白细胞介素12对卡氏肺孢子虫感染的保护性免疫研究

目的：探讨白细胞介素１２（ＩＬ－１２）对卡氏肺孢子虫护一免疫作用。方法：用ＩＬ－１２作为佐剂和卡氏肺孢子虫主要表面糖蛋白（ＭＳＧ）一起免疫大鼠。结果：ＩＬ－１２＋ＭＳＧ可促进Ｔｈｌ细胞庆答，抑制Ｔh２细胞应答，增强脾细胞ＮＫ杀伤活性。结论：本研究提示，ＩＬ－１２可增强ＭＳＡＧ对卡氏肺孢子虫感染的保护性免疫作用。     

复方磺胺甲恶唑对肾移植后卡氏肺孢子虫肺炎的预防作用

背景：卡氏肺孢子虫肺炎是由卡氏肺孢子虫寄生于肺部引起的一种严重的致命性肺炎。复方磺胺甲恶唑是目前用于治疗卡氏肺孢子虫肺炎的一线药物,治疗量往往有明显的不良反应,小剂量预防用药临床疗效及毒副作用尚不清楚。目的：观察复方磺胺甲恶唑对肾移植后卡氏肺孢子虫肺炎的预防效果。方法：选择肾移植后1个月且无复方磺胺甲恶唑过敏者。肾移植后1个月至半年或1年常规服用复方磺胺甲恶唑（0.48g/d）。观察移植肝肾功能,感染情况,药物不良反应。结果与结论：2006年起,随访125例肾移植术后早期患者,73例术后1个月起常规服用复方磺胺甲恶唑（0.48g/d）至术后半年者,1例停药4个月后感染卡氏肺孢子虫肺炎死亡,47例服用复方磺胺甲恶唑（0.48g/d）至术后1年者,无感染卡氏肺孢子虫肺炎者,5例因复方磺胺甲恶唑过敏或医从性差未服用复方磺胺甲恶唑者,2例分别在术后4,5个月感染卡氏肺孢子虫肺炎,1例死亡。结果提示,肾移植术后1个月至1年常规服用复方磺胺甲恶唑（0.48g/d）,可有效预防卡氏肺孢子虫肺炎,临床无明显不良反应。     

卡氏肺孢子虫肺炎的护理进展

介绍了卡氏肺孢子虫肺炎（PCP）感染的临床特点,从提高病原体的检出率、低氧血症的观察与护理、高热护理、药物护理、保护性隔离、营养支持、心理护理、肺孢子虫病的预防策略方面综述了卡氏肺孢子虫肺炎的护理进展.     

AIDS合并卡氏肺孢子虫肺炎的护理

卡氏肺孢子虫肺炎（PCP）是艾滋病（AIDS）最常见的机会性感染之一。本文介绍了8例艾滋病合并卡氏肺孢子虫肺炎病人的护理，认为对此类病人的心理支持尤为重要，对其临床表现发热、咳嗽咳痰、呼吸困难、消瘦、霉菌感染等应及时给予对症处理，同时要加强自我防护，严防职业暴露。     

肾移植术后合并卡氏肺孢子虫肺炎患者的观察及护理

目的探讨肾移植术后合并发生卡氏肺孢子虫肺炎患者的治疗和护理对策。方法回顾性分析我院15例同种异体肾移植术后合并卡氏肺孢子虫肺炎患者的治疗效果和护理措施。结果 15例患者全部治愈。结论肾移植术后合并卡氏肺孢子虫肺炎死亡率较高,通过强化消毒隔离,加强基础护理和健康宣教等措施,可有效降低卡氏肺孢子虫肺炎的发生率,减轻感染后的症状,促进患者痊愈。     

卡氏肺孢子虫肺炎大鼠血清中IL-8的动态变化

目的 探讨卡氏肺孢子虫肺炎动物血清中IL-8的动态变化.方法 给SD大鼠皮下注射地塞米松建立肺孢子虫肺炎动物模型,改良的六亚甲基四胺银染色法检获肺组织中的肺孢子虫包囊,采用IL-8检测试剂盒检测大鼠血清中IL-8的含量.结果 对照组、第7、8、9周感染组的IL-8含量分别为(16.554±1.211)、(17.267±...     

