WT1基因在白血病中的表达及临床意义

目的　探讨WT1基因在白血病中的作用。方法　用定量RT -PCR方法检测病人外周血或骨髓单个核细胞WT1mRNA表达。结果　 5 0例白血病患者中 ,41例WT1mRNA表达增高 ,阳性率为 82 0 %。急性髓细胞白血病 (AML)和急性淋巴细胞白血病 (ALL)阳性率分别为 84 0 %和 93 8% ,两组无显著差异 (P >0 0 5 ) ,慢性粒细胞白血病 (CML)的WT1mRNA阳性率为 6 6 7% ,其中慢性期均阴性 ,加速期和急变期均阳性。 17例完全缓解患者中 ,15例 (85 2 % )WT1mRNA转阴 ,复发患者WT1mRNA再次升高。结论　WT1mRNA表达的测定对白血病微小残留病检测具有重要意义     

慢性髓系白血病病期演变时CD34抗原表达及其临床意义

目的 检测ＣＤ３４抗原在慢性髓系白血病（ＣＭＬ）不同病期中的表达,并探讨其与临床化疗疗效及预后的关系。方法 采用流式细胞术检测ＣＭＬ患者外周血和（或）骨髓单个核细胞（ＭＮＣ）ＣＤ３４抗原及Ｐ１７０糖蛋白的表达。结果 ＣＭＬ慢性期、加速期、急变期外周血ＭＮＣＣＤ３４抗原阳性率比较差异有非常显著性（Ｐ〈０．００１）。随着治疗的有效ＣＤ３４阳性率下降;Ｐ１７０阴性组与Ｐ１７０阳性组ＣＤ３４阳性率比较差异     

髓系白血病中EVI1基因的表达及其临床意义

目的研究EVI1基因在成人急性髓系白血病(AML)和慢性粒细胞白血病(CML)中的表达及其临床意义。方法采用多重逆转录-聚合酶链反应(多重RT-PCR)技术分析2002年9月至2005年3月华中科技大学同济医学院附属同济医院收治的45例AML和43例CML骨髓单个核细胞中EVI1基因mRNA的表达,分析EVI1mRNA阳性白血病患者的临床特征及疗效。结果45例AML患者中有8例(17.8%)EVI1阳性,其中M11例、M23例、M54例。43例CML患者中有8例(18.6%)EVI1阳性,其中慢性期2例,占5.7%(2/35),加速期与急变期各3例,均占75.0%(3/4),加速期与急变期组的EVI1基因表达率高于慢性期组(P<0.01)。EVI1阳性的AML患者早期病死率高;EVI1基因阳性表达与CML白血病临床分期及预后相关。结论EVI1基因的高表达在髓系白血病的发生中,特别是在慢性粒细胞白血病慢性期向急性期转化中起重要作用。     

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慢性粒细胞白血病(CML)是具有特征性细胞遗传学改变(Ph染色体)和分子生物学特征(BCR-ABL表达)的干细胞克隆性疾病,临床主要表现为白细胞升高、外周血细胞核左移和脾肿大,分慢性期、加速期和急变期3个病期.1 造血干细胞移植治疗CML的机制     

慢性粒细胞白血病患者WT1基因表达及其临床意义

目的探讨慢性粒细胞白血病（CML）患者骨髓细胞中Wilms瘤抑癌基因（WT1）的表达水平及其临床意义。方法建立实时定量RT-PCR方法,采用Light Cycler PCR仪检测了46例（109份骨髓细胞cDNA标本）CML患者和23例非白血病患者骨髓细胞中WT1及内参β胆色原脱氢酶（GAPDH）的表达水平,以WT1N=（WT1拷贝数／GAPDH拷贝数）×10^4计算WT1表达水平。结果23份CML加速期与22份CML急变期患者骨髓细胞中WT1N的中位表达水平分别为103．71和129．44,明显高于64份CML慢性期和对照组（分别为3．44和1．47,P〈0．01）,对照组与CML慢性期之间WT1基因表达差异无统计学意义;CML加速期与急变期之间WT1基因表达差异也无统计学意义（P〈0．05）。WT1基因表达水平与BCR／ABL融合基因表达水平具有一定的相关性。对其中7例CML患者行异基因骨髓移植前后动态检测WT1上升可提示白血病复发。结论CML患者加速急变期骨髓细胞中WT1基因表达升高,具有参考意义。     

