Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies

Mucositis occurs in ≤ 98% of patients undergoing stem cell transplant for haematological malignancies and is associated with significant morbidity and mortality. Patients with severe mucositis have more pain, more difficulty with daily activities such as talking and eating, and are more likely to have bacteraemia. Palifermin is a keratinocyte growth factor that has been shown to decrease severity and duration of mucositis with a concurrent decrease in patient-reported symptoms and use of narcotics and total parenteral nutrition. Research is ongoing into palifermin’s potential ability to decrease graft-versus-host disease and improve reconstitution of functional T lymphocytes after allogeneic stem cell transplant, to hasten wound healing and to reduce mucositis following external beam radiation therapy in solid tumour patients.     

Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies

Mucositis occurs in < or = 98% of patients undergoing stem cell transplant for haematological malignancies and is associated with significant morbidity and mortality. Patients with severe mucositis have more pain, more difficulty with daily activities such as talking and eating, and are more likely to have bacteraemia. Palifermin is a keratinocyte growth factor that has been shown to decrease severity and duration of mucositis with a concurrent decrease in patient-reported symptoms and use of narcotics and total parenteral nutrition. Research is ongoing into palifermin's potential ability to decrease graft-versus-host disease and improve reconstitution of functional T lymphocytes after allogeneic stem cell transplant, to hasten wound healing and to reduce mucositis following external beam radiation therapy in solid tumour patients.     

重组人角质细胞生长因子对放射性和放疗性口腔黏膜炎的防治作用

目的评价重组人角质细胞生长因子(rhKGF)对口腔黏膜炎(OM)的预防和治疗作用。方法以MTT法检测rhKGF对32D-KGFR细胞体外增殖的促进作用。大鼠头部经15.3 Gy 60Co辐射制备放射性OM模型,预防组在照射前3 d iv给予rhKGF 0.75,1.5和3 mg.kg-1或帕利非明1.5 mg.kg-1,每天1次,共3次;预防+治疗组在照射前3 d及照射后第2天和第4天iv给予rhKGF 1.5 mg.kg-1,共5次。小鼠iv给予5-氟尿嘧啶50 mg.kg-1,每天1次,连续4 d,制备化疗性OM模型,预防组在化疗开始前3 d iv给予rhKGF1.25,2.5,5 mg.kg-1或帕利非明2.5 mg.kg-1,每天1次,共3次;预防+治疗组在化疗开始前3 d及末次化疗后第2天和第4天iv给予rhKGF 2.5 mg.kg-1,共5次。通过观察临床症状、进食量、体质量变化、死亡率和OM发生率以及组织形态变化评价对OM的预防和治疗作用。结果 rhKGF 6.25～100μg.L-1可促进32D-KGFR细胞增殖反应。在放射性OM模型中,正常对照组、模型组、rhKGF 0.75,1.5和3 mg.kg-1预防组、预防+治疗组及帕利非明预防组大鼠OM发生率分别为0/12,12/12,8/12,6/12,5/12,5/12和5/12,rhKGF 1.5和3.0 mg.kg-1预防组、预防+治疗组和帕利非明预防组在放疗后第6天大鼠进食量显著高于模型组(P<0.05),第6和12天时各给药组体质量均显著高于模型组(P<0.05);另外,各给药组OM症状积分均降低,出现时间延迟,病程缩短。在化疗模型中,正常对照组、模型组、rhKGF预防1.25,2.5,5 mg.kg-1组、预防+治疗组及帕利非明预防组小鼠OM发生率分别为0/16,16/16,10/16,8/16,5/16,10/16和6/16,各给药组在末次化疗后第3和6天能显著缓解化疗引起的进食量减少;与模型组比较,rhKGF和帕利非明预防组小鼠肠黏膜厚度增加,绒毛膜上皮细胞增加,杯状细胞饱满粗大,小肠隐窝深度可见,绒毛形态正常,尤以rhKGF 2.5 mg.kg-1预防组作用最明显;rhKGF预防+治疗组的作用不及同剂量rhKGF预防组。结论rhKGF可预防放射性或化疗所致OM。     

Recombinant human keratinocyte growth factor attenuates apoptosis in elastase induced emphysematous mice lungs

