Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

A variant of the HL-60 cell line expressing a high level of PTP1C exhibits increased susceptibility to differentiation by phorbol 12-myristate 13-acetate

A variant of the HL-60 cell line, HL-60/MCSFR4D2, has been found to express twice the amount of PTP1C as compared to the parental HL-60 cell line by immunoblotting and immunoprecipitation. Differentiation of the variant cells after phorbol 12-myristate 13-acetate (PMA) treatment was examined by the appearance of adherence. In 1% fetal calf serum (FCS), 20% of HL-60/MCSFR4D2 cells exhibited adherence after treatment with 0.5 ng/ml PMA for 48 h, 60% exhibited adherence after treatment with 1.0 ng/ml PMA and 80% exhibited adherence after treatment with 5.0 ng/ml PMA, while HL-60 cells exhibited only a slight response. Furthermore, antisense PTP1C oligonucleotides decreased the PMA-induced adherence of HL-60/MCSFR4D2 cells. These results suggest that the high-expression of PTP1C in HL-60 cells may be involved in the enhancement of susceptibility to macrophage-like differentiation by PMA.     

pp60c-src encoded by the proto-oncogene c-src is a product of sensory neurons

The advent of recombinant DNA technology has led to the identification in the DNA of normal animal cells of over 30 proto-oncogenes that are homologous to retroviral transforming genes. One of these encodes a protein kinase (pp60c-src) of unknown function, that is preferentially synthesized in brain and neural retina. Here the expression of pp60c-src in the peripheral nervous system was examined in sensory neurons from chick dorsal root ganglia with antisera raised against the transforming protein of Rous sarcoma virus (pp60v-src) expressed in Escherichia coli carrying the cloned v-src gene. This antiserum recognizes pp60c-src specifically in normal chicken cells. Western immunoblotting showed that dorsal root ganglia of stage 30 (day 6.5) chick embryos contained elevated levels of pp60c-src. Immunoperoxidase staining of neuron-enriched cultures prepared from chick dorsal root ganglia showed pp60c-src immunoreactivity in cells with neuronal morphology; flat, fibroblastic cells contained no detectable immunoreactivity. Indirect double immunofluorescence with pp60src antibodies and monoclonal antibodies against the 200-kD subunit of neurofilament protein confirmed that the cells expressing pp60c-src were neurons. Ninety-six percent of the neurofilament-positive cells were immunoreactive with pp60src antibodies, and conversely, all pp60c-src-positive cells were immunoreactive with neurofilament antibodies. pp60c-src immunofluorescence appeared to be distributed over the cell body, processes, and growth cones. These results clearly demonstrate that pp60c-src is a product of neurons and is expressed in sensory neurons in culture.     

HL－60和抗分化HL－60细胞的基本生物学和细胞遗传学特征比较

对本实验室克隆的人急性早幼粒白血病细胞株ＨＬ－６０及其抗维甲酸分化亚系ＨＬ－６０／ＲＡ进行细胞增殖、细胞周期、分裂中期细胞染色体分布和Ｇ－显带核型分析。发现两者在倍增时间和细胞形态上基本一致。在细胞周期分布上，两者都具有肿瘤细胞的周期分布特征，但ＨＬ－６０／ＲＡ细胞的Ｓ期细胞群少于ＨＬ－６０细胞。两者染色体数量分布比较集中，染色体众数分别为４５±３（ＨＬ－６０）和４５±１（ＨＬ－６０／ＲＡ），呈近二倍体核型，Ｇ－显带核型分析表明两者都接近正常二倍体核型，都含较多的异常染色体。上述结果说明ＨＬ－６０和ＨＬ－６０／ＲＡ细胞的遗传学来源一致。     

中药安迪对HL-60细胞分化的诱导作用

目的　探讨安迪粉针剂 (Andi)对 HL- 60细胞分化的诱导作用 .方法　采用人早幼粒白血病细胞株 (HL - 60 )为靶细胞 ,分为不加任何药物的对照组 (C组 )、安迪粉针剂 (Andi)组、阳性对照药维甲酸 (RA)组和苦参 (KS)组 ,进行体外培养和诱导分化 ,观测细胞生长曲线、细胞形态、硝基蓝四氮唑(NBT)还原和吞噬能力等指标 .结果　 2 mg· L-1 Andi可显著地抑制 HL - 60细胞增殖 ,使原始细胞分化为中幼以下的成熟细胞 ,分化后的细胞具有 NBT还原能力和吞噬功能 ;Andi为 68.0 % ,RA为 61 .5% ,KS为 59.0 % ,C组还原能力仅6.0 % (P<0 .0 1 vs C) .其形态的改变和吞噬能力与阳性对照药维甲酸 (RA)和苦参 (KS)相似 ,分别为 52 .0 % ,45.5%和56.5% (P>0 .0 5) ;均明显高于空白对照组 .C组吞噬功能仅7.5% (P <0 .0 1 vs C)其 NBT还原能力与 KS相当 (P >0 .0 5) .结论　 Andi对 HL - 60细胞具有显著的诱导分化作用     

60Coγ射线辐照神经移植后神经传导速度观察

目的 探讨变性神经移植后神经传导速度情况. 方法 将30只大鼠分为实验组、对照组和正常组,实验组将60Coγ射线先期辐射处理后的兔自体神经原位再植,对照组切除后不经辐射直接自体再植,正常组不做任何处理.再植术后4月、6月和8月分别对3组大鼠行电生理检查,观察神经传导速度. 结果术后4月实验组的神经传导速度[(47.047±1.203)m/s]与正常组[(92.156±6.456)m/s]、对照组[(54.717±4.139)m/s]比较差异均有统计学差异(P<0.05);而术后6月和8月实验组与正常组、对照组比较,差异无统计学意义(P>0.05). 结论 长段自体神经(约3cm)经60Coγ射线先期处理后再植,神经传导速度可逐渐恢复正常.     

氮芥抗药性人早幼粒白血病HL60细胞亚系的建立及其生物特性

用逐步递增药物浓度和软琼脂细胞克隆技术，药物连续作用１４个月后获得氮芥（ＨＮ２）抗药性人早幼粒白血病ＨＬ６０细胞亚系，抗件达５～７倍（ＨＬ６０／ＮＨ２６），在无ＨＮ２培养液中５倍以上抗性维持１０个月以上，抗性细胞亚系的生物学特性除倍增时间稍长和克隆形成率略低外其生长曲线，细胞周期细胞ＤＮＡ指数，形态学，组织化学和染色体分析均与亲代细胞相似。     

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

蝌蚪提取液诱导人早幼粒白血病细胞分化的实验研究

目的 :探讨蝌蝌提取液 (T871)对白血病细胞的诱导分化作用。方法 :利用细胞生长曲线、形态学观察、细胞免疫化学及原位mRNA杂交和完整细胞原位斑点印迹技术 ,观察了T871诱导HL 60细胞分化的作用和分化过程中癌基因c myc、c myb表达的变化。结果 :T871能抑制HL 60细胞的增殖 ,形态学表现为类似单核 /巨噬细胞 ,同时T871还能使HL 60细胞的NBT还原能力、ANAE活性显著增强 ,同时伴有癌基因c myc、c mybmRNA表达的下调。结论 :T871能诱导HL 60细胞向单核 /巨噬细胞方向分化 ,c myc、c myb癌基因可能参与了此过程