肿瘤抗原冲击致敏的树突状细胞在骨髓移植小鼠中抗白血病的免疫反应

目的研究肿瘤抗原冲击致敏(pulsedwithwholetumorlysates,TP)的树突状细胞(dendriticcells,DC)在骨髓移植(bonemarrowtransplantation,BMT)小鼠中诱导特异性的抗白血病免疫反应。方法2002-06~2003-06在山东大学齐鲁医院使用mGM-CSF+mIL-4培养诱导骨髓细胞分化,将L7212白血病细胞的冻融抗原冲击致敏DC,培养制备肿瘤抗原冲击致敏的树突状细胞(tumorlysatespulseddendriticcells,TP-DC),将TP-DC重复免疫BMT后615小鼠,同时设立对照组,观察各组小鼠的生存期及存活率。结果TP-DC能诱导产生针对L7212白血病细胞的特异性细胞毒性,与对照组相比差异显著(F=391·77,P<0·01)。TP-DC重复免疫组小鼠的生存期及存活率明显高于对照组,差异显著(χ2=18·14,P<0·01)。结论TP-DC重复免疫在BMT小鼠中产生明显的抗白血病免疫反应。     

白血病抗原冲击致敏的树突状细胞诱导的抗肿瘤免疫反应

目的：研究树突状细胞(DC)的体外培养扩增及诱导特异性的抗肿瘤免疫反应。方法：使用mGM-CSF加mIL-4培养诱导骨髓细胞分化，采用反复冻融法制备L7212白血病细胞的冻融抗原(TAA)，在DC培养的第3天加入TAA，将TAA冲击致敏的DC与T淋巴细胞共培养，获得肿瘤特异性细胞毒性T淋巴细胞(CTL)，采用MTT法检测CTL对L7212细胞的杀伤作用及其对野生型L7212细胞再攻击的免疫保护作用。结果：MTT检测发现CTL对L7212细胞有特异性杀伤抑制作用，L7212抗原冲击致敏的DC能显著提高和延长野生型L7212细胞再攻击小鼠的生存率和存活期。结论：mGM-CSF和mIL-4配伍可有效地从小鼠骨髓细胞中诱导出大量的成熟的功能性DC，L7212白血病TAA冲击致敏的DC可诱导机体产生较强的抗肿瘤免疫反应。     

DCCIK细胞抗肿瘤的基础研究及临床应用进展

树突状细胞（dendritic cells，DC）分布于除脑和睾丸以外的身体的任何组织，是目前所知的功能最强大的专职抗原递呈细胞（antigen presenting cells，APC），亦是体内唯一具有激活幼稚T淋巴细胞诱导初次免疫应答能力的APC。     

肝癌抗原肽冲击转染p53的树突状细胞对荷瘤小鼠免疫功能的影响

树突状细胞（DC）是体内功能最强大的专职性抗原呈递细胞，它们能高效摄取、处理抗原，并将多肽呈递给静息型T细胞，引起针对此抗原的特异性免疫反应。我们将全长野生型p53基因（wt—p53）转染小鼠骨髓来源的DC，然后用肝癌抗原肽修饰已转染野生型p53的DC（wt—p53DC），利用这种DC诱导小鼠脾脏淋巴细胞特异的细胞毒性T淋巴细胞（CTL）。     

树突状细胞调节和细胞因子诱导的杀伤细胞的抗肿瘤机制及其在结直肠癌治疗中的应用前景

利用细胞因子诱导树突状细胞（dendritic cell，DC）和细胞因子诱导的杀伤细胞（cytokine induced killer，CIK细胞），以肿瘤抗原冲击DC，将经过抗原冲击的DC和CIK细胞按一定比例混合进行共培养，得到一种新的免疫效应细胞群，即DC调节和细胞因子诱导的杀伤细胞（DCIK细胞）。DCIK细胞具有识别和特异性杀伤恶性细胞的作用，打破了放化疗“敌我不分”的状况。DCIK细胞不但存活率高，增殖能力强．而且对肿瘤细胞具有特异性杀伤能力，为肿瘤免疫治疗开创了一条新的途径。     

乙型肝炎患者外周血树突状细胞的培养及表型分析

树突状细胞（dendritic cells，DC）是已知体内功能最强及唯一能活化静息T细胞的专职抗原递呈细胞,并且在增强或调节细胞介导的免疫反应中起管决定性作用．在CHB患者中不仅DC的表型不成熟并且存在着功能的缺失，树突状细胞这种功能改变及数量变化与乙型肝炎患者针对HBV特异的CTL反应下降有密切关系。     

树突状细胞与肝脏疾病

免疫反应的产生首先是由抗原提呈细胞(antigenpresenting cells,APC)捕获抗原,经其加工处理后将抗原信息传递给T,B淋巴细胞,从而引发一系列的特异性免疫应答.APC包括树突状细胞(dendritic cells,DC)、巨噬细胞(MΦ)、B细胞等,其中DC是人体内最具潜能的抗原提呈细胞(APC),能在体内外直接激活纯真(naive)T细胞,提呈抗原给MHC-Ⅰ类限制性CD8+和MHC-Ⅱ类限制性CD4+T淋巴细胞,诱导特异性免疫应答[1-6].     

慢性乙型肝炎患者树突状细胞特点及其免疫治疗

树突状细胞（DC）是诱导和维持抗原特异性免疫应答非常重要的抗原提呈细胞（APC），研究表明慢性乙型肝炎（CHB）患者体内DC功能下降，这可能是导致CHB的重要原因之一。DC增强免疫疗法的基本原理是提高CHB患者体内DC功能，诱导强烈的HBV特异性免疫反应清除病毒。     

化疗药物诱导的肺癌死亡细胞致敏树突状细胞的抗肿瘤免疫研究

目的探讨化疗药物诱导的肺癌死亡细胞致敏树突状细胞（DC）的免疫应答及对肺癌细胞的免疫杀伤效果。方法用粒-巨噬细胞集落刺激因子（GM—CSF）和白介素4（IL-4）从胎儿脐血中分化、诱导DC。用足叶乙甙与顺铂在体外诱导培养的人肺癌系A549细胞死亡。DC与死亡的肿瘤细胞培育后，对DC表型变化及抗肿瘤效果进行检测。结果负载死亡的A549细胞之后并不能促使未成熟DC（iDC）分化为成熟DC（mDC），而在TNF—α的作用下能够成为mDC。死亡的A549细胞负载后的mDC由其所激发和扩增的T细胞细胞数以及对肺癌细胞的杀伤效果显著。结论化疗药物诱导的肺癌死亡细胞在体外能有效地致敏DC产生抗肿瘤免疫反应。     

DC—CIK坌田胞治疗研究

细胞因子诱导的杀伤细胞（cytokine—inducedkillor，CIK）是一类新型抗肿瘤效应细胞，能在体外被诱导并大量增殖，与以往报告的一些抗肿瘤效应细胞相比，CIK细胞杀瘤活性更强、杀瘤谱更广。树突状细胞（dendritic cell，DC）是最有效的专职抗原提呈细胞，成熟的DC细胞可通过Ⅱ型组织相容性抗原（MHC-Ⅱ）等途径提呈肿瘤抗原，     

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.