Expression of alpha-defensin-1 in chronic hyperplastic candidosis

BACKGROUND: Chronic hyperplastic candidosis (CHC) represents a chronic opportunistic candida infection. We clarified the presence, localization and participation of alpha-defensin-1 in host response against chronic candidal stimulus. METHODS: Immunohistochemically stained CHC biopsies (n = 10) were compared to candida negative idiopathic leukoplakia (n = 10). RESULTS: In CHC alpha-defensin-1 was detected in neutrophils intravascularly, in lamina propria and in the epithelium, in part in intraepithelial microabscesses. Staining intensity of individual neutrophils varied and was associated with peri- and extracellular staining, in particular in the superficial epithelial cell layers. In controls only very few homogeneously staining neutrophils were detected intravascularly without any extracellular alpha-defensin-1 deposition. CONCLUSIONS: Neutrophils form microabscesses and respond to Candida by activation and release of alpha-defensin-1 to peri- and extracellular matrix. This together with the epithelial cell migration from the basal layer to epithelial surface leads to alpha-defensin-1 rich protective shield in the most superficial epithelial cell layers.     

食管癌患者血缘亲属及不同性别食管癌患病风险比较研究

目的 对比分析食管癌病例组与对照组血缘亲属食管癌患病风险,并了解食管癌家族中危险亲属人群患病的新线索.方法 采用病例对照研究方法 ,对食管癌病例组及对照组各720例进行逐层分析,以比较两组各血缘亲属父系、母系食管癌患病危险度(OR)的大小及差异.结果 (1)病例组Ⅰ级亲属食管癌患病危险度(1.34%～2.24%)显著高于对照组(0.78%～1.21%)(P＜0.01);Ⅰ级亲属中病例组父母亲食管癌患病危险度为6.11%,显著高于对照组父母亲食管癌患病危险度2.97%(P＜0O01).(2)以血缘亲属中父系和母系亲属逐层分析可见,病例组父系食管癌患病危险度(0.87%～1.01%)与母系患病危险度(0.50%～0.79%)均显著高于对照组父系食管癌患病危险度(0.53%～0.65%)与母系患病危险度(0.38%～0.47%)(P＜0.05).进一步分析显示,病例组父系中男性亲属与母系中女性亲属,即父系中祖父、父亲、叔伯食管癌患病危险度为2.68%与母系中外祖母、母亲、姨的食管癌患病危险度1.91%均显著高于对照组父系中男性亲属食管癌患病危险度1.50%与母系中女性亲属食管癌患病危险度0.92%(P＜0.01).结论 山西省食管癌患者血缘亲属发病危险主要是父亲及其兄弟、母亲及其姐妹,其下代患食管癌风险要大.     

Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10–45 years

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B^®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

Pharmacology of the internal anal sphincter and its relevance to faecal incontinence

1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence.     

Charcot-Marie-Tooth neuropathy type 1A combined with Duchenne muscular dystrophy

We report a 24-year-old male with an unusual combination of two inherited neuromuscular disorders – Charcot-Marie-Tooth (CMT) disease type 1A and Duchenne muscular dystrophy (DMD). A phenotypic presentation of this patient included features of both these disorders. Nerve conduction studies revealed demyelinating peripheral neuropathy. Electromyography showed a profound myogenic pattern. The serum creatine kinase level was highly elevated. Muscle biopsy revealed a dystrophic picture with deficient dystrophin immunostaining. CMT1A duplication on chromosome 17p11.2 was found. The frame-shift mutation c.3609–3612delTAAAinsCTT (p.K1204LfsX11) was detected in the dystrophin gene by analysing mRNA isolated from the muscle tissue. The patient inherited both these mutations from his mother. The combination of CMT1A and DMD has not been reported as yet.     

甲状腺癌淋巴结微转移的研究

目的:探讨MUC1检测在甲状腺癌淋巴结微转移的可靠性和敏感性。方法:对488例甲状腺疾病手术患者于术前24h用1%美兰1.0~2.0mL注射于甲状腺结节或周围腺体，术中显示蓝染淋巴结，采用RT-PCR法测定临床蓝染淋巴结中的MUC1。 结果:蓝染淋巴结显示率甲状腺癌为93%，良性病例为0。研究组80个蓝染淋巴结中发现有MUC1mＲＮＡ表达的为95%,与病理诊断率(86%)相比有提高（P<0.05）;良性病变（阴性对照组）淋巴结均不存在MUC1mRNA的表达;阳性对照组的癌转移性淋巴结均存在MUC1mRNA的表达。结论:MUC1较病理检查敏感，PCR产物点杂交进一步证实MUC1作为PCR标志物有较好的可靠性。     

川芎嗪对肾缺血再灌注时c-fos bcl-2 ICAM-1蛋白表达的影响

目的　探讨大鼠肾缺血再灌注损伤不同时间c -fos、细胞淋巴瘤 /白血病 - 2、细胞间粘附分子- 1蛋白的表达及川芎嗪对其影响。方法　用免疫组化法检测大鼠急性肾缺血再灌注不同时间内及川芎嗪干预后c -fos、细胞淋巴瘤 /白血病 - 2、细胞间粘附分子 - 1蛋白表达的分布及强度变化。结果　c -fos蛋白分布于近曲小管、远曲小管、集合管上皮细胞的细胞核、细胞浆内 ,再灌注后 1h表达明显增强 ,3h达高峰 ,6h锐减。细胞淋巴瘤 /白血病 - 2蛋白主要分布于近曲小管上皮细胞的细胞浆 ,再灌注后 1h表达明显增强 ,6h达高峰 ,2 4h仍有较强表达。细胞间粘附分子 - 1蛋白分布在肾血管、肾小管等部位 ,其中以肾血管为著 ,其表达增强于再灌注后 1h ,直到 2 4h仍有增高趋势。川芎嗪干预后c -fos、细胞间粘附分子 - 1蛋白表达明显下降 (P <0 0 1 )。细胞淋巴瘤 /白血病 - 2表达明显增高 (P <0 .0 1 )。结论　川芎嗪对肾缺血再灌注损伤有较好的保护作用     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.