Search PubMed⌕ Search

Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 91 records · Page 5Linked to original sources

Transillumination mapping prior to ambulatory phlebectomy.

BACKGROUND: Ambulatory phlebectomy (AP) for removal of varicose and reticular veins has become a very popular and widely used in-office outpatient technique over the past decade. One of the major obstacles of this or any other surgical vein removal technique is the technical difficulty presented to the surgeon by the disappearance of the veins to be removed when the patient is positioned horizontally on an operative table. Preoperative marking is therefore essential. OBJECTIVE: To investigate whether use of transillumination would facilitate and enhance marking of varicose veins prior to AP, we performed a study in which both traditional marking with the patient standing and transillumination marking with the patient horizontal were performed sequentially. METHODS: One hundred patients were sequentially examined prior to AP. The veins to be removed were mapped by the traditional way utilizing visual inspection and palpation in a standing position. They were then mapped in the supine or prone position utilizing a transillumination device specifically designed to enhance visualization of veins prior to venipuncture. RESULTS: In 100 out of 100 patients the markings performed using transillumination mapping most closely correlated with actual vein position during surgery. In addition, transillumination allowed for gauging of vein depth. CONCLUSIONS: Transillumination mapping significantly enhances the technique of ambulatory phlebectomy by more accurately visualizing the course of a varicose vein prior to extraction. Furthermore, sites for incisions or punctures are more accurately guided. As a result of this experience, it is now our routine practice to perform preoperative mapping for AP by transillumination in the horizontal position.

Ambulatory Surgical Procedures↗

Host range and interference studies of three classes of pig endogenous retrovirus.

Recent interest in the use of porcine organs, tissues, and cells for xenotransplantation to humans has highlighted the need to characterize the properties of pig endogenous retroviruses (PERVs). Analysis of a variety of pig cells allowed us to isolate and identify three classes of infectious type C endogenous retrovirus (PERV-A, PERV-B, and PERV-C) which have distinct env genes but have highly homologous sequences in the rest of the genome. To study the properties of these env genes, expression plasmids for the three env genes were constructed and used to generate retrovirus vectors bearing corresponding Env proteins. Host range analyses by the vector transduction assay showed that PERV-A and PERV-B Envs have wider host ranges, including several human cell lines, compared with PERV-C Env, which infected only two pig cell lines and one human cell line. All PERVs could infect pig cells, indicating that the PERVs have a potential to replicate in pig transplants in immunosuppressed patients. Receptors for PERV-A and PERV-B were present on cells of some other species, including mink, rat, mouse, and dog, suggesting that such species may provide useful model systems to study infection and pathogenicity of PERV. In contrast, no vector transduction was observed on nonhuman primate cell lines, casting doubt on the utility of nonhuman primates as models for PERV zoonosis. Interference studies showed that the three PERV strains use receptors distinct from each other and from a number of other type C mammalian retroviruses.

Animals↗

Packaging of endogenous retroviral sequences in retroviral vectors produced by murine and human packaging cells.

Interaction of retrovirus vectors and endogenous retroviruses present in packaging cell lines and target cells may result in unwanted events, such as the formation of recombinant viruses and the mobilization of therapeutic vectors. Using sensitive reverse transcriptase PCR assays, we investigated human and murine gene therapy packaging cell lines for incorporation of endogenous retrovirus transcripts into murine leukemia virus (MLV) vector particles and, conversely, whether vector genomes are incorporated into human endogenous retrovirus (HERV) particles. VL30 endogenous retrovirus sequences were efficiently packaged in particles produced by the murine AM12 packaging system. For every seven MLV-derived beta-galactosidase (beta-Gal) vector genomes present in the particles, one copy of VL30 was also packaged. Although human FLY packaging cells expressed several classes of HERV transcripts (HERV-K, HuRT, type C, and RTVL-H), none was detectable in the MLV vector particles released from the cells. Nonspecific packaging of the MLV Gag-Pol expression vector transcripts was detected in the FLY virions at a low level (1 in 17,000 sequences). These findings indicate that human packaging cells produce retrovirus particles far less contaminated by endogenous viral sequences than murine packaging cells. Human teratocarcinoma cells (GH cells), which produce HERV-K particles, were transduced with an MLV-derived beta-Gal vector. Although both HERV-K and RTVL-H sequences were found in association with the particles, beta-Gal transcripts were not detected, indicating that HERV Gag proteins do not efficiently package MLV-based vectors.

Animals↗

Update on childhood urinary tract infections and reflux.

Urinary tract infections (UTIs) are a common and potentially serious source of morbidity in infants and children. In the absence of identifiable structural and/or functional abnormality of the urinary tract that would predispose to UTI, such as vesicoureteric reflux (VUR), significant and permanent injury to the renal parenchyma (pyelonephritic scarring) from UTI is uncommon. However, those patients with such predisposing conditions are at risk for adverse long-term outcomes of pyelonephritic scarring such as hypertension and/or impairment of glomerular filtration rate (GFR). Although the acute symptomatology usually responds promptly to proper antibiotic therapy, the treating physician must be concerned with a number of intermediate and long-term health outcomes. Specifically, is bacteriuria associated with renal parenchymal inflammation? If so, will it heal with restoration of normal architecture (and function), or will there be replacement of formerly healthy renal tissue with fibrosis? How can future UTIs, each with their attendant risk of pyelonephritic scarring, be prevented? What combination of initial diagnostic tests and follow-up management are best suited for which patients to minimize such adverse outcomes? The approach to the diagnostic evaluation for structural and functional disturbances in the urinary tract that would predispose to UTI has evolved to answer these questions. This review will focus on the recent advances in the detection and management of uropathology associated with UTI, particularly that of vesicoureteral reflux (VUR).