Alveolar cell apoptosis is one of the potential factors involved in the pathogenesis of emphysema. Recently, exogenous recombinant human keratinocyte growth factor (rHuKGF) has been reported to induce the regeneration of gas exchange structures. Therefore, the rationale of the present study was to investigate the potential effect of rHuKGF in ameliorating tissue destruction in the emphysematous mice lungs. Four experimental groups (i.e. control-, emphysema-, therapy- and therapy control-group) were prepared. Subsequently, lungs from each mouse were collected for comet assay, elastase activity assay, antioxidant activity assay and real-time PCR based analyses. Comet assay analysis demonstrated the reduced tail DNA % and olive tail moment in therapy group. rHuKGF supplementation in emphysematous mice caused a significant reduction in the elastase activity levels along with reduction in activity of CAT, SOD and GPx. Furthermore, based on mRNA expression studies, the supplementation of rHuKGF ameliorated the induced apoptosis pathway in emphysematous mice lungs. Moreover, due to rHuKGF supplementation, TNF-α and p53 expression and production were markedly decreased in emphysematous mice lungs. Thus, therapeutic supplementation of rHuKGF might have reversed the alveolar cell loss in elastase induced emphysematous mice lungs by reducing DNA damage and maintaining antioxidant activities.     

Regulation of epidermal growth factor binding in a human keratinocyte cell line by 2,3,7,8-tetrachlorodibenzo-p-dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) decreased the binding of epidermal growth factor (EGF) by the human keratinocyte cell line SCC-12F. This response was concentration dependent (half-maximal effective concentration, EC50 = 1.8 nM) and stereospecific. Scatchard analysis of EGF binding indicated that treatment with TCDD resulted in a loss of high-affinity (Kd = 0.28 nM) binding sites. This loss was accompanied by a concomitant inhibition of EGF-stimulated DNA synthesis. The kinetics for the decrease of EGF binding by TCDD and benzo[a]pyrene (BP) were compared. Inhibition of EGF binding by BP was maximal by 24 hr, with 90% recovery of EGF binding apparent by 48 hr. In contrast, TCDD treatment for 72 hr was required to produce maximal inhibition, and no recovery was evident up to 10 day after removal of TCDD from the growth medium. The data indicate that modulation of EGF binding by TCDD was mediated by the Ah receptor. Subsequent cellular responses, for example, inhibition of EGF-stimulated DNA synthesis, may be important in the expression of altered differentiation patterns observed in human epidermal keratinocytes exposed to TCDD.     

Targeted delivery of vascular endothelial growth factor improves stem cell therapy in a rat myocardial infarction model

Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been successful because of poor cell survival due in part to insufficient blood supply after myocardial infarction (MI). We hypothesize that targeted delivery of vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes targeting overexpressed P-selectin in MI tissue were infused by tail vein immediately after MI. One week later, MSCs were injected intramyocardially. The cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC treatment. Targeted VEGF + MSC combination treatment showed highest attenuation in cardiac function loss. The combination treatment also increased blood vessel density (80%) and decreased collagen content in post-MI tissue (33%). Engraftment of MSCs in the combination treatment group was significantly increased and the engrafted cells contributed to the restoration of blood vessels.From the Clinical EditorVEGF immunoliposomes targeting myocardial infarction tissue resulted in significantly higher attenuation of cardiac function loss when used in combination with mesenchymal stem cells. MSCs were previously found to have poor ability to restore cardiac tissue, likely as a result of poor blood supply in the affected areas. This new method counterbalances that weakness by the known effects of VEGF, as demonstrated in a rat model.     

急性白血病异基因造血干细胞移植患者口腔护理体会

目的：在异基因造血于细胞移植过程中,患者很容易发生口腔黏膜的破溃、出血、感染,对原有口腔护理进行改进,并观察其效果。方法：对住院的6例异基因造血干细胞移植患者,采取正确的刷牙方式,护理人员每日评估刷牙的效果,认真观察牙齿的洁净,口腔有无出血、溃疡、炎症。结果：3例患者未发生口腔黏膜病变,1例口腔感染,2例溃疡（中度1例,轻度1例）,均无出血。结论：一般异基因造血干细胞移植的患者均为神志清楚、可自行活动的人群,采用口腔护理棉球擦拭方法,被动接受这种方式时患者有种无用感,从心理和生理上过度依赖医护人员,不利于树立战胜疾病的信心,从而使患者更难渡过以后不适阶段。改为刷牙式口腔护理,可以诱导患者积极配合治疗的意识,提升患者的精神状态,节省了工作时间,提高了工作效率,同时树立了患者战胜疾病的信心。     

碱性成纤维细胞因子在异基因外周血造血干细胞移植病人中的应用

目的研究b-FGF喷雾剂对异基因外周血造血干细胞移植病人口腔溃疡的影响.方法将34例进入血液层流室的异基因外周血造血干细胞移植病人随机分为实验组与对照组,分别观察口腔溃疡发生情况,愈合时间分布,平均愈合天数及病人口腔溃疡VAS疼痛评分.结果实验组与对照组的口腔溃疡发生率无明显差异,但口腔溃疡伪膜发生率,平均愈合天数及病人口腔溃疡VAS疼痛评分明显低于对照组.结论b-FGF可减少病人口腔溃疡伪膜的发生,使口腔溃疡面提前愈合,提高病人痛阈,降低病人疼痛感,以较好状态度过造血干细胞移植期.     

