Retrovirus receptors.
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Biomedical subjects
Publications and source records attributed to R A Weiss.
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To investigate the hypothesis that the human endogenous sequence ERV-3 has a function, we have cloned and expressed the transmembrane region of its envelope gene and raised specific antibodies to the fusion protein and to a synthetic peptide. These antibodies reacted with a 65-kDa polypeptide which constituted approximately 0.1% of the cellular protein in syncytiotrophoblasts in placenta. The evolutionary conservation and abundant expression of this endogenous retroviral protein in a specific cell type support the concept of a biological function. The similarity of a domain of ERV-3 env to putative immunosuppressive p15E sequences suggests that ERV-3 might form part of the placental immunosuppressive barrier between mother and foetus.
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Kaposi's sarcoma (KS), a vascular tumour that contains characteristic spindle cells forming slit-like spaces, may have an infectious aetiology. Recently, sequences of a new human herpesvirus, KSHV/HHV-8, have been identified in both HIV-associated and classical KS. We sought to identify the target cell of this virus in KS tumour tissue. Using PCR in situ hybridization (PCR-ISH) we show that KSHV/HHV-8 is present in the flat endothelial cells lining vascular spaces of KS lesions as well as in typical KS spindle cells. These findings show that KSHV/HHV-8 is present in the cell types thought to represent neoplastic cells in these lesions.
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BACKGROUND: Telangiectatic matting and hyperpigmentation are some of the most commonly observed side effects of sclerotherapy. Cutaneous necrosis is relatively rare and often of limited sequelae but most commonly related to extravasation of sclerosant. Physicians treating varicosities and telangiectasia by sclerotherapy must be familiar with causes and means for minimization of all three side effects. OBJECTIVE: This review article discusses the proposed etiology, risk factors, approach for minimizing, and suggested treatment for the three side effects of cutaneous necrosis, telangiectatic matting, and hyperpigmentation. RESULTS: Cutaneous necrosis may occur with the injection of any sclerosing agent even under ideal circumstances and does not necessarily represent physician error. When sclerosant extravasation occurs, dilution must occur immediately. Telangiectatic matting is a recognized complication occurring in approximately 15-20% of patients treated by sclerotherapy. Although the exact mechanism of the phenomena remains unknown, reactive inflammatory and/or angiogenic mechanisms are felt to play a role. Patients are advised that telangiectatic matting is usually not permanent and usually resolves spontaneously in 3-12 months. Postsclerosis pigmentation is defined as the appearance of persistent, increased pigmentation running the course of an ectatic blood vessel treated by sclerotherapy. The general incidence of hyperpigmentation ranges from 10 to 30%. Although hyperpigmentation may persist for months, its presence rarely deters patients from continuing treatment. Spontaneous resolution occurs in 70% at 6 months with 99% resolution occurring within 1 year. CONCLUSIONS: With understanding the etiology, risk factors, and ways to minimize these side effects our goal is to reduce their incidence. Attempting prevention may ultimately be the most effective means of treatment. Dermatol Surg 1995;21:19-29. LEARNING OBJECTIVES: After studying the following article, participant should be able to: 1. Understand the definition and potential causes of cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. 2. Advise patients prior to treatment on the common risks involved in sclerotherapy and to advise them on the relative incidence. 3. Understand the concept of minimal sclerosant concentration and how it can help the physician to choose sclerosing solution concentrations to minimize risks.
BACKGROUND: Doppler examination of varicosities is an essential part of accurate venous diagnosis prior to treatment. Doppler examination is the most fundamental of diagnostic techniques and must be familiar to all dermatologic surgeons treating the venous system of the leg. Those physicians presently concentrating primarily on telangiectasia will find their ability to judge when treatment will be effective greatly enhanced by Doppler-assisted diagnosis. OBJECTIVE: To describe the indications, basic principles, and a detailed, logical, rapid protocol for venous continuous wave Doppler examination. CONCLUSION: Continuous wave Doppler examination is a rapid, precise method to determine sources of reverse physiologic flow (reflux) prior to treatment of varicose and telangiectatic leg veins. Doppler-assisted mapping of physiologic abnormalities of the venous system should be the second step following physical examination.
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We have engineered ecotropic Moloney murine leukemia virus-derived envelopes targeted to cell surface molecules expressed on human cells by the N-terminal insertion of polypeptides able to bind either Ram-1 phosphate transporter (the first 208 amino acids of amphotropic murine leukemia virus surface protein) or epidermal growth factor receptor (EGFR) (the 53 amino acids of EGF). Both envelopes were correctly processed and incorporated into viral particles. Virions carrying these envelopes could specifically bind the new cell surface receptors. Virions targeted to Ram-1 could infect human cells, although the efficiency was reduced compared with that of virions carrying wild-type amphotropic murine leukemia virus envelopes. The infectivity of virions targeted to EGFR was blocked at a postbinding step, and our results suggest that EGFR-bound virions were rapidly trafficked to lysosomes. These data suggest that retroviruses require specific properties of cell surface molecules to allow the release of viral cores into the correct cell compartment.