肾移植后合并卡氏肺孢子虫肺炎：10年同一机构378例中的12例

背景：在肾移植后早期,由于免疫抑制剂用量较大,患者的免疫功能明显受到抑制,卡氏肺孢子虫肺炎在此期间相对高发。目的：分析肾移植后并发卡氏肺孢子虫肺炎的临床特点、诊治及预防。方法：收集佛山市第一人民医院肾内科2000-11/2010-07肾移植378例中并发卡氏肺孢子虫肺炎12例患者的临床资料,分别对其发病时间、易感因素、诊断方法、临床表现及治疗方案、预防效果进行回顾性分析。结果与结论：发病时间为移植后5.3（3~11）个月。12例患者均有发热,体温达38.0～40.2℃,气促及紫绀。9例轻微咳嗽,5例少量白痰,1例红色泡沫痰。5例合并细菌感染,2例合并真菌感染,2例合并巨细胞病毒感染,1例合并结核。服用他克莫司患者感染发生率为7.8%（7/89）,服用环孢素A患者感染发生率为1.7%（5/289）。9例使用呼吸机,2例使用呼吸机无创性连续鼻或口鼻面罩治疗。8例痊愈,2例治疗中出现血小板减少致脑出血死亡,1例合并真菌感染死亡,1例合并血气胸死亡。治疗期间,无排斥反应发生。说明早期诊断,联合用药,减少免疫抑制剂用量是提高卡氏肺孢子虫肺感染治愈率的关键。     

复方磺胺甲恶唑对肾移植后卡氏肺孢子虫肺炎的预防作用

背景:卡氏肺孢子虫肺炎是由卡氏肺孢子虫寄生于肺部引起的一种严重的致命性肺炎.复方磺胺甲恶唑是目前用于治疗卡氏肺孢子虫肺炎的一线药物,治疗量往往有明显的不良反应,小剂量预防用药临床疗效及毒副作用尚不清楚.目的:观察复方磺胺甲恶唑对肾移植后卡氏肺孢子虫肺炎的预防效果.方法:选择肾移植后1个月且无复方磺胺甲恶唑过敏者.肾移植后1个月至半年或1年常规服用复方磺胺甲恶唑(0.48 g/d).观察移植肝肾功能,感染情况,药物不良反应.结果与结论:2006年起,随访125例肾移植术后早期患者,73例术后1个月起常规服用复方磺胺甲恶唑(0.48 g/d)至术后半年者,1例停药4个月后感染卡氏肺孢子虫肺炎死亡,47例服用复方磺胺甲恶唑(0.48 g/d)至术后1年者,无感染卡氏肺孢子虫肺炎者,5例因复方磺胺甲恶唑过敏或医从性差未服用复方磺胺甲恶唑者,2例分别在术后4,5个月感染卡氏肺孢子虫肺炎,1例死亡.结果提示,肾移植术后1个月至1年常规服用复方磺胺甲恶唑(0.48 g/d),可有效预防卡氏肺孢子虫肺炎,临床无明显不良反应.     

肝脏组织S-腺苷甲硫氨酸酶与卡氏肺孢子虫肺炎的相关性研究

目的探讨卡氏肺孢子虫肺炎大鼠模型肝脏组织S-腺苷甲硫氨酸酶的变化。方法给SD大鼠皮下注射地塞米松建立肺孢子虫肺炎动物模型,采用改良的六亚甲基四胺银染色法检测获得肺组织中的肺孢子虫包囊,利用组织S-腺苷甲硫氨酸酶检测试剂盒测定肝脏组织中S-腺苷甲硫氨酸酶的含量。结果感染组大鼠全部感染了卡氏肺孢子虫,感染率为100%;肝脏组织中S-腺苷甲硫氨酸酶的含量为(0.254 5±0.067 9)μmol/mg,正常对照组大鼠卡氏肺孢子虫包囊的检出率为0%,肝脏组织中S-腺苷甲硫氨酸酶的含量为(0.401 4±0.087 8)μmol/mg,感染组与正常对照组比较,差异有统计学意义(P<0.05)。结论卡氏肺孢子虫肺炎大鼠肝脏组织中S-腺苷甲硫氨酸酶的含量明显降低,提示测定肝脏组织S-腺苷甲硫氨酸酶的含量可以辅助诊断卡氏肺孢子虫肺炎。     