Effect of donor STAT4 polymorphism rs7574865 on clinical outcomes of pediatric acute leukemia patients after hematopoietic stem cell transplant

STAT4 polymorphism, rs7574865 is linked to various autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Its T minor allele is associated with higher STAT4 mRNA and protein expression, indicating a stronger skewed immune response than the norm. Although widely studied in autoimmune disease patients and the general population, its effect on immunocompromised subjects is still unknown. Especially in situations, i.e. post-hematopoietic stem cell transplantation (post-HSCT), where control of the immune response is crucial. Hence, this study investigates if the presence of the T minor allele in donors would affect immunological response and clinical outcomes post-HSCT. Samples from 161 pediatric patients who underwent allogeneic HSCT for acute leukemia and showed complete chimerism by donor cells were obtained. Six clinical outcomes were investigated; hepatic veno-occlusive disease, acute graft-vs-host disease, chronic graft-vs-host disease, cytomegalovirus (CMV) infection, relapse and overall survival. The TT genotype was found to be significant in the occurrence of CMV infection (P = 0.049), showing higher incidence of CMV infection compared to the others. Multivariate analysis confirmed that association of the TT genotype is independent from other variables in CMV infection occurrence (P = 0.010). This is the first study on STAT4 polymorphism rs7574865 in allogeneic HSCT as well as immunocompromised patients. As the TT genotype is associated with autoimmune diseases, our results seem at a paradox with current evidence hinting at a different role of STAT4 in normal circumstances versus immunocompromised patients. Further investigation is needed to elicit the reason behind this and discover novel applications for better post-transplant outcomes.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) modulates epidermal growth factor (EGF) binding to basal cells from a human keratinocyte cell line

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) modulates the proliferation, differentiation, or both, of epidermal keratinocytes in vivo and in culture. The growth of epidermal cells in culture is regulated by several biochemical mediators including epidermal growth factor (EGF). In this report the actions of TCDD on EGF binding in a basal cell population from a human keratinocyte cell line were examined. TCDD decreased the specific binding of 125I-EGF to basal cells by 40% within 96 hr. This reduction in EGF binding could not be attributed to changes in the state of differentiation as assessed by cell size and morphology, and cornified envelope competence, a marker of terminal differentiation. Modulation of EGF binding by TCDD was concentration-dependent (EC50 = 1 nM) and stereospecific, suggesting involvement of the Ah receptor. Scatchard analysis of EGF binding to the basal cells indicated a single class of high-affinity sites in both control (Kd = 0.14 nM) and treated (Kd = 0.11 nM) cultures and confirmed a decrease in the number of these sites in response to TCDD. The reduction in EGF binding correlated with a decrease in EGF-stimulated DNA synthesis and cell proliferation. Comparison of differentiation-competent squamous cell carcinoma (SCC) lines treated with TCDD supported an association between modulation of EGF binding and enhanced differentiation. The data indicate that basal cells are a target for TCDD. We propose that the modulation of EGF binding in basal keratinocytes by TCDD is one of the critical regulatory events resulting in enhanced differentiation.     

角质细胞生长因子对人工流产术后子宫内膜的修复作用及对月经转归、卵巢排卵的影响

目的探讨角质细胞生长因子( KGF)对人工流产术后子宫内膜的修复作用及对月经转归、卵巢排卵的影响。方法选取 2019年 12月至 2020年 12月在石家庄市人民医院行人工流产术的早孕妇女 120例,将所有孕妇按随机数字表法分为观察组 60例,对照组 60例,对照组采用玻璃酸钠治疗,观察组采用 KGF治疗,观察并统计两组的阴道出血天数和月经复潮时间,采用彩色多普勒超声诊断仪对两组子宫动脉阻力指数、血流量、搏动指数、收缩末期血流峰值 /舒张末期血流峰值( S/D)、平均流速血流动力学参数进行测评,采用腹部 B超检查两组的子宫内膜厚度变化情况,统计两组的卵巢恢复排卵例数。 B超检查两组的宫腔粘连程度。结果观察组阴道出血天数( 4.62±0.23)d和月经复潮时间( 28.12±2.06)d均短于对照组( 6.23±0.55)d、(34.12±2.16)d(P<0.05);治疗后,对照组阻力指数、搏动指数、血流量、平均流速、 S/D均显著降低( P<0.05),且观察组治疗后上述指标均高于对照组( P<0.05);观察组子宫内膜厚度( 9.36±1.09)mm大于对照组( 6.22±1.11)mm(P<0.05);观察组卵巢恢复排卵例数 22例多于对照组 6例( P<0.05);观察组宫腔粘连程度低于对照组(P<0.05)。结论 KGF治疗可有效改善人工流产术后月经转归情况,稳定术后血流动力学,促进子宫内膜修复和卵巢排卵功能的恢复。     