IL-3受体α在CML中的表达意义

应用半定量RT—PCR技术，对12例慢性粒细胞白血病慢性期（CML-CP组）、5例慢性粒细胞白血病急变期（CML—BP组）患者及15例正常者（对照组）行IL-3受体α（IL-3Rα）mRNA检测。结果与对照组比较，CML-CP组IL-3RαmRNA表达阳性率升高，但无统计学差异（P〉0．05）；CML-BP组明显升高（P〈0．05）。提示IL-3RαmRNA在CML—BP患者中呈高表达，与疾病分期有关。     

慢性粒细胞白血病患者sorcin基因表达及其临床意义

目的探讨慢性粒细胞白血病患者可溶性耐药相关钙结合蛋白（sorcin）基因表达与临床耐药和疗效的关系。方法应用半定量逆转录聚合酶链反应（RT—PCR）检测31例慢性粒细胞白血病（CML）患者（CML组）和27例健康人（对照组）sorcin基因表达。结果CML组sorcin基因阳性表达率明显高于对照组（P〈0．01），其急变期患者阳性率高于慢性期和加速期患者（P分别为0．03和0．18）；CML临床耐药者sorcin基因表达显著高于非临床耐药者，疗效显著低于非临床耐药者。结论CML患者sorcin基因呈高表达，与临床耐药和预后密切相关；sorcin表达可作为检测临床耐药和判断CML患者预后的指标之一。     

白血病骨髓细胞ras癌基因产物P21蛋白的免疫组化检测

用LSAB（Labelled streptavidin biotin method）免疫组化法对30例白血病骨髓细胞进行了P_（21）蛋白免疫组化检测。其中急性粒细胞性白血病（AML）14例,9例阳性,阳性率57.14%。急性淋巴细胞性白血病（ALL）11例,1例阳性,阳性率9.09%。1例慢性粒细胞性白血病（CML）为阴性。2例CML急变期（CML BP）,1例为阳性。2例慢性淋巴细胞性白血病急变期（CLL BP）均为阳性。结果显示AML的P_（21）蛋白表达率较高。将AML与ALL进行统计学分析,P=0.03,提示表达率与白血病类型有明显相关性。     

急性白血病P_(170)和CD_(34)抗原共同表达及其临床意义

目的 :探讨急性白血病 (AL ) P1 70 和 CD34 抗原共同表达与患者化疗疗效的关系。方法 :对 81例 AL患者的单个核细胞分别用抗 P1 70 单克隆抗体 UIC2 和抗 CD34 单克隆抗体标记后 ,经流式细胞仪检测后分成 4组 ,观察其与 AL 患者临床疗效的关系。结果 :P1 70 和 CD34 抗原共同高表达组的 AL 患者的临床疗效最差 ;P1 70 和 CD34 比较 ,P1 70 表达增高预后更差。结论 :P1 70 和 CD34 同时高表达临床缓解率更低 ,更有预后意义     

CIK细胞对白血病微小残留病作用的研究

目的 观察CIK细胞对自体、异体原代白血病细胞的杀伤作用,对G_0期CD34~+白血病细胞的细胞毒作用,及对正常骨髓造血干细胞的影响.方法 取急性白血病(AL)化疗后、慢性粒细胞白血病(CML)慢性期及正常人外周血单个核细胞加入一系列细胞因子诱导培养CIK细胞,流式细胞仪检测CIK表型,G带法分析CIK细胞核型.冻存、复苏后作为靶细胞,MTT法测定CIK细胞对自体、异体原代白血病细胞杀伤作用.AO染色法测定复苏后G_0期急性粒细胞白血病(AML) CD34~+细胞比例及培养后CML CD34~+细胞中G_0期细胞比例.流式细胞仪检测CIK细胞杀伤前后G_0期CD34~+细胞比例变化.半固体培养法检测CIK细胞对正常骨髓CFU-GM、BFU-E集落形成的影响.结果 CIK细胞可从白血病患者外周血中获得,来源于正常淋巴细胞,对自体原代白血病细胞有明显杀伤作用,对G_0期白血病细胞有明显抑制作用,对正常造血干细胞无杀伤作用.结论 CIK细胞可作为清除残留白血病细胞的有效工具.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.