1例冰毒中毒合并卡氏肺孢子虫肺炎的急救与护理

卡氏肺孢子虫肺炎（pneumocystis carinii pneumonia,PCP）是一种机会感染性疾病[1]。是由卡氏肺孢子虫引起的肺部非化脓间质性炎症,多发生在早产儿、营养不良的婴儿和有免疫抑制的儿童或成人。近年来由于肾上腺皮质激素、器官移植后免疫抑制剂的应用、肿瘤放化疗及毒品的滥用,发病率明显上升,已成为这类病人最常见的机会感染与致死的主要病因。我院2013年1月收治1例冰毒中毒合并卡氏肺孢子虫肺炎病人,经临床治疗治愈出院。现报告如下。     

Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat.

Pneumocystis carinii is a major opportunistic pathogen and a leading cause of morbidity in patients with AIDS. CD4+ cells have been shown to be important in host defenses against P. carinii, but the antigen(s) involved with this response have not been identified. We undertook the present study to determine whether the major surface glycoprotein (MSG) of P. carinii contains epitopes that can elicit a protective cellular immune response. Spleen cells and purified CD4+ cells isolated from Lewis rats, pulsed 1-4 d with MSG, and injected into corticosteroid-treated Lewis rats with pneumocystosis resulted in significant reduction in the P. carinii burden, as judged by organism quantitation and lung histology. The protective response demonstrated by the donor cells was dependent on previous exposure to P. carinii, cell concentration, and time of incubation with MSG. In addition, reconstitution with MSG-specific CD4+ cells resulted in an early hyperinflammatory response within the lungs of these animals with a high percentage of mortality. Thus, in this model, MSG can elicit an immune response mediated by CD4+ cells, which has a harmful as well as helpful effect on the host, and these responses occur despite the presence of corticosteroids.     

Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

BACKGROUND: The major surface glycoprotein (MSG) is an abundant, immunogenic glycoprotein located on the surface of Pneumocystis carinii. Little is known about the proinflammatory effects of MSG. DESIGN: We have investigated the effect of human MSG on the secretion of the chemokines interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P < 0.01). Time course experiments showed increases in IL-8 release at 4 h, 8 h and 24 h compared with control cultures (all P < 0.01). There was a minor (13%) dose- and time-related increase in MCP-1 release at 24 h (P = 0.02). Co-incubation of MSG with mannan or beta-glucan decreased IL-8 release by 48% and 42% respectively, suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P < 0.01). Ribonuclease protection assays for steady-state IL-8 mRNA showed that increases in response to MSG stimulation occurred by 4 h and persisted throughout 8 h of stimulation. CONCLUSION: These findings suggest that MSG can alter alveolar epithelial cytokine release and may be capable of modulating the local inflammatory response in this manner.     

Interaction of Pneumocystis carinii with dendritic cells and resulting host responses to P. carinii

To assess the interaction of Pneumocystis carinii with dendritic cells (DCs), and the consequences of the response of the host immune system to P. carinii antigens when DC are pulsed with P. carinii, murine DC were pulsed with P. carinii, and the resultant P. carinii host responses assessed in vitro and in vivo. P. carinii interacted with murine bone marrow-derived DC in vitro in part via mannose receptors. DC pulsed with P. carinii did not demonstrate increased expression of the cell surface markers MHC II, CD40, CD54, CD80 (B7.1), and CD86 (B7.2). The release of interleukin (IL)-4 was increased, but there was no increase in the release of interleukin (IL)-12p40, IL-10, tumor necrosis factor-alpha, IL-6, and nitrite compared with naive DC. In vivo administration of DC pulsed with P. carinii induced a P. carinii-specific response, generating CD4+ cells that proliferated and released IL-4, but not interferon-gamma, in response to P. carinii-pulsed DC in vitro. In vivo administration of DC pulsed with P. carinii also induced P. carinii-specific immunoglobulin (Ig)G1, IgG2a, and IgG2b, but not IgG3, antibodies in serum, and lung lavage fluid. Finally, CD4+ depleted mice immunized with DC pulsed with P. carinii demonstrated suppression of lung growth of P. carinii after intratracheal challenge with P. carinii at 3 and 16 weeks after immunization. These observations provide insight into DC-P. carinii interactions, and support the concept that a vaccine that includes DC pulsed with P. carinii can mount a humoral and T helper 2-type cellular response to P. carinii sufficient to suppress the growth of P. carinii in the lung.     

