Sclerotherapy in the U.S. Past, present, future.
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Biomedical subjects
Publications and source records attributed to R A Weiss.
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T cells reactive against immunodominant regions of inducible heat shock proteins (HSPs) have been identified in the chronic inflammatory lesions of several experimental autoimmune diseases. Since HSPs are known to be induced by a number of renal tubular epithelial cell toxins associated with chronic interstitial nephritis, we investigated the relevance of HSP expression and T cell reactivity to HSP70 in a model of progressive inflammatory interstitial nephritis. Chronic administration of cadmium chloride (CdCl2) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdCl2 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-alpha/beta+ T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdCl2-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdCl2-treated mice at a time when immunoreactive HSP70 is detectable in the kidneys, but before the development of interstitial mononuclear cell infiltrates. T cells isolated from the nephritic kidneys of mice treated with CdCl2 for 13 wk are also cytotoxic to heat shocked or cadmium-treated tubular cells. These kidney-derived T cells additionally induced interstitial nephritis after passive transfer, indicating their pathogenic significance. Our studies strongly support a role for HSP-reactive T cells in CdCl2-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "non-immune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.
Mouse, rat, rabbit, cat, and mink cell lines expressing human CD4 restrict entry of HIV-1 strains at the cell surface. We now report that CD4+ cat and rabbit cell lines are permissive to cell fusion induced by several HIV-2 and SIV strains. CD4+ rat and mouse cells are only sensitive to HIV-2 and SIV fusion in the presence of active amphotericin B. HIV-2 and SIV replicate in CD4+ cat and CD4+ mink cells, but not in the CD4+ rabbit, rat, or mouse cells. These latter cell lines poorly express a transfected DNA molecular clone of HIV-2 DNA. CD4+ rat cells are sensitive to entry by HIV-2 (HTLV-1) pseudotypes and also to HIV-2 if amphotericin B is present. Early reverse transcription then occurs without subsequent viral gene expression, but the fusion-sensitive CD4+ rabbit cells are not permissive for HIV-2 reverse transcription. Our observations demonstrate (i) that the cat and mink cell lines express everything required except human CD4 for entry and replication by several HIV-2 and SIV strains and (ii) that distinct postpenetration blocks to viral replication are evident in rabbit and rodent cell lines.
The HTLV-I producer cell line C10/MJ2 does not induce syncytium formation with HTLV-I receptor expressing cells. Here we show that this cell line produces a truncated envelope protein, which, because of a premature stop codon, lacks the hydrophobic membrane anchor domain of the transmembrane protein (TM). Despite lacking a membrane anchor this envelope protein is expressed on the cell surface and associated with released virions. However, its incorporation into virions seems less efficient than that of a full-length envelope glycoprotein and some of its released into the cell culture supernatant as soluble surface glycoprotein (SU)-TM complexes. Small amounts of such a truncated envelope glycoprotein were also found in the fusion-competent HTLV-I producer cell line MT2. Premature truncation of HTLV-I envelope proteins in producer cell lines may result from in vitro selection for a less fusogenic phenotype. The association of truncated HTLV-I envelope proteins with virions and cell surfaces may reflect interactions between the SU domain and cellular membranes, possibly with the cellular receptor for HTLV-I.
Varicose veins are superficial vessels that are abnormally twisted, lengthened, or dilated and are usually caused by inefficient or defective valves within the vein. They represent a medical condition accompanied by symptoms deserving treatment. Varicose veins are a manifestation of venous disease that may precede later severe complications. Varicosities cause cutaneous disease in addition to complications specific to the venous system. This article reviews the epidemiology, adverse sequelae, anatomy, pathophysiology, evaluation, and treatment of varicose veins.
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We have isolated a new foamy virus from blood samples taken from two apparently healthy orangutans (Pongo pygmaeus). The older orangutan has since died with encephalopathy after a brief acute illness, while the younger one, his grandson, remains well. These animals and 12 other orangutans had specific antibodies to foamy virus as measured by immunofluorescence. The new foamy virus and the antisera showed strong and specific neutralization, with only weak cross-reaction with other simian foamy virus strains. Southern blotting with gag and env probes of human foamy virus and PCR amplification showed that the new foamy virus, designated SFV-11, is related to, yet distinct from, previously characterized strains from humans, chimpanzees, and monkeys.