In common with oncoviruses but unlike the lentivirus human immunodeficiency virus type 1, foamy (spuma) viruses require host cell proliferation for productive infection. We show that human immunodeficiency virus type 1 replicates in RD-CD4 cells regardless of the growth arrest condition of the cells, while murine leukemia virus is unable to infect growth-arrested RD-CD4 cells or cells progressing through a partial cell cycle that includes S phase but not mitosis. Human foamy virus, like murine leukemia virus, does not productively infect G1/S or G2 growth-arrested cells. Two other foamy viruses, simian foamy virus type 1, isolated from a macaque, and simian foamy virus type 6, isolated from a chimpanzee, also fail to establish productive infection in G1/S-arrested cells.
Novel retroviral protein expression constructs were designed to retain minimal retroviral sequences and to express dominant selectable markers by reinitiation of translation after expression of the viral genes. HT1080 cells were selected as producer cells for their ability to release high-titer viruses that are resistant to inactivation by human serum. Two HT1080-based packaging cell lines which produce Moloney murine leukemia virus cores with envelope glycoproteins of either amphotropic murine leukemia virus (FLYA13 line) or cat endogenous virus RD114 (FLYRD18 line) are described. Direct comparison with previous retroviral packaging systems indicated that 100-fold-higher titers of helper-free recombinant viruses were released by the FLYA13 and FLYRD18 lines.
The V3 loop of human immunodeficiency virus type 1 is both a determinant of viral cell tropism and a target for neutralizing antibodies. This relationship was investigated. Selection of a dual-tropic (T cells and macrophages) virus to replicate in CD4+ brain cells results in loss of macrophage tropism and of neutralization by an anti-V3 loop monoclonal antibody. Moreover, selection of the brain-selected variant to escape from V3 loop-specific neutralizing monoclonal antibodies results in the reduction or loss of brain cell tropism and the reacquisition of macrophage tropism. These data may indicate that the antigenic diversification of human immunodeficiency virus type 1 apparent after seroconversion can be selected either by immune responses or by colonization of new cell types.
The human immunodeficiency virus type 2 (HIV-2) strain LAV-2/B is able to infect a variety of human cell lines via a CD4-independent pathway. We have used the glycosylation inhibitors tunicamycin, swainsonine, and deoxymannojirimycin to further characterize this putative alternative receptor for HIV-2 (LAV-2/B). These antibiotics resulted in an increase (5- to 30-fold) in the susceptibility of a variety of CD4- human cell lines to infection by LAV-2/B (RD, HeLa, HT29, Rsb, Heb7a, Hos, and Daudi). Several nonprimate cell lines (mink Mv-1-lu, rabbit SIRC, hamster a23, mouse NIH 3T3, cat CCC, and rat HSN) remained resistant to infection by LAV-2/B after treatment with glycosylation inhibitors, suggesting that they do not express the HIV-2 CD4-independent receptor. Two of these nonprimate cell lines are readily infected by HIV-2 when they express CD4 (Mv-1-lu and CCC). Treatment of human cells with neuraminidase had no effect on subsequent infection by LAV-2/B, suggesting that the increase in susceptibility to infection of deglycosylated cells is not due to a change in the electrostatic charge of the cell surface. Treatment of RD CD4- cells and HeLa CD4+ cells with a variety of proteases resulted in a 75 to 90% decrease in infection by LAV-2/B when compared with untreated cells. Taken together, all these data suggest that HIV-2 can utilize a membrane glycoprotein other than CD4 to attach and fuse with a variety of human cells.
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BACKGROUND: The usual method of injection of sclerosing agents is based simply on clinical recognition and visualization of the varicose vein. OBJECTIVE: The authors present an original technique for sclerosing injections, named Doppler sclerotherapy. The purpose is to allow more accurate sclerotherapy in situations where varicose veins (usually greater than 4-5 mm) are not palpable in the supine position, but palpable when standing. METHODS: This technique consists of injecting the sclerosing agent using an uncomplicated continuous wave Doppler, a syringe, and a needle, according to a method consisting of four well-defined steps ensuring avoidance of arterial vessels and constant appreciation of the varicose vein to be treated, even during the injection. It requires no assistants and allows the treating physician's gaze to remain at the injection site while listening for very specific Doppler sounds of aspiration and injection. RESULTS: In our multicenter study of 220 patients (approximately 1,400 injections) all but 18 injections were successful for intravascular localization. No serious complications were noted. CONCLUSIONS: The principal indication is the treatment of varicose veins that are palpable while standing but impalpable in the supine position. In addition varicose veins in the groin region, lower third of the thigh, and along the axis of the small saphenous vein may be treated with this technique. In these situations it is a more accessible, faster, and economical technique, although it does not replace duplex ultrasound-guided injections.
Although venous systems are inherently variable, the treatment of varicose and telangiectatic leg veins can be approached in a logical, systematic fashion (Table 4). Instead of randomly injecting as many veins as possible in a given period of time, venous regions or entire abnormal superficial venous networks related to incompetent perforators should be injected in a single session. Although each patient requires differing amounts of time with this systematic approach, with experience, accurate estimations can be made, ensuring optimal productivity. Understanding the interconnected character of the venous system, it is senseless for physicians to limit treatment to telangiectatic veins. Dermatologists with an interest in phlebology should strive to perceive veins as a complete system, with the dermal telangiectatic component not as a separate skin disorder but as a manifestation of venous hypertension. An awareness of this will allow us to render optimal care for our patients.