Expression of variants of the major surface glycoprotein of Pneumocystis carinii

Previously, we have shown that a multicopy family of related but unique genes encodes the major surface glycoprotein (MSG) of Pneumocystis carinii. To examine whether different members of this gene family are expressed by P. carinii, antisera were prepared against peptides whose sequences were determined from the deduced amino acid sequences of variants of rat-derived MSG. Immunohistochemical staining of serial sections of rat lungs of infected animals showed that at least three variants of MSG were expressed in an individual lobe, that there was a focal expression of these variants within the lung, and that the relative numbers of these foci were different. Indirect immunofluorescent staining of purified P. carinii organisms using these antisera revealed that at least three variants of MSG were present in organisms isolated from an individual rat and that both cysts and trophozoites reacted with each antiserum. A substantial difference in the fraction of organisms reacting with a specific antipeptide antiserum was seen when comparing organisms isolated from rats raised in a single colony over a period of two years as well as organisms isolated at one time point from rats raised in different colonies. This demonstration of antigenic variation in P. carinii supports the hypothesis that P. carinii utilizes such variation for evading host defense mechanisms.     

Effect of T-cell transfer on Pneumocystis carinii infection in nude mice

The effect of transfer of spleen lymphocytes from euthymic heterozygote littermates (nu/+) or rabbit antiserum on Pneumocystis carinii (P. carinii) infection in nude (nu/nu) mice was investigated. After intravenous administration of nu/+ spleen T-cells, the number of cysts in the lung of previously infected mice was markedly decreased at day 14 and further at day 30. Intense cellular reactions were seen at day 14 and subsided lesions at day 30. Increased IgG antibody titers were observed at days 14 and 30. Multiple treatments with immune rabbit serum after infection were not effective for reducing the cyst number in the lung, neither enhanced cellular reaction, while the immune serum administered prior to infection prolonged the survival time. The results indicated an important role of T-cell mediated immunity for the resistance to P. carinii infection in mice.     

Pneumocystis carinii pneumonia therapy with 9-deazainosine in rats

An inosine analog, 9-deazainosine, has previously been demonstrated to inhibit Pneumocystis carinii in culture with WI-38 cells. The present study shows that it is also effective against Pneumocystis carinii in immunosuppressed Sprague-Dawley rats with Pneumocystis carinii pneumonia. After 8 wk of immunosuppression, rats that developed severe Pneumocystis carinii pneumonia were treated with either 9-deazainosine or served as controls. After 15 days of therapy, animals were sacrificed and severity of infection determined by morphologic examination of lungs for numbers of Pneumocystis carinii. Treated animals had greatly reduced numbers of Pneumocystis carinii trophozoites and cysts, compared with controls. This drug shows promise for therapy of Pneumocystis carinii pneumonia and should be studied further.     

Effects of atovaquone and diospyrin-based drugs on ubiquinone biosynthesis in Pneumocystis carinii organisms

The naphthoquinone atovaquone is effective against Plasmodium and Pneumocystis carinii carinii. In Plasmodium, the primary mechanism of drug action is an irreversible binding to the mitochondrial cytochrome bc(1) complex as an analog of ubiquinone. Blockage of the electron transport chain ultimately inhibits de novo pyrimidine biosynthesis since dihydroorotate dehydrogenase, a key enzyme in pyrimidine biosynthesis, is unable to transfer electrons to ubiquinone. In the present study, the effect of atovaquone was examined on Pneumocystis carinii carinii coenzyme Q biosynthesis (rather than electron transport and respiration) by measuring its effect on the incorporation of radiolabeled p-hydroxybenzoate into ubiquinone in vitro. A triphasic dose-response was observed, with inhibition at 10 nM and then stimulation up to 0.2 microM, followed by inhibition at 1 microM. Since other naphthoquinone drugs may also act as analogs of ubiquinone, diospyrin and two of its derivatives were also tested for their effects on ubiquinone biosynthesis in P. carinii carinii. In contrast to atovaquone, these drugs did not inhibit the incorporation of p-hydroxybenzoate into P. carinii carinii ubiquinone.     

