1,25-Dihydroxyvitamin D3 promotes prostaglandin E1-induced differentiation of HL-60 cells

Human promyelocytic HL-60 cells can be induced by biochemical agents to differentiate in vitro towards divergent types of myelomonocytic cells. It has been reported that prostaglandin E₁ (PGE₁) can induce granulocytic differentiation and that 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) can induce monocytic differentiation. We have now examined the effects of these compounds, both alone and in combination, on HL-60 cell differentiation. PGE₁ (1 g/ml) or 1,25(OH)₂D₃ (10 nM) each inhibited cell proliferation over 48–96 hours of treatment, but combined treatment with both agents was necessary to produce a strong inhibition. The percentage of HL-60 cells that can reduce nitroblue tetrazolium (NBT) (a characteristic index of early monocytic or granulocytic differentiation) increased 13-fold within 72 hours of PGE₁ treatment, and 1,25(OH)₂D₃ produced a fivefold stimulation. However, combined treatment (PGE₁ plus 1,25(OH)₂D₃) produced a dramatic 35-fold increase. HL-60 cells did not produce significant levels of nitric oxide (NO) before 48 hours in culture, and treatment with PGE₁ or 1,25(OH)₂D₃ did not significantly increase cellular NO elaboration over control levels. However, combined treatment produced a striking 12-fold increase over control levels. Similarly, combined treatment was necessary to obtain the maximal time-dependent stimulation of cellular lactate dehydrogenase (LDH) activity (a marker of granulocytic differentiation) as well as acid phosphatase (ACP) activity. During this same period of time, PGE₁, but not 1,25(OH)₂D₃, markedly stimulated cellular claboration of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-, and 1,25(OH)₂D₃ cotreatment strongly augmented these effects. Thus, combined treatment with 1,25(OH)₂D₃ plus PGE₁ generally augmented the apparent conversion of these cells, producing synergistic (multiplicative) or additive effects. Furthermore, PGE₁ induced within 48 hours the more general phenotypic changes classically associated with the differentiation of these cells: increased expression of chloroacetate esterase (ChAE) (a granulocytic marker), decreases in the nuclear/cytoplasmic ratio (characteristic of development beyond the promyelocyte/myelocyte stage), and major alterations in morphology from floating spherical cells to loosely adherent, elliptical polygons. 1,25(OH)₂D₃ had little effect itself on most of these parameters, but augmented the morphological changes induced by PGE₁ treatment. Within 48 hours, the ability of these cells to reduce the tetrazolium salt WST-1, a general measure of cellular metabolic activity, was increased by PGE₁, but not by 1,25(OH)₂D₃; however, the combination of 1,25(OH)₂D₃ and PGE₁ again produced the strongest stimulation. Similarly, only PGE₁ significantly reduced intracellular ATP levels, but combined treatments produced a more pronounced decrease. In summary, our findings suggest that PGE₁, not 1,25(OH)₂D₃, is sufficient to promote rapid in vitro differentiation of HL-60 cells along the granulocytic pathway; however, the PGE₁-induced conversion of these cells is markedly augmented by cotreatment with 1,25(OH)₂D₃. In addition, these converted HL-60 cells preferentially utilize the glycolytic pathway, rather than the citric acid cycle, for production of ATP, a metabolic characteristic that resembles that described for mature granulocytes.     

Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives

Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and modified fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [¹²³I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are¹²³I-labelled IPPA and BMIPP. While [¹²³I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [¹²³I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [¹²³I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [¹²³I]IPPA and [¹²³I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging.     

