Genital and perianal herpetic ulcers are common in HIV-infected patients and chronic mucocutaneous ulcers persisting for more than 1 month are the hallmark of active AIDS status. However, atypical clinical manifestations of herpes simplex virus (HSV) may occur in immunocompromised patients presenting as tumor-like nodules or condylomatous or hypertrophic lesions, rather than a classic ulcer. Such unusual presentations raise the risk of misdiagnosis and a delay in appropriate treatment. Here we describe nine immunocompromised HIV-positive patients with CD 4 count ranging from 14-362/mm(3) (mean 170/mm(3)), with unusual tumoral presentation of anogenital herpes. There were six male and three female patients with AIDS with mean duration of HIV infection of 14 years. All of the patients had history of highly active antiretroviral therapy (HAART), with five patients compliant with the therapy at the time of biopsy. Six patients presented with scrotal or vulvar masses and three with perianal nodules. Five patients had adjacent human papilloma virus (HPV)-related lesions. Prior to excision, herpetic lesion was clinically suspected in only three patients and in the rest of the patients a malignant growth was the main clinical concern. The predominant histopathologic finding was dense dermal plasmacytic infiltration with overlying pseudoepitheliomatous hyperplasia, superficial ulcers and classic herpetic inclusions. Patients with AIDS may experience excessive number and size of both primary and reactivated herpetic lesions. The tumoral presentations discussed here are less common, but are often clinically misdiagnosed. It is important to be aware of these unusual presentations to provide a correct diagnosis and prompt, effective treatment for HSV. Several studies suggest that aggressive treatment of HSV in combination with HAART therapy provides a significant survival benefit. Pathobiology mechanisms of unusual and exaggerated tumor-like inflammatory response are not completely elucidated.

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Human herpesvirus-8 (HHV-8) latency-associated nuclear antigen (LANA) is expressed in endothelial and spindle cells of nearly all Kaposi sarcomas, and the presence of this antigen in serum is strongly correlated with the risk of developing Kaposi sarcoma in immunocompromised individuals. Studies of vascular tumors occurring in the general population show LANA expression to be specific for Kaposi sarcoma. No study to date, however, has examined whether non-Kaposi sarcoma vascular tumors arising in immunocompromised patients may express LANA, possibly reflecting origin from an HHV-8-infected endothelial progenitor cell. The objective of this study was to evaluate the specificity of LANA expression for Kaposi sarcoma in immunocompromised patients by LANA immunohistochemistry and real-time polymerase chain reaction (PCR) for HHV-8. A total of 13 cases of non-Kaposi sarcoma vascular tumors (12 hemangiomas and one epithelioid hemangioendothelioma) and 24 cases of Kaposi sarcoma, all from known HIV-positive patients, were immunostained for LANA and evaluated for the presence of HHV-8 DNA by real-time PCR. LANA expression was seen in 22 of 24 (92%) of Kaposi sarcoma cases and in 0 of 13 non-Kaposi sarcoma cases. Real-time PCR detected HHV-8 in all of the Kaposi sarcoma cases and in four of the non-Kaposi sarcoma cases (all hemangiomas). LANA expression appears to be a highly sensitive and specific marker of Kaposi sarcoma in both the general population and in HIV-positive patients. This is in contrast to HHV-8 PCR, which is positive in a small subset of non-Kaposi sarcoma vascular tumors, most likely due to detection of HHV-8 within intratumoral blood mononuclear cells by the highly sensitive real-time PCR technique. For this reason, LANA immunohistochemistry is preferable to HHV-8 PCR for the evaluation of problematic vascular proliferations in HIV-positive individuals.

Objective: The goal of this study was to develop, implement, and test an automated decision system to provide early detection of clinically important bronchopulmonary events in a population of lung transplant recipients following a home monitoring protocol. Subjects and Methods: Spirometry and other clinical data were collected daily at home by lung transplant recipients and transmitted weekly to the study data center. Decision rules were developed using wavelet analysis of declines in spirometry and increases in respiratory symptoms from a learning set of patient home data and validated with an independent patient set. Results: Using forced expiratory volume in 1 s or symptoms, the detection captured the majority of events (sensitivity, 80-90%) at an acceptable level of false alarms. On average, detections occurred 6.6-10.8 days earlier than the known event records. Conclusions: This approach is useful for early discovery of pulmonary events and has the potential to decrease the time required for humans to review large amount of home monitoring data to discover relatively infrequent but clinically important events.

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Transgenic mouse models are valuable resources for analyzing functions of genes involved in human diseases. Mouse models provide critical insights into biological processes, including in vivo visualization of vasculature critical to our understanding of the immune system. Generating transgenic mice requires the capture and modification of large-insert DNAs representing genes of interest. We have developed a methodology using a yeast-bacterial shuttle vector, pClasper, that enables the capture and modification of bacterial artificial chromosomes (BAC)-sized DNA inserts. Numerous improvements and technical advances in the original pClasper vector have allowed greater flexibility and utility in this system. Examples of such pClasper mediated gene modifications include: Claspette-mediated capture of large-insert genomic fragments from BACs-human polycystic kidney disease-1 (PKD1); modification of pClasperA clones by the RareGap method-PKD1 mutations; Claspette-mediated modification of pClasper clones-mouse albumin-1 gene; and, of most relevance to our interest in lymph node vasculature-Claspimer-mediated modification of pClasper clones-high endothelial venule and lymphatic vessel genes. Mice that have been generated with these methods include mice with fluorescent high endothelial venules.

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