A reliable silver staining method for identification of Pneumocystis carinii in histologic sections

The acquired immune deficiency syndrome (AIDS) is characterized by the development of Kaposi's sarcoma and several opportunistic infections including pneumonia caused by Pneumocystis carinii. As a staining method for Pneumocystis carinii, the methenamine-silver nitrate method has been used routinely. Most of fungi can be stained easily by this technique but the identification of Pneumocystis carinii is not always easy. The author has improved the method by using ammoniacal silver nitrate and found that this was a reliable staining method for Pneumocystis carinii. Moreover, this method proved to be superior to others in demonstrating Pneumocystis carinii in histologic sections.     

Electrocardiogram in Pneumocystis carinii pneumonia: can it be used as a prognostic variable?

OBJECTIVE: Many prognostic variables have been studied in patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome (AIDS). The role of the electrocardiogram in this setting has not been previously evaluated. We analyzed the admission electrocardiogram in patients with Pneumocystis carinii pneumonia and AIDS in an attempt to identify electrocardiogram findings that could be associated with adverse clinical outcomes and worse prognostic variables. DESIGN: A retrospective medical chart review. SETTING: All confirmed cases of Pneumocystis carinii pneumonia in patients positive for human immunodeficiency virus admitted to Albert Einstein Medical Center from 1994 to 2000. METHODS: Patients were assigned increasing severity ranks based on the findings on the admission electrocardiogram (normal sinus rhythm, sinus tachycardia, and right ventricular strain pattern). Data were extracted regarding study outcomes (admission to intensive care unit, mechanical ventilation, and hospital mortality) and prognostic variables. MAIN RESULTS: Of the 40 study patients, 14 (35%) had normal sinus rhythm, 15 (37.5%) had sinus tachycardia, and 11 (27.5%) presented with signs of right ventricular strain. The number of admissions to the intensive care unit, use of mechanical ventilation, and hospital mortality rate all increased with the severity of the electrocardiogram findings (p < or =.03). The serum lactate dehydrogenase concentrations and the alveolar-arterial oxygen gradient both increased with the severity of the electrocardiogram findings (p < or =.02). CONCLUSION: Electrocardiogram findings of sinus tachycardia and right heart strain are common in Pneumocystis carinii pneumonia. These findings are associated with adverse clinical outcomes as well as worsening of prognostic variables. The electrocardiogram may be useful in predicting outcome in patients with Pneumocystis carinii pneumonia.     

Inhibitors of sterol biosynthesis and amphotericin B reduce the viability of pneumocystis carinii f. sp. carinii

Pneumocystis carinii synthesizes sterols with a double bond at C-7 of the sterol nucleus and an alkyl group with one or two carbons at C-24 of the side chain. Also, some human-derived Pneumocystis carinii f. sp. hominis strains contain lanosterol derivatives with an alkyl group at C-24. These unique sterols have not been found in other pathogens of mammalian lungs. Thus, P. carinii may have important differences in its susceptibility to drugs known to block reactions in ergosterol biosynthesis in other fungi. In the present study, inhibitors of 3-hydroxy-3-methyglutaryl coenzyme A reductase, squalene synthase, squalene epoxidase, squalene epoxide-lanosterol cyclase, lanosterol demethylase, Delta(8) to Delta(7) isomerase, and S-adenosylmethionine:sterol methyltransferase were tested for their effects on P. carinii viability as determined by quantitation of cellular ATP levels in a population of organisms. Compounds within each category varied in inhibitory effect; the most effective included drugs targeted at squalene synthase, squalene epoxide-lanosterol cyclase, and Delta(8) to Delta(7) isomerase. Some drugs that are potent against ergosterol-synthesizing fungi had little effect against P. carinii, suggesting that substrates and/or enzymes in P. carinii sterol biosynthetic reactions are distinct. Amphotericin B is ineffective in clearing P. carinii infections at clinical doses; however, this drug apparently binds to sterols and causes permeability changes in P. carinii membranes, since it reduced cellular ATP levels in a dose-dependent fashion.