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。     

上海地区805例成人急性白血病世界卫生组织亚型的临床分析

目的 分析上海地区24家医院急性白血病(AL)世界卫生组织(WHO)亚型的分布,并与国外资料进行比较,探讨我国AL患者WHO亚型的分布特点.方法 收集连续样本,对中美联合上海市白血病协作组805例AL患者同时采用FAB和WHO分型标准进行分型诊断.结果 本组AL中急性髓系白血病(AML)77.4%(623/805),急性淋巴细胞白血病(ALL)20.4%(164/805),AML和ALL之比为3.8:1.伴有重现性细胞遗传学异常AML占36.4%,AML伴多系病态造血占17.7%,不属于上述分类的AML占45.9%.FAB分型中M4最多,占33.9%,M3和M4比例高于国外,M1比例低于国外报道.与上海市1984-1994年AL资料相比,M4亚型比例增多,M1和M5亚型比例减少.AML染色体异常率61.7%,AML伴t(15;17)比例高于国外,染色体预后良好组占30.1%,预后中等组占51.6%,预后不良组占18.3%,预后良好组比例高于国外.ALL中前体B细胞ALL占绝大多数(82.3%),ALL中t(9;22)占28.2%.结论 AML伴t(15;17)和M4比例高于国外,染色体预后良好组比例高于国外,AML的WHO分型和染色体异常类型与国外有所不同.与上海市1984-1994年AL资料相比,AML的亚型分布有所变化.     

形态学、免疫学、细胞遗传学联合检测诊断急性白血病的临床意义

为探讨形态学、免疫学、细胞遗传学联合检测对急性白血病(AL)诊断、治疗、预后判断等方面的临床意义，对初诊为AL的39例患者分别进行了骨髓细胞形态学、免疫学及染色体检测。并按照FAB标准进行形态学(组织化学染色)分型；采用间接免疫荧光法标记活细胞膜表面分化抗原(CD)进行免疫学分型；采用24小时培养法制备染色体标本，G带显示法进行染色体检查。结果：39例患者经形态学检查确诊为AL，其中急性淋巴细胞白血病(ALL)8例，急性非淋巴细胞白血病(ANLL)29例，2例难以分型；免疫学诊断为ALL8例(其中2例伴髓系抗原表达)，ANLL29例(其中4例伴淋巴细胞抗原表达)，2例形态学难以分型者，诊断为急性杂合性白血病。免疫学与形态学分型符合率94．9％(37／39)。39例中染色体核型异常18例。本研究结果还显示，经临床治疗后染色体复杂畸形者缓解率低，正常核型及某些染色体核型[如t(15；17)]者缓解率较高。认为形态学、免疫学、细胞遗传学联合检测可提高AL诊断的准确性，有助于制定治疗方案及判断预后。     

成人急性髓系白血病189例伴有t(8;21)的遗传学特点及预后分析

目的探讨伴有t（8;21）的成人急性髓系白血病（AML）的细胞遗传学特点及预后意义。方法分析我院检测的189例成人t（8;21）的细胞遗传学和临床预后特点。结果单纯t（8;21）（q22;q22）63例,占33．3％;伴有附加异常的126例,占66．7％;单纯性染色体丢失77例占总数的40．7％,其中-Y占男性患者的46．7％（63／135）,-X占女性患者的25．9％（14／54）。有附加异常的126例中,单纯性染色体丢失77例（61．1％）;9q-16例（12．7％）;＋4者5例（4．0％）;7q-6例（4．8％）;四倍体（4N）2例（1．6％）;变异易位7例（5．6％）。此组患者的缓解率较高（87．0％）,生存期较长（中位生存期21．6个月）。附加异常中＋4和4N组预后较差。荧光原位杂交技术是诊断t（8;21）AML较为准确和可靠的方法,特别是对于变异易位、复杂易位和隐匿变异易位的病例。结论t（8;21）常合并附加异常,附加异常的种类会影响t（8;21）AML患者的预后。     

急性白血病P—gp和GSTπ的表达及临床意义

目的：探讨初诊急性白血病（AL）耐药机制。方法：应用免疫酶法（APAAP）检测74例初诊急性白血病（AL）P－gp、GSTπ的表达及临床意义。结果：急性髓性白血病（AML）患者P－gp阳性率21％,GSTπ阳性率27％,两者均阳性13％;急性淋巴白血病（ALL）患者P－gp阳性率14％,GSTπ阳性率50％,两者均阳性9％。无论是AML还是ALL两者均无相关性。P-gp和GSTπ均阳性者完全缓解（CR）明确低于均阴性者（P＜0．05）。结论：P－gP、GSTπ共阳性是AL预后不良的重要指标之一。     