Phase II trial of oral 1,25-dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancer

Epidemiologic and experimental data support a role for 1,25-dihydroxyvitamin D₃ in the growth regulation of prostate cancer. We conducted a phase II clinical trial evaluating calcitriol (1,25(OH)₂D₃) in patients with hormone refractory prostate cancer. We enrolled 14 patients in this study. 1,25(OH)₂D₃ was initiated at a daily oral dose of 0.5 μg and escalated to 1.5 μg daily. No objective responses were observed. However, in two patients decreases of 25% and 45% in prostate specific antigen levels were seen. Hypercalcemia was the predominant toxicity. We conclude that 1,25(OH)₂D₃ given in this manner is inactive in advanced prostate cancer. Dose escalation of oral 1,25(OH)₂D₃ is limited by hypercalcemia.     

噪声性暂时性听阈位移（TTS）及其影响因素分析

本文对某麻纺厂织袋、纺麻、梳麻车间从事噪声作业的工人,排除非噪声性致聋因素及生活噪声的影响,共检查212人424耳的纯音听力以及工作一个班次（6小时）后的暂时性所阈位移（TTS）,同时测定各车间噪声强度（A声级）,数据采用直线回归、逐步多元回归和协方差分析等统计学方法处理。结果表明：性别间和左右耳间的语频听阈及TTS均无显著性差异;车间噪声强度与语频听阈及TTS间存在着正相关;TTS与语频听阈、年龄、工龄之间存在着负相关。经多元逐步回归分析,语频听阈、噪声强度和工龄对TTS的影响具有统计学显著性意义。     

HBV不同血清学标志组合中HBV—DNA的分布特征

采用聚合酶链反应（PCR）技术对270例HBV不同血清学标志及不同组合进行了HBV-DNA的检测。揭示HBV-DNA在HBeAg标志中检出率最高,阳性率为100．00％;其次是HBsAg、抗-HBc和抗一HBe,阳性率分别为66．0％、65．9％和46．2％;在抗-HBS标志物中未能检出HBV-DNA。并示出了HBV-DNA在HBV血清学标志不同组合中的阳性率有着非常显著性差别,研究表明,在HBeAg阴性组合中,采用聚合酶链反应技术检测HBV-DNA的临床意义,同明还分析了HBV-DNA与性别、HBsAg滴度及ALT的关系。     

早孕妇女中沙眼衣原体感染及产前诊断的研究

用PCR法对100例早孕妇女的子宫颈标本和绒毛组织进行沙眼衣原体(CT)检测,结果发现:孕妇宫颈感染率为11％(11/100),绒毛感染率为7％(7/100),在11例宫颈CT阳性的孕妇中,发现有5例绒毛CT为阳性(45.5％)。同时显示无业、个体经商者、多次妊娠(>3次)、宫颈糜烂分别是孕期感染CT的高危人群和重要因素。结论:在孕期保健中,应开展CT筛查,尤其对具有高危因素的孕妇进行检查,以利于早期发现衣原体感染,及时治疗,从而提高人口素质。     

上海市徐汇区性病流行特征及其分析

的探讨徐汇区性病流行特征及其趋势。方法对徐汇区１９８９～１９９７年的性病报告资料进行分析。结果１９８９～１９９７年,徐汇区的性病流行呈现高速、持续和中速增长三个时期,１９８９～１９９１年平均增长７５．６３％;１９９２～１９９４年平均增长２１．６６％;１９９５～１９９７年平均递增５０．１８％。淋病为优势病种;１９９５年以前２０～３９岁为高发年龄段,１９９５年以后,２０～４４岁为高发年龄段;文化层次较低者发病数较多;工人和经商者发病率较高;新生儿和儿童淋病明显增多;梅毒的发病数在逐年增加,呈现出高速增长态势。结论性病防治工作的重点是加强性病防治机构建设,实行匿名就诊,加强对高危人群监测和重点行业人群的宣传教育。     

