acids 2303 through 2332, a PS- binding site, but MoAb ESH8 did not. These antibodies also inhibited the binding of fVIII to synthetic phospholipid membranes of PS and phosphatidylcholine, confirming that the blocked epitopes contribute to membrane binding as well as binding to PS. In contrast, MoAb ESH8 did not inhibit binding. As the maximal function of activated fVIII in the intrinsic factor Xase complex requires its binding to a phospholipid membrane, we propose that fVIII inhibition by anti-C2 antibodies is related to the overlap of their epitopes with the PS-binding site. MoAb ESH8 did not inhibit fVIII binding to PS-containing membranes, suggesting the existence of a second mechanism of fVIII inhibition by anti-C2 antibodies. 相似文献
130.
Beer JH; Rabaglio M; Berchtold P; von Felten A; Clemetson KJ; Tsakiris DA; Kehrel B; Brandenberger S 《Blood》1993,82(3):820-829
To evaluate the physiologic importance of the different collagen receptors on platelets, we screened 806 patients admitted to the hospital because of hemorrhagic diathesis for eventual laboratory evidence of a pathologic platelet collagen interaction, and found 5 patients with an isolated deficiency in collagen-induced platelet aggregation. Four of these five patients had a partial defect, one had a complete defect. The structural and functional analysis of the platelets from the patient with a complete defect showed a deficiency in glycoprotein (GP) IV and autoantibodies against GPIIb/IIIa, GPIa/IIa, and GPIV. Patient plasma had only a minimal effect on normal control platelets and Naka-negative platelets. The analyses of the defect in the patient and of the data in the literature suggest that a single defect may not result in clinical bleeding (GPIV-deficient patients do not bleed), but may become symptomatic in combination with another defect such as the autoantibodies against GPIa/IIa, GPIV, and/or GPIIb/IIIa, all of which are involved in platelet collagen interactions (three of four of our immune thrombocytopenic purpura patients with anti-GPIV and anti-GPIIb/IIIa autoantibodies had a bleeding disorder). We hypothesize that it is the synergism of two abnormalities that results in the defective function, a mechanism that is in agreement with earlier studies on platelet collagen interaction that suggests that a double defect in platelet collagen interactions is required to become clinically apparent. 相似文献