11q23异常成人急性白血病临床及实验室特征分析

目的 研究11q23异常成人急性白血病(AL)的实验室资料与其临床特征和预后的关系.方法 对1992年8月至2003年11月中国协和医科大学血液学研究所收治的23例11q23异常的成人AL的临床和实验室资料进行回顾性分析.结果 23例11q23异常的患者中14例为急性髓性白血病(AML),7例为急性淋巴细胞白血病(ALL),1例为急性杂合细胞白血病(HAL),1例为急性未分化白血病(AUL).AML中以AML-M4及AML-M5为主,ALL中以前B-ALL为主.异常核型主要为11q23缺失(n=9)和t(4;11)(n=8).23例AL的中位存活时间为175 d,14例AML的中位存活时间为185 d,7例ALL的中位存活时间为167 d.结论 11q23异常AL在成人主要见于AML-M4及AML-M5和前B-ALL,具有高白细胞、易于髓外浸润、化疗缓解率低、预后差等临床特点,为预后不良的细胞遗传学改变.     

41例急性髓细胞白血病患者的细胞遗传学分析

目的了解急性髓细胞白血病的细胞遗传学特征及其与预后的关系。方法对41例以FAB分类标准确诊的AML初发患者的细胞遗传学资料进行回顾性分析,应用骨髓细胞短期培养法制备染色体标本,以R显带技术进行核型分析。结果共检出异常核型16例（39．0％）,单纯数目异常的有2例,染色体结构异常的12例,其余2例同时有数目及染色体结构异常。本组中最常见的结构异常为t（15;17）,t（8;21）。结论细胞遗传学对急性髓细胞白血病的诊断具有重要的意义,特别是与FAB分型具有特异性的t（15;17）,t（8;21）染色体异常对急性白血病的诊断具有决定意义。     

急性早幼粒细胞白血病形态学和细胞遗传学的临床研究

目的 探讨形态学和细胞遗传学(MIC)联合检测对急性早幼粒细胞白血病(M3)的临床意义。方法 将MIC技术用于32例M3患者的诊断、分型及预后评价。结果 形态学检查26例M3a，中2例和6例M3b中3例曾误诊为其它白血病，经核型分析确诊。骨髓染色体分析正常3例(2／32)，28例(28／32)有t(15：17)，1例(1／32)具有变易移位，可评价的20例中19例(19／21)达到CR，具有复杂核型和变易移位各1例未能取得缓解。结论 MIC联合检测对M3的诊断、分型、评价预后等有重要价值。     

肺耐药蛋白在急性白血病中的表达及意义

目的 探讨急性白血病（AL）患者骨髓单个核细胞肺耐药蛋白（LRP）的表达及意义。方法 采用LRP单克隆抗体、流式细胞技术分别测定15例单纯缺铁性贫血患者（对照组）和65例AL患者（AL组）LRP的表达率。结果 LRP的表达率在初治和复发／难治急性淋巴细胞白血病（ALL）患者分别高于初治和复发／难治急性髓细胞白血病（AML）患者（P均〈0．05）;AML中M5亚型表达率高于M3亚型（P〈0．05）。初治及复发／难治LRP（＋）者缓解率明显低于LRP（-）者（P〈0．05）。结论 LRP的表达与AL患者临床预后密切相关,化疗前检测LRP表达率有助于个体化治疗和预测疗效。     

免疫分型结合基因重排对成人急性淋巴细胞白血病诊断及预后的判断价值

目的：探讨用免疫分型组合免疫球蛋白重链（IgH)及T细胞受体γ（TCRγ）基因重排对急性淋巴细胞白血病（ALL）的分型诊断及预后的判断价值。方法：免疫分型采用碱性磷酸酶抗性磷酸酶复合物（APAAP）免疫组化法,基因重排采用多聚酶链反应技术（PCR法）检测58例初治成人ALL患者。结果：①通过免疫分型检测,58例ALL中,43例（74．1％）为不带髓系相关标记的ALL（My^-ALL),15例（25．9％）为带髓系相关标记的ALL（My^ ALL),以CD15最常见。②采用PCR法检测IgH基因重排和TCRγ基因重排发现,58例ALL中有79．3％（46／58）免疫分型与基因重排结果完全吻合,即T－ALL出现TCRγ基因重排阳性,B－ALL出现IgH基因重排阳性,20．7％（12／58）基因重排结果与免疫分型不能完全吻合。③58例ALL经DOLP或DOCP方案1个疗程后,My^-ALL CR为72．1％（31／43）,My^ ALL为66．7％（10．15）;ALL不同阶段CR率分别是：T－ALL为82．4％（14／17）,ProB-ALL为50．0％（3／6）,C－ALL为90．5％（19／21）,RreB-ALL为33．3％（4／12）,成熟B－ALL为50．0％（1／2）;经基因重排检测与免疫分型吻合的ALL CR率为71．7％（33／46）,不吻合的ALL66．7％（8／12）。结论：对于白血病的分型应在FAB分型的基础上加用免疫分,可提高确诊率且对预后判断有价值;基因重排诊断仅有参考价值,对预后尚无指导意义。     

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.     

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.     

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.