血液制品丙肝病毒与艾滋病毒检测

目的了解１９９３～１９９５年度临床使用的新鲜冰冻血浆（ＦＦＰ）和血液制品中艾滋病毒（ＨＩＶ）、丙肝病毒（ＨＣＶ）的感染情况。方法用ＥＬＩＳＡ、ＷＢ和ＰＣＲ对１１０批ＦＦＰ、人血丙种球蛋白、人血白蛋白检测了抗ＨＣＶ、ＨＣＶＲＮＡ、抗ＨＩＶ（１＋２）、ＨＩＶ－１ＲＮＡ。结果所有血制品抗ＨＣＶ的平均阳性率为１９．１％,ＨＣＶＲＮＡ为１７．３％;１９９３～１９９４年度ＦＦＰ的抗ＨＣＶＨＣＶＲＮＡ阳性率比１９９５年度高（３０％、２６％和０．５％）;人血丙球的抗ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于人血白蛋白（３０％、２０％和０．５％）;８９批抗ＨＣＶ阴性血制品ＨＣＶＲＮＡ的阳性率为５．６％,所有血制品的抗ＨＩＶ（１＋２）和ＨＩＶ－１ＲＮＡ均阴性。结论１９９３～１９９５年度临床上所使用的血制品,特别是１９９３～１９９４年度的ＦＦＰ,有传播ＨＣＶ的危险,这与当时没有对所有供血者进行抗ＨＣＶ筛检有关。     

羧乙基锗倍半氧化物对大鼠心肌缺血再灌注损伤的保护作用

目的：观察羧乙基锗倍半氧化物（ＣＧＳ）对大鼠实验性心肌缺血再灌注损伤的影响。方法：采用结扎大鼠冠状动脉３０ｍｉｎ后再通６０ｍｉｎ造成心肌缺血再灌注损伤模型,测定动脉血压,心律失常发生率,心律失常严重指数（ＡＳＩ）,心肌组织中丙二醛（ＭＤＡ）含量,超氧化物歧化酶（ＳＯＤ）及ＡＴＰａｓｅ活性,血清中乳酸脱氢酶（ＬＤＨ）的水平等指标。结果：预防性静注ＣＧＳ（５０ｍｇ／ｋｇ）可显著降低再灌注心律失常发生率,心肌组织中ＭＤＡ和血清中ＬＤＨ的水平;明显改善再灌注后动脉血压的下降,心肌组织中ＳＯＤ及ＡＴＰａｓｅ活性的降低。结论：ＣＧＳ对大鼠实验性心肌缺血再灌注损伤具有保护作用     

丙烯腈对大鼠外周血淋巴细胞DNA损伤的研究

［目的］ 探讨丙烯腈对大鼠外周血淋巴细胞ＤＮＡ的损伤作用。［方法］ 在急性和亚急性经口染毒试验中,采用单细胞凝胶电泳技术检测不同染毒剂量（１０ｍ ｇ／ｋｇ、３０ｍ ｇ／ｋｇ 和５０ｍ ｇ／ｋｇ）丙烯腈（ＡＣＮ）及不同染毒时段（２ｈ、１４ｄ、２８ｄ、和４２ｄ）对大鼠淋巴细胞ＤＮＡ 的损伤情况。［结果］ 在急性和亚急性染毒试验中,大鼠淋巴细胞ＤＮＡ损伤程度均随ＡＣＮ 染毒剂量增大或染毒时间延长而逐渐加重,并显著高于对照组或染毒１４ｄ 组（Ｐ＜０．０１）,且存在较好的剂量－反应和时间－反应关系（Ｐ＜ ０．０１）。亚急性染毒试验中,随着染毒剂量的升高和染毒时间的延长,淋巴细胞ＤＮＡ 的损伤程度可达到饱和。染毒组细胞ＤＮＡ 损伤反应模式明显不同于对照组,单个细胞间的差异较大,且这种差异随染毒剂量增大和染毒时间延长也逐渐增大。［结论］ ＡＣＮ对大鼠外周血淋巴细胞ＤＮＡ具有明显的损伤作用,且损伤程度和模式受ＡＣＮ 染毒剂量和染毒时间的共同影响。