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia‐induced vascular leakage and oedema in rat brain

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia‐induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF‐A site were identified and validated with a Ramachandran plot. The active site residues of VEGF‐A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF‐A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O₂). Additionally, the best candidate molecule's efficacy was assessed in male Sprague‐Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor‐A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor‐A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib‐treated rats. Vascular endothelial growth factor‐A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia‐induced vasogenic oedema by regulating VEGF levels.     

血管内皮生长因子基质金属蛋白酶-9在口腔鳞状细胞癌中的表达及意义

目的探讨血管内皮生长因子(VEGF)和基质金属蛋白酶9(MMP-9)在口腔鳞状细胞癌(OS-CC)组织中的表达及临床意义。方法采用免疫化学Elivison两步法检测53例NSCLC组织、20例口腔正常黏膜组织中VEGF、MMP-9的表达,并对其与临床、病理特征的关系进行分析。结果 53例OSCC中VEGF、MMP-9的阳性率分别为50.9%、64.2%,和口腔正常黏膜组织相比较差异有统计学意义(P<0.05)。OSCC中VEGF、MMP-9的表达与患者的年龄、性别、病变部位无关,与肿瘤分期、组织学分级、淋巴结转移有关(P<0.05)。VEGF与MMP-9的表达呈正相关(r=0.446,P<0.01)。结论 VEGF、MMP-9在口腔鳞状细胞癌的发生、发展中起着重要作用,二者联合检测可为口腔鳞状细胞癌恶性程度和预后的判断提供有效证据。     

Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC‐4 cells

Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti‐cancer activities. Herein, we investigated the anti‐oral cancer activity of casticin on SCC‐4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca²⁺ production, levels of ΔΨ_m and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G₂/M phase arrest in SCC‐4 cells. Casticin promoted ROS and Ca²⁺ productions, decreases the levels of ΔΨ_m, promoted caspase‐3, ‐8, and ‐9 activities in SCC‐4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC‐4 cells. In conclusion, casticin decreased cell number through G₂/M phase arrest and the induction of cell apoptosis through caspase‐ and mitochondria‐dependent pathways in SCC‐4 cells.     

组织因子和基质金属蛋白酶-2在口腔鳞癌生长和转移中的作用

目的 研究人类口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中组织因子(tissue factor,TF)和基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)在肿瘤生长和转移中的作用及二者之间的关系.方法 收集口腔癌标本42例、正常口腔黏膜10例,采用免疫组化的方法检测TF和MMP-2的表达,并分析二者之间及其和肿瘤分期、淋巴结转移的关系.结果 口腔癌中TF和MMP-2的表达均较正常组织明显增加,口腔癌中TF和MMP-2的高表达和肿瘤的临床分期及淋巴结转移有关,同时二者的高表达存在一致性.结论 在口腔癌中TF和MMP-2关系密切,共同参与了肿瘤的生长和转移.     

肝细胞生长因子基因联合骨髓间充质干细胞治疗糖尿病周围动脉硬化闭塞症及糖尿病足近期观察

目的 探讨利用肝细胞生长因子(HGF)基因联合骨髓间充质干细胞治疗糖尿病周围动脉硬化闭塞症(PAD)和糖尿病足的临床疗效.方法 将Fontaine分级Ⅲ～Ⅳ级的糖尿病PAD及糖尿病足患者30例完全随机分为2组.研究组(16例)采用携带人HGF基因的质粒DNA( HGF-PVAX1 )4 mg联合骨髓动员后的于细胞,局部注射于患肢腓肠肌;对照组(14例)于患肢腓肠肌局部注射单纯骨髓动员后的于细胞.分别于移植术后1、3、6个月比较2组在干细胞局部注射治疗前后的临床疗效.结果 2组患者间歇性跛行有好转.研究组术前与术后6个月的下肢踝/肱指数(ABI)分别为(0.346±0.036)、(0.596±0.036),对照组是(0.379±0.031)、(0.468±0.032).2组术后与术前相比,差异均有统计学意义(均P＜0.05);术后研究组ABI水平高于对照组,差异亦有统计学意义(P＜0.05).研究组术后皮温平均为(35.9±1.8)℃,术前为(33.4±2.1)℃;对照组术后皮温平均为(33.1±1.3)℃,术前为(33.7±1.5)℃.2组皮温变化程度比较,差异有统计学意义(P＜0.05).2组移植后3个月复查下肢动脉彩色超声,股浅动脉、腘动脉未见明显变化.研究组移植前足背动脉血流量≥20 ml/min者8例,15 ～ 19 ml/min者4例,1～ 14 ml/min者2例,0 ml/min者2例;移植后≥20 ml/min者10例,15 ～ 19 ml/min者2例,1～14 ml/min者2例,0ml/min者2例.对照组移植前足背动脉血流量≥20 ml/min者6例,15～19 ml/min者3例,1～14 ml/min者3例,0ml/min者2例;移植后≥20 ml/min者7例,15～19 ml/min者2例,l～ 14 ml/min者3例,0 ml/min者2例.研究组移植后足背动脉血流量改善情况好于对照组,差异有统计学意义(P＜0.05).2组间不良反应发生率差异无统计学意义.结论 注射HGF-PVAXl联合骨髓干细胞移植可在一定程度上改善肢体缺血,可能成为治疗PAD的一种新手段.但其远期疗效和安全性还有待观察.     

Recombinant human erythropoietin suppresses endothelial cell apoptosis and reduces the ratio of Bax to Bcl-2 proteins in the aortas of apolipoprotein E-deficient mice

Recent clinical trials have raised concern that therapy with recombinant human erythropoietin (EPO) may increase cardiovascular disease risk, event rate, and mortality. Endothelial cell apoptosis has been implicated in both atherogenesis and in the destabilization and rupture of atheromatous plaques. In the current study, we observed that EPO and the EPO-mimetic peptide EMP-1 markedly suppressed lipopolysaccharide-induced apoptosis in endothelial cell monolayers. Therapeutic concentrations of EPO upregulated Bcl-2 expression and concurrently diminished expression of Bax, resulting in a net decrease in the ratio of Bax to Bcl-2 protein concentrations. In vivo studies demonstrated that EPO receptor is abundantly expressed in murine aorta and that EPO treatment for 10 weeks markedly decreased the ratio of Bax to Bcl-2 protein in the aortas of apolipoprotein E-deficient mice fed a high-fat diet. To our knowledge, these data are the first to reveal a modulation of regulators of the apoptotic pathway in murine aorta by chronic EPO treatment. These observations imply that long-term administration of EPO may have the potential to affect plaque stability.     

肺部铜绿假单胞菌感染前后肺组织角质细胞生长因子的变化研究

目的 针对肺部铜绿假单胞菌(PAE)感染前后肺组织角质细胞生长因子(KGF)的变化进行研究.方法 本次研究对象为本院2013年12月至2015年9月收治的60例肺炎患者.在患者发生感染前、感染后,对患者的肺组织标本进行收集,并进行感染前后患者KGF的检测,针对感染前后的KGF的变化进行观察比较.结果 在本次研究中,感染前KGF蛋白量为(1.02±0.02),感染后6h的含量为(1.23±0.14),感染后9h的含量为(1.54±0.13),感染后72 h的含量为(2.18±0.47),肺炎患者感染PAE前的KGF蛋白含量与感染后6h、感染后9h、感染之后72 h的KGF蛋白含量比较,P=0.000,差异有统计学意义.感染后6h的KGF蛋白含量与感染后9h、感染之后72 h的KGF蛋白含量比较,P=0.000,差异有有统计学意义.感染后9h后的KGF蛋白含量与感染之后72 h的KGF蛋白含量比较,P=0.000,差异有统计学意义.结论 针对肺炎患者,实施KGF变化的检测,可以有效地观察患者是否发生了肺部PAE感染,并为感染的控制和预防,提供有效的依据.     

Progressive multifocal leukoencephalopathy in a haploidentical stem cell transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone

JC virus (JCV) is a double-stranded DNA virus belonging to family Polyomaviridae. It causes progressive multifocal leukoencephalopathy (PML), mainly in immunosuppressed people. JCV had been shown to require the serotonin 2A receptor for host cell entry. We report a case of clinical, neuroradiological and virological response of biopsy-proven PML in a 33-year-old comatose woman after treatment with the anti-psychotic drug risperidone. Since risperidone is the tightest binding of current drugs to this receptor we think this may have blocked JCV entry in our patient, allowing her immune recovery and viral clearance.