Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

Status of vaccine research and development of vaccines for herpes simplex virus

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

一氧化氮合酶在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达

目的：检测诱导型和内皮型一氧化氮合酶（iNOS 和eNOS）在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达。方法：采用免疫组织化学SABC法检测iNOS和eNOS在30例外阴慢性单纯性苔藓蜡块（LSC）、30例外阴硬化性苔藓蜡块（LS）和10例外阴正常皮肤中的表达，并以人原始造血细胞抗原（CD34）标记微血管内皮细胞，测量各组织的微血管密度（MVD）。结果：iNOS和eNOS在外阴正常皮肤中无表达；在LSC中iNOS和eNOS每视野平均阳性细胞数分别为14.83±3.79和17.86±4.82，高于LS的8.00±3.35和6.43±3.87，差异均有统计学意义（P＜0.05）；在LSC和正常皮肤中MVD分别为21.58±2.48和20.44±3.66，高于LS（10.34±2.83）。iNOS和eNOS的表达具有明显的正相关性（Kappa=0.811，P＜0.05）。结论：iNOS和eNOS可能与LSC炎症过程中的血管扩张有关；在LS皮损真皮中微血管减少，iNOS和eNOS可代偿性地改善LS的血液循环。     

腺病毒介导的HSV—tk基因治疗大鼠脑胶质瘤实验研究

目的：带有ＨＳＶ－ｔｋ基因的重组腺病毒（ＡｄＨＣＭＶ－ｔｋ）结合核苷类似物（ＮＡ）治疗大鼠Ｃ６脑胶质瘤。方法：用Ｘ－ｇａｌ染色测定ＡｄＨＣＭＶ－ｌａｃＺ转染大鼠Ｃ６胶质瘤细胞的效率。用ＡｄＨＣＭＶ－ｔｋ／ＡＣＶ、ＧＣＶ离体及活体治疗大鼠Ｃ６胶质瘤。结果：ＡｄＨＣＭＶ－ｌａｃＺ感染Ｃ６细胞效率达１００％，ＡｄＨＣＭＶ－ｔｋ感染Ｃ６细胞，在病毒感染复数为１０００时，ＧＣＶ和ＡＣＶ半致死剂量分别为３μｇ／ｍｌ和２０μｇ／ｍｌ，Ａｄ－ＨＣＭＶ－ｔｋ／ＡＣＶ治疗大鼠Ｃ６胶质瘤模型，大鼠生存期超过９０天，而对照组分别为１７．０±１．６天（生理盐水组）、１４．５±１．３天（ＡｄＨＣＭＶ－ｌａｃＺ组），Ｐ＜０．００１。结论：重组腺病毒对靶细胞感染效率可达１００％，ＡｄＨＣＭＶ－ｔｋ用ＧＣＶ的杀伤Ｃ６胶质瘤细胞比ＡＣＶ强，而ＨＳＶ－ｔｋ／ＡＣＶ用腺病毒介导治疗大鼠脑肿瘤疗效显著。     

Herpes simplex virus latency in the nervous system – a new model

Permissive herpes simplex virus (HSV) infection in tissue culture results in host cell destruction. Latent HSV infection in vivo occurs in neurons of peripheral sensory ganglia (PSG) and it therefore can not take place in neurons in which the virus has completed a lytic replication cycle similar to that present in vitro. Our hypothesis, based on experimental data and observations in humans, suggests that establishment of latent infection and reactivation of HSV-1 does not involve neuronal cell loss. Latency is established in neurons in which the virus does not replicate and is determined, in part, by the tissue levels of a herpes transactivating protein (Vmw65) that is a component of the viral tegument. We also suggest that reactivation of latent infection does not involve destruction of neurons and is due to replication of virus at the peripheral mucocutaneous tissues to where virus or viral DNA have been transported from the nervous tissue. Alternatively, reactivation is initiated in the PSG using a replication cycle which does not involve irreversible damage to neurons. This model explains the lack of damage to neurons which continue to serve as permanent reservoirs of latent virus for the entire life of the host.     

