Estrogen Activation of G-Protein–Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes

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多普勒超声诊断移植肾排斥反应与病理检查及肾功能指标的对比分析

目的：以病理活检结果为金标准，评估多普勒超声检查对移植肾排斥反应的诊断价值。方法：选择2003—01/2006—12在中国医科大学附属第一医院器官移植科行肾移植并在术后行超声检查的患者176例，均知情同意。①实验分组：根据术后移植肾功能分为2组，移植肾功能不良组78例，其中30例次行病理活检；移植肾功能正常组98例。②实验方法及评估：对患者移植肾行多普勒超声检查，参数选择峰收缩期流速、平均舒张期流速、阻力指数及血管显示率。血管显示率的评估标准（0～5级）：0级为肾动脉及其远侧血管未显示；5级为肾各级血管均显示良好。以病理活检结果为金标准，分别选取阻力指数=0．7，0．75，0．8，0．85为诊断界值进行诊断试验。结果：169例患者进入结果分析，脱落7例。①峰收缩期流速、平均舒张期流速不呈正态分布，无法作为肾功能评价指标。30例次病理活检中共有28例次被确诊为排斥反应，急性排斥反应15例次，慢性排斥反应13例次。②肾功能正常组患者中血管显示率5级者占63．30％，4级者占36．73％。肾功能不良组患者中血管显示率4级者占41．03％，3级者占46．15％，2级者占10．30％，1级者占2．60％。③移植肾功能不良组患者阻力指数显著高于移植肾功能正常组（P〈0．01）。移植肾功能不良组患者移植肾功能恢复后阻力指数显著低于移植肾尚未恢复时（P〈0．01），其中99％以上的患者△（阻力指数）≥0.20。④界值阻力指数=0．75的诊断试验的敏感性、特异性和准确性最高，均达到100％。结论：当移植肾血管阻力指数升高至0．75以上，特别是同一患者自身对照升高超过0.2以上和或血管显示率低于4级，结合临床表现和生化结果，提示可能出现移植肾排斥反应。     

急性心肌梗死后外周血单个核细胞表面CD147与基质金属蛋白酶-9 mRNA表达的相关性

目的：基质金属蛋白酶在急性心肌梗死后的心室重构中起着重要作用，但其调节机制目前尚未明确。实验拟通过动物模型的建立及体外细胞培养，观察急性心肌梗死后单个核细胞表面CD147与心肌成纤维细胞基质金属蛋白酶-9 mRNA表达的关系。 方法：实验于2006—08／2007-06在河北省人民医院临床实验中心完成。实验材料：SD大鼠及SD仔鼠（出生1～3d）购自河北医科大学试验动物中心。实验过程中对动物处置符合动物伦理学标准。实验方法：①将30只大鼠随机分为急性心肌梗死组（n=15）和假手术组（n=15），假手术组只过线不结扎。流式细胞分析法检测大鼠术后24h外周血单个核细胞表面CD147表达。②选择SD仔鼠制备心肌成纤维细胞。将单个核细胞与心肌成纤维细胞以细胞数0．5：1，1：1，2：1混合培养24h后，半定量反转录一聚合酶联反应法检测基质金属蛋白酶-9 mRNA表达。当单核细胞与心肌成纤维细胞2：1混合时，加入CD147单克隆抗体1，2，4μL/L，培养24h后检测基质金属蛋白酶-9 mRNA表达。 结果：①急性心肌梗死后外周血单个核细胞表面CD147表达明显增加。②单个核细胞与心肌成纤维细胞混合培养，随着单个核细胞比例的增加，心肌成纤维细胞基质金属蛋白酶-9 mRNA表达增加。③在单个核细胞与心肌成纤维细胞2：1混合培养体系中，随着加入CD147单克隆抗体浓度的增加，基质金属蛋白酶-9 mRNA生成减少。 结论：急性心肌梗死后单个核细胞表面CD147表达明显增加，对心肌成纤维细胞基质金属蛋白酶-9生成起上游调节作用。     

Blastomycosis in a young African man presenting with a pleural effusion

Blastomyces dermatitidis is a dimorphic fungus endemic to northwestern Ontario, Manitoba and some parts of the United States. The fungus is also endemic to parts of Africa. Pulmonary and extrapulmonary findings of a 24-year-old African man who presented with weight loss, dry cough and chronic pneumonia not resolving with antibiotic treatment are presented. The unusual occurrence of pulmonary blastomycosis associated with skin lesions and a moderate pleural effusion is reported.     

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS- sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811

The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL.