非肿瘤性肩关节损伤与人工肩关节置换

目的:分析假体的选择与手术操作技术对非肿瘤性肩关节损伤人工肩关节置换术治疗的影响。方法:选择2001-04/2006-10在上海长征医院、西藏军区总医院、扬州第一人民医院等进行肩关节置换术患者33例。肱骨急性近端粉碎性骨折28例:行单极人工肩关节置换术17例,双极人工肩关节置换术1例,全肩关节置换术3例。肱骨头缺血坏死2例、骨性关节炎3例,均行全肩关节置换术。术后9个月时22例患者参加随访,18个月时17例参加随访,30个月时5例参加随访。结果:33例患者均进入结果分析。①1例肱骨假体留置过长致肩关节上举运动痛、静止不痛,翻修术后缓解。其余32例完全不疼。②术后患者上举85°～130°,平均(98.7±6.0)°,外旋17°～36°,平均(30.0±5.7)°。内旋75°～101°,平均(82.5±4.8)°。③患者假体置位较好,除1例肱骨假体未完全插入髓腔,翻修后正常。④材料与组织的生物相容性能:符合美国FDA及欧洲CE标准。结论:针对患者的具体情况选用合适的人工肩关节假体,术中假体固定方法的选择以及术后外固定材料的佩戴对肩袖功能有重要影响。     

Heterotypic adherence between human B-lymphoblastic and pre-B- lymphoblastic cells and marrow stromal cells is a biphasic event: integrin very late antigen-4 alpha mediates only the early phase of the heterotypic adhesion

Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow.     

A randomized prospective comparison of chemotherapy to total body irradiation as initial treatment for the indolent lymphoproliferative diseases

One hundred eight consecutive patients with indolent lymphoproliferative diseases were stratified into chronic lymphocytic leukemia (CLL), stage III and IV well-differentiated lymphocytic lymphoma (WDLL), and stage III and IV follicular lymphoma (FL). Within each stratum, patients were prospectively and randomly assigned to receive chemotherapy with chlorambucil and prednisone (CP) or fractionated total body irradiation (TBI). Morbidity from both regimens was negligible. Complete response (CR) was defined as the resolution of organ enlargement and the return of blood count to normal. The CR rate for the entire CP group (n = 54) was 59% and that for the TBI group (n = 54), 52%; median survivals were 53 and 57 months respectively. In the 41 patients with CLL the CR rate for CP (n = 17) was 47% and that for TBI (n = 24), 50%; the median survival for CP was 48 months, and for TBI it was 51 months. In the 21 patients with WDLL the CR rate for CP (n = 15) was 53% and that for TBI (n = 6), 67%; the median survival for CP was 42 months and has not yet been reached for TBI. For the 46 patients with FL the CR rate for CP (n = 22) was 72% and that for TBI (n = 24), 50%; the median survival was 55 months, and for TBI it was 56 months. None of the differences in CR or survival are statistically significant (P greater than .05). In these indolent lymphoproliferative diseases, CP and TBI are equally effective forms of initial treatment irrespective of the end point being defined as CR or survival.     

Engraftment of bone marrow cells into normal unprepared hosts: effects of 5-fluorouracil and cell cycle status

Bone marrow from animals treated with 5-fluorouracil (5FU) competes equally with normal marrow when assessed in vivo in an irradiated mouse, but shows markedly defective engraftment when transplanted into noncytoablated hosts. Using Southern Blot analysis and a Y-chromosome specific probe, we determined the level of engraftment of male donor cells in the bone marrow, spleen, and thymus of unprepared female hosts. We have confirmed the defective engraftment of marrow harvested 6 days after 5FU (FU-6) and transplanted into unprepared hosts and shown that this defect is transient; by 35 days after 5FU (FU-35), engraftment has returned to levels seen with normal marrow. FU-6 marrow represents an actively cycling population of stem cells, and we hypothesize that the cycle status of the stem cell may relate to its capacity to engraft in the nonirradiated host. Accordingly, we have evaluated the cycle status of engrafting normal and FU-6 marrow into normal hosts using an in vivo hydroxyurea technique. We have shown that those cells engrafting from normal marrow and over 70% of the cells engrafting from FU-6 marrow were quiescent, demonstrating no killing with hydroxyurea. We have also used fluorescent in situ hybridization (FISH) analysis with a Y-chromosome probe and demonstrated that normal and post-5FU engraftment patterns in peripheral blood were similar to those seen in bone marrow, spleen, and thymus. Altogether these data indicate that cells engrafting in normal, unprepared hosts are dormant, and the defect that occurs after 5FU is concomitant with the induction of these cells to transit the cell cycle.     

Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells

The p21 RAS product has been implicated as part of the downstream signaling of certain nonreceptor tyrosine kinase oncogenes and several growth factor receptor-ligand interactions. We have reported that the chronic myelogenous leukemia oncogene p210 bcr-abl transforms a growth- factor-dependent myeloid cell line NFS/N1.H7 to interleukin-3 (IL-3) independence. In these p210 bcr-abl-transformed cells (H7 bcr-abl.A54) and in two other murine myeloid cell lines transformed to IL-3 independence by p210 bcr-abl, endogenous p21 RAS is activated as determined by an elevated ratio of associated guanosine triphosphate (GTP)/guanosine diphosphate (GDP), assayed by thin-layer chromatography of the nucleotides eluted from p21 RAS after immunoprecipitation with the Y13-259 antibody. Treatment of p210 bcr-abl-transformed cells with a specific tyrosine kinase inhibitor herbimycin A resulted in diminished tyrosine phosphorylation of p210 bcr-abl and associated proteins, without major reduction in expression of the p210 bcr-abl protein itself. Inhibition of p210 bcr-abl-dependent tyrosine phosphorylation resulted in a reduction of active p21RAS-GTP complexes in the transformed cells, in diminished expression of the nuclear early response genes c-jun and c-fos, and in lower cellular proliferation rate. To further implicate p21 RAS in these functional events downstream of p210 bcr-abl tyrosine phosphorylation, we targeted G- protein function directly by limiting the availability of GTP with the inosine monophosphate dehydrogenase inhibitor, tiazofurin (TR). In p210 bcr-abl-transformed cells treated for 4 hours with TR, in which the levels of GTP were reduced by 50%, but GDP, guanosine monophosphate, and adenosine triphosphate (ATP) were unaffected, p210 bcr-abl tyrosine phosphorylation was at control levels. However, expression of c-fos and c-jun nuclear proto-oncogenes were strongly inhibited and p21 RAS activity was downregulated. These findings show that p210 bcr-abl transduces proliferative signals, in part, through downstream activation of p21 RAS. Furthermore, p21 RAS activity is linked to pathways that regulate c-jun and c-fos expression.     

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.     

4－氨基吡啶诱发组胺释放及某些药物的拮抗作用

４－氨基吡啶（４－ＡＰ）有组胺释放作用。小鼠ｉｐ４－ＡＰ５ｍｇ·ｋｇ－１后，肺中组胺含量明显减低，血中组胺含量显著增高。钙拮抗剂硝苯啶、ＴＭＢ－８及钾通道开放剂米诺地尔均能明显抑制４－ＡＰ诱发的小鼠ＰＭＣ释放组胺。结果提示，ＭＣ可能存在钾通道，４－ＡＰ诱发ＭＣ释放组胺可能与它阻滞钾通道，从而使钙通道开放，增加Ｃａ２＋内流有关。