血液肿瘤患者FLT3/ITD基因突变的检测及临床意义

目的检测血液肿瘤患者FLT3/ITD基因突变,探讨其突变的临床意义。方法2001—2005年对南方医科大学南方医院血液科332例血液肿瘤患者,采用聚合酶链反应(PCR)方法检测FLT3/ITD基因突变。结果FLT3/ITD基因突变阳性率分别为急性髓性白血病(AML)22.3%(23/103)、慢性髓性白血病急变期(CML-BC)6.5%(2/31)、骨髓增生异常综合征(MDS)5.6%(2/36)和急性淋巴细胞白血病(ALL)2.6%(2/76)。而慢性髓性白血病慢性期(CML-CP)、慢性淋巴细胞白血病(CLL)、多发性骨髓瘤(MM)和非霍奇金淋巴瘤(NHL)均未发现FLT3/ITD基因突变。FLT3/ITD基因突变阳性AML患者外周血WBC计数及骨髓白血病细胞比例显著高于FLT3/ITD基因突变阴性AML患者(P<0.05),FLT3/ITD基因突变阳性AML患者完全缓解后18个月内累计复发率(63.6%)显著高于FLT3/ITD基因突变阴性AML组(27.7%)(P<0.05)。结论FLT3/ITD基因突变检测对血液肿瘤预后有一定意义;FLT3/ITD基因突变AML患者预后差。     

抑癌基因Mxil在白血病细胞中突变的研究

目的：分析Mxil基因突变在白血病发病中的作用。方法：利用逆转录-聚合酶链反应（RT-PCR）、单链构象多态性（SSCP）分析及DNA序列分析技术检测26例初治急性白血病患者、30名健康对照者和2种髓系白血病细胞株（KG1、K562）Mxil基因表达及突变情况。结果：RT—PCR显示所有标本中均可检测到Mxil基因的表达，在11．5％（3／26）初治急性白血病患者和KG1细胞株中发现四处错义突变，发生突变的3例患者均于确诊后5个月内死亡。结论：首次在急性白血病细胞中发现Mxil基因突变，提示Mxil基因的突变可能与白血病的发病和预后有关。     

FLT3在急性髓细胞白血病中的研究进展

急性髓细胞白血病（AML）是一组具有不同生物学特性的恶性血液肿瘤。近年来,分子遗传学研究的进展使得大多数AML可以检出基因水平的异常,其中FLT3基因突变在AML发生及预后中起重要作用,并为白血病的靶向治疗提供了新的目标。本文对此作一综述。     

急性白血病p16基因微卫星不稳定性及杂和性缺失的研究

目的分析急性白血病（AL）患者p16基因连锁的微卫星不稳定性（MSI）和杂和性缺失（LOH）,了解p16基因改变与AL发生的关系。方法采用多重PCR方法检测53例AL患者骨髓及口腔黏膜细胞标本的p16基因连锁的3个微卫星位点（D9S162、D9S1748、D9S171）,观察其MSI及LOH情况。结果53例AL患者中,MSI检出率为43．4％（23／53）;位于9p21的p16基因连锁的微卫星D9S162、D9S1748、D9S171的LOH发生率分别为0（0／53）、5．7％（3／53）和9．4％（5／53）,MSI发生率分别为13．2％（7／53）、7．6％（4／53）和7．6％（4／53）。结论AL患者p16基因连锁微卫星均可检测到高频率的MSI和LOH,说明p16基因突变与AL发生、发展有关。     

复杂易位t(2;8;21)(p12;q22;q22):变异型t(8;21)急性粒细胞白血病1例报告并文献复习

目的：探讨急性髓系白血病（AML）伴有t（2;8;21）（p12;q22;q22）复杂易位的实验室和临床特点。方法：取患者骨髓液,进行形态学检查及流式细胞术检测;用逆转录聚合酶链反应（RTPcR）方法检测AML1／ETO融合基因转录本;G显带分析染色体核型。结果：患者诊断为急性粒细胞白血病部分分化型（AML-M2）,PT—PCR检测到阳性AML1／ETO融合基因,染色体核型分析有t（2;8;21）（p12;q22;q22）复杂易位。结论：变异型t（8;21）累及染色体2p12区,可能对白血病的临床表现、预后等因素产生影响,但仍需要积累更多的病例以明确其临床与预后的特点。     