The inactivation of type C retroviruses by human serum may be a considerable impediment to the use of retroviral vectors in vivo for gene therapy. Here we show that virus inactivation is dependent both on the virus and on the cell line used to produce the virus. All viruses produced from murine NIH 3T3 or dog Cf2ThS+L- cells are sensitive to human serum. In contrast, those produced from mink Mv-1-Lu and human HOS or TE671 cells are at least partially resistant, with the exception of murine leukemia viruses. In particular, the feline endogenous virus RD114 is completely resistant to a panel of eight human sera when produced from Mv-1-Lu or HOS cells. This differential resistance is controlled by the viral envelope proteins. Virus inactivation can be correlated with the ability of the producer cells to be lysed by human serum. Inactivation of sensitive viruses requires the classical pathway of complement but does not require virion lysis.
As a rare, sporadic disease Langerhans cell histiocytosis (LCH) presents a difficult problem in defining a likely etiology. Epidemiological data would not a priori lead one to choose a viral etiology. However, there are rare tumours which occur as sequelae of common infections from Epstein-Barr virus or human papilloma viruses. Likewise some viruses can cause cells to elaborate cytokines which could ultimately stimulate Langerhans cell growth. There is only a small amount of experimental data testing the hypothesis that viruses might be associated with LCH. The theoretical constructs surrounding this question and new data refuting the association are summarised.
The basis of in-office evaluation of leg vascular disease involves Doppler ultrasound to estimate flow in arteries and veins. Arterial evaluation localizes sites of obstruction by segmental pressures obtained by Doppler signal assessment using pressure cuffs. Ankle compared with brachial arterial pressure is the most rapid screening test. Plethysmography permits more automated and sensitive analysis of pressure waveforms. Venous evaluation identifies sources of increased pressure transmitted by incompetent valves to surface veins causing varicosities and telangiectases. Doppler ultrasound permits sites of reverse flow (incompetent valves) to be localized, whereas plethysmography enables physiologic consequences of incompetent valves to be analyzed. Plethysmography with pressure cuff placement localizes deep system disease versus superficial disease, and rules out deep malfunction. When in-office diagnostic tests are equivocal, duplex ultrasound or more invasive tests should be considered.
Many questions have been posed about acquired immunodeficiency syndrome (AIDS) pathogenesis. Is human immunodeficiency virus (HIV) both necessary and sufficient to cause AIDS? Is AIDS essentially an autoimmune disease, triggering apoptosis, or is virus infection the cause of T helper lymphocyte depletion? What is the significance of HIV tropism and the role of macrophages and dendritic cells in AIDS? Is there viral latency and why is there usually a long period between infection and AIDS? Is HIV variation a crucial aspect of its pathogenesis and, if so, do virulent strains emerge? Although this article provides few definitive answers, it aims to focus commentary on salient points. Overall, it is increasingly evident that both the tropism and burden of HIV infection correlate closely with the manifestations of disease.
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The single copy endogenous retrovirus locus ERV-3 is known to be primarily expressed in the placenta. The absence of expression of this gene in choriocarcinoma cell lines has led to speculation that this may be a defect associated with this abnormality. We show here that ERV-3 is not normally expressed in the cytotrophoblast from which these tumour cells are derived but is expressed in normal syncytiotrophoblast. The conservation of the ERV-3 open reading frame for env in ape and old world monkey species and its tight regulation and site of expression suggest a functional role for this gene in this tissue.
It has been suggested that the V3 domain of human immunodeficiency virus type 1 (HIV-1) isolates has to interact with a cell-surface-associated or endosomal proteinase during virus entry into susceptible cells. To investigate this hypothesis, we examined the effect of several mutations in the V3 loop on its susceptibility to proteolytic cleavage by thrombin and cathepsin E and compared it with the effect of these mutations on viral infectivity. The data obtained indicate that, if an interaction between the V3 loop and a proteinase is indeed crucial for viral entry, the substrate requirements for such a proteinase(s) would have to be very complex. In particular, it seems unlikely that a single enzyme with a unique specificity would be able to interact with all of the different HIV-1 and HIV-2/SIV strains isolated so far. Therefore, one would have to postulate the involvement of several cellular proteinases, or proteases with multiple specificities, in V3-based viral tropism.
We have used Semliki Forest virus (SFV) vectors to express both the human immunodeficiency virus type 1 (HIV-1) envelope precursor gp160 and the cleaved external portion gp120. Expression of the foreign gene in this system is by transfection of recombinant SFV RNA, or by infection with a recombinant SFV virus that has a wide host range. pSFV1-gp120 or pSFV1-gp160 were expressed in baby hamster kidney (BHK) cells and two human cell lines: HeLa cervical carcinoma and MOLT-4 CD4+ T cells. After SFV1-gp120 infection of HeLa cells, 3.3 micrograms of gp120 was secreted into the media by 1 million cells in a 24-hr period. The secreted envelope glycoprotein was recognized by anti-gp120 monoclonal antibodies directed against both linear and conformation-dependent epitopes in different regions of the molecule. The recombinant gp120 also bound to a soluble form of the CD4 receptor. Syncytium formation was observed when MOLT-4 cells were infected with SFV1-gp160. The gp160 expressed by BHK cells induced syncytia during cocultivation with C8166 CD4+ T cells. These data indicate that SFV vectors can be used to produce the HIV-1 envelope glycoproteins to high levels, and that these proteins are correctly processed, folded, and transported to the cell surface. Furthermore, they exhibit functional activity as indicated by their ability to bind to soluble receptor and induce cell-to-cell fusion.
BACKGROUND: Facial telangiectasia is extremely common in patients with fair complexion. Electrosurgery has been the primary form of treatment in the past. OBJECTIVES: The authors retrospectively evaluated over 300 patients treated with sclerotherapy for facial telangiectasias. METHODS: Retrospective analysis of over 300 patients with facial telangiectasia treated with sclerotherapy and 55 facial spider telangiectasias treated with laser. RESULTS: Sclerotherapy utilizing hypertonic saline, Sclerodex, polidocanol, and sodium tetradecyl sulfate resulted in-between 50 and 100% resolution of facial telangiectasia with minimal complications. CONCLUSION: The treatment of facial telangiectasia should include sclerotherapy and laser treatment modalities, which effect a higher rate of clearance with less adverse sequela.
BACKGROUND: Treatment of varicose veins is directed towards eliminating sources of reflux causing venous hypertension in the superficial venous system. Doppler ultrasound is routinely used to localize sources of reflux prior to treatment of large varicose veins. OBJECTIVE: To assess the value of Doppler ultrasound in localizing reflux in subcutaneous reticular veins associated with groups of lateral thigh telangiectases. METHODS: Seven hundred patient records in which Doppler ultrasound was performed on thigh reticular veins were reviewed. Patients with reflux of the saphenofemoral junction, saphenopopliteal junction, or major saphenous system perforators were excluded. RESULTS: Audible reflux upon distal calf compression release was noted in thigh subcutaneous reticular veins of 618 out of 700 patients (88%). These incompetent reticular veins were associated with groups or webs of telangiectases and/or venulectases on the lateral thigh in almost all cases. Reflux was loudest just distal to the lateral femoral condyle. In 20 patients Doppler ultrasound was performed on a reticular vein while a telangiectasia associated with the reticular vein was injected with sclerosing solution. In 15 patients a clearly audible flow signal was heard in the reticular vein during injection. CONCLUSION: These findings indicate an association of telangiectatic veins with reticular veins on the thighs. Furthermore, this study underscores the value of Doppler in determining sources of reflux in smaller veins and implies that sclerotherapy of reticular veins is necessary for treatment of thigh telangiectatic webs.