单纯疱疹病毒感染与冠心病急性心肌梗死血液流变特性的相关性研究

目的　探讨单纯疱疹病毒 (HSV)感染与冠心病心肌梗死的关系。方法　测定 5 1例急性心肌梗死 (AMI)和 4 2例陈旧性心肌梗死 (OMI)患者及 31例冠脉造影正常者 (NC)的HSV - 1特异性抗体 (HSV - 1IgG、HSV - 1IgM)浓度 ,并同步观察纤维蛋白原 (Fg)、血液流变特性指标变化及其与HSV - 1感染的相关性。结果　AMI组HSV - 1IgG阳性率及平均浓度明显高于NC组 (P <0 0 5 ) ,HSV - 1DNA检测结果与之吻合。校正冠心病危险因素前后HSV - 1IgG阳性与AMI均有相关关系 (OR4 2 6 6 ,P =0 0 19;OR 3 82 1,P =0 0 32 )。AMI组IgG、Fg、血浆黏度、低 /高切全血黏度、红细胞压积、红细胞聚集指数高于 ,而红细胞变形指数低于NC组及OMI组 (P均 <0 0 5 )。AMI组中HSV - 1( )组上述指标 (除HCT外 )的改变与同组中HSV - 1( - )组及与NC、OMI组中HSV - 1( )组比较有显著性差异 (P均 <0 0 5 ) ,AMI组中HSV - 1( )组IgG与Fg、血浆黏度、低 /高切全血黏度、红细胞聚集指数呈正相关 ,而与红细胞变形指数呈负相关 ,调整冠心病的危险因素前后IgG与Fg均呈正相关。结论　HSV - 1感染与CHD(AMI)之间存在明显的相关性 ,与Fg、血液流变特性指标也存在相关性。     

Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005. Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American Cancer Society (Yuman Fong).     

Naturally occuring antibodies against nerve growth factor in human and rabbit sera: comparison between control and herpes simplex virus-infected patients

Antibodies against nerve growth factor (NGF) in sera were detected by enzyme-linked immunosorbent assays (ELISA), by their isolation after passage of sera through NGF immunoadsorbent columns and by their specificity to bind and immunoprecipitate mouse NGF as well as to stain by immunohistochemical methods cellular sites of NGF synthesis. Increased levels of anti-NGF antibodies were found in sera of herpes simplex virus (HSV)-infected patients but not in HSV-inoculated rabbits. As HSV latency is known to be promoted by NGF in vitro, these results may suggest that anti-NGF antibodies modulate the cytokine function of NGF and thus might play a role in HSV infection. The biological function of circulating antibodies against NGF, in general, is now open to future investigation.     

Clinical and histopathological findings of ''psoriatic neurodermatitis'' and of typical lichen simplex chronicus

BACKGROUND: We have seen several patients with itchy lichenified plaques located bilaterally on the elbows and/or knees and have named this condition 'psoriatic neurodermatitis' (PN). OBJECTIVE: The purpose of this study was to compare clinical and histopathological characteristics of these patients to those of patients with typical lichen simplex chronicus (LSC). METHODS: Nineteen patients with PN and 34 patients with typical LSC were included. Besides clinical dermatological evaluation, the prick test was carried out on 49 patients; the Phadiatop test on 40 patients; the patch test with European standard series on 47 patients; histopathological evaluation on 39 patients; and clinical psychiatric examination on 38 patients. RESULTS: Almost exclusively, PN was seen in females and was located on the extremities. It caused more plaques than typical LSC did. In PN, the plaques were smaller, sharper, more keratotic and less excoriated, and had fewer lichenoid papules around them. Itching was usually more severe in the evening, while resting and in a hot environment in typical LSC, but not in PN. In plaques of PN, microabscesses in the horny layer, hypogranulosis, regular acanthosis and thinning of the suprapapillary plates were more frequent, and hyperpigmentation in the basal layer was less. In patients with PN, depressive disorder was found more frequently; and generalized anxiety disorder or psychosomatic characteristics, less. There were no significant differences in the results of prick, Phadiatop and patch tests between patients with PN and those with typical LSC. CONCLUSION: In our opinion, it is most likely that the so-called PN is itchy psoriasis superimposed by LSC.