大肠癌p53、K-ras基因突变研究

目的：探讨p53,K-ras基因突变与大肠癌发生、发展的关系。方法：应用PCR－SSCP方法研究68例大肠癌和癌旁组织以及20例正常组织p53,K-ras基因突变情况。结果：大肠癌组中p53，K-ras基因突变率分别为47．1％和44．1％，明显高于癌旁组（分别为13．2％和7．4％），20例正常组织中未检出p53、K-ras基因突变，大肠癌伴有淋巴结转移及远处转移，p53、K-ras基因突变率明显高于无淋巴结及远处转移；p53、K-ras基因突变与组织学分型无关。结论：p53、K-ras基因突变与大肠癌发生、发展有密切关系，在细胞癌变中起重要作用，可作为评估大肠癌转移的分子生物学指标。     

BCR／ABL基因与白血病

BCR／ABL融合基因几乎见于所有的慢性粒细胞性白血病（CML）及25％～50％的急性B系淋巴细胞性白血病（ALL）和约5％的急性粒细胞性白血病（AML）中“’。包括转染及转基因鼠在内的大量实验资料表明，BCR／ABL融合基因在上述白血病的发病中起重要作用。本文就目前的研究状况从①BCR／ABL基因的分子生物学特性；＠BCR／ABL基因引起肿瘤转化的可能机制；③BCR／ABL基因在引起复杂白血病类型中的特殊作用，对BCR／ABL基因在白血病发生发展中的作用作一综述。IBCR／ABL基因的分子生物学特性BCR／ABL基因是由9号与22号染…     

慢性髓细胞白血病急变期形态学及免疫学和细胞遗传学特征研究

目的：探讨慢性髓细胞白血病急变期（CML－BC）的形态学、免疫表型和细胞遗传学法及流式细胞仪进行细胞免疫分型,细胞遗传滂采用直接法或短期培养法制备染色体标本,采用R显带技术进行核型分析。结果：免疫分型结果显示：急变为急性髓细胞白血病（AML）23例占74．2％;急性淋巴细胞白血病（ALL）5例占16．1％,均为B系ALL,其中4例同时伴有髓系表达;急性未分化细胞白血病1例,B系和髓系急性混合细胞白血病（AMLL）2例。31例CML－BC中21例（67．7％）的急变患者CD34^ ,其中4／5（80．0％）ALL,15／23（65。2％）,2／2AMLL均为CD34^ 。AML急变患者中具有CD7和CD34共表达者为8／23（占34．8％）。细胞遗传学分析表明,14／27（51．9％）和急变期患者出现Ph染色体以外的附加核型异常,其中有＋8（3／14）,＋Ph(3/14),i(17q)(2/14),Y染色体丢失（1／14）及复杂易位5／14）。结论：CML－BC是一干细胞疾病,原始细胞分化阻滞在早期阶段,故预后差。MIC分型在CML－BC诊断,预后判断及指导治疗方面均有重要价值。     

急性白血病长期生存的预后因素

急性白血病是血液系统常见的恶性肿瘤，不治疗大多数人短期内死亡。70年代前，急性髓性白血病（AML）和急性淋巴细胞性白血病（ALL）的完全缓解（CR）率均＜50％，70年代后联合化疗的应用，使CR率提高，成人AMLCR率60／～70％，ALL的CR率80％左右；现在儿童AML的CR率70％～80％     

甘肃人群NQO1基因多态性与急性髓系白血病易感性的关系

目的：研究醌氧化还原酶（NQO1）基因多态性和急性髓系白血病易感性的关系。方法：用1：1配对病例-对照方法,PCR-LDR方法,对78例急性髓系白血病患者（AML）和100例对照人群进行NQO1基因突变分析。结果：AML病例组NQO1基因T等位基因频率（43%）和TC/TT基因型频率（63%）均高于对照组（28%和43%）。携带TC/TT基因型的个体发生AML的相对风险度为其野生型（CC）的1.67倍（95%CI=1.212～2.727）。结论：NQO1基因多态性与AML遗传易感性相关,等位基因C对AML易感性有保护作用。     

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.     

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.     

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.     

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.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.