Causality↗

Detection of SV40 sequences in human mesothelioma.

The presence of SV40 DNA sequences in British cases of mesothelioma was investigated using previously reported PCR assays. Three different SV40 primer sets were used which gave positive detection rates of 100% (SV.for3/SV.rev), 42% (PYV.for/rev) and 15% (SV.for2/SV.rev). When 26 mesothelioma biopsies were tested. Negative samples included 22 semen samples from AIDS patients, 10 blood donor DNAs and the human mesothelioma cell line H-MESO-1. The problems encountered with these assays and the interpretation of the results are discussed.

Base Sequence↗

KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma. The KSHV gene ORF K9 encodes vIRF which is a protein with low but significant homology to members of the interferon (IFN) regulatory factor (IRF) family responsible for regulating intracellular interferon signal transduction (Moore PS, Boshoff C, Weiss RA and Chang Y. (1996). Science, 274, 1739-1744). vIRF inhibits IFN-beta signal transduction as measured using an IFN-responsive ISG54 reporter construct co-transfected with ORF K9 into HeLa and 293 cells. vIRF also suppresses genes under IFN regulatory control as shown by inhibition of the IFN-beta inducibility of p21WAF1/CIP1, however, no direct DNA-binding or protein-protein interactions characteristic for IRF repressor proteins were identified. Stable transfectant NIH3T3 clones expressing vIRF grew in soft agar and at low serum concentrations, lost contact inhibition and formed tumors after injection into nude mice indicating that vIRF has the properties of a viral oncogene. Since vIRF is primarily expressed in KSHV-infected B cells, not KS spindle cells, this study suggests that vIRF is a transforming oncogene active in B cell neoplasias that may provide a unique immune escape mechanism for infected cells. This data is consistent with tumor suppressor pathways serving a dual function as host cell antiviral pathways.

3T3 Cells↗

Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines.

Unique among known human herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) encodes chemokine-like proteins (vMIP-I and vMIP-II). vMIP-II was shown to block infection of human immunodeficiency virus-type 1 (HIV-1) on a CD4-positive cell line expressing CCR3 and to a lesser extent on one expressing CCR5, whereas both vMIP-I and vMIP-II partially inhibited HIV infection of peripheral blood mononuclear cells. Like eotaxin, vMIP-II activated and chemoattracted human eosinophils by way of CCR3. vMIP-I and vMIP-II, but not cellular MIP-1alpha or RANTES, were highly angiogenic in the chorioallantoic assay, suggesting a possible pathogenic role in Kaposi's sarcoma.

Animals↗

Role of the amino-terminal extracellular domain of CXCR-4 in human immunodeficiency virus type 1 entry.

We have studied the role of the N-terminal extracellular domain of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CXCR-4, in the entry and fusion of syncytium-inducing strains of HIV-1. Progressive deletions were introduced in the N-terminal extracellular domain of CXCR-4 and the effect on infection by different isolates was tested. Infection of cells expressing the different CXCR-4 deletion mutants by HIV-1 LAI and 89.6 was reduced only about twofold. In contrast, the HIV-1 GUN-1 and RF isolates were substantially more impaired in their ability to mediate cell-free infection and cell-cell fusion. Since LAI and RF are T-cell line-tropic viruses while 89.6 and GUN-1 are dual tropic, no clear correlation between tropism and requirements for CXCR-4 N-terminal sequences emerged. We also introduced point mutations at the two N-linked glycosylation sites. The isolates tested (LAI, RF, GUN-1, and 89.6) were not affected by the removal of predicted N-linked glycosylation sites in CXCR-4. We conclude that distinct virus strains interact differently with the CXCR-4 coreceptor and that the N-terminal extracellular domain is not the sole functional domain important for HIV-1 entry.

Amino Acid Sequence↗

CD4-independent infection by HIV-2 (ROD/B): use of the 7-transmembrane receptors CXCR-4, CCR-3, and V28 for entry.

We have assayed a variety of 7tm chemokine receptors (CCR-2b, CCR-3, CCR-4, CCR-5, CXCR-1, CXCR-4) and two orphan 7tm receptors (V28 and EBI.1) for their ability to allow infection of CD4-negative feline kidney CCC cells by the HIV-2 strains ROD/A and ROD/B. We found that ROD/B was able to use CXCR-4 transiently expressed in CCC cells, and infection by ROD/A was enhanced 15-fold in the presence of sCD4. Feline CCC cells also became permissive to ROD/B and ROD/A entry when transiently transfected with the chemokine receptor CCR-3 or the orphan 7tm receptor V2B, when cultured in the presence of sCD4. Entry of ROD/A into CCC cells expressing CCR-3 could be blocked by 800 ng/ml eotaxin, the natural ligand for CCR-3.

Animals↗

Human retrovirus-5 proviral DNA is rarely detected in salivary gland biopsy tissues from patients with Sjögren's syndrome.

OBJECTIVE: To examine whether human retrovirus-5 (HRV-5) infection is associated with Sjögren's syndrome. METHODS: Salivary gland DNA was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Rigorous precautions were taken to prevent false-positive results from PCR contamination. Positive samples were confirmed by testing with an additional independent set of primers and were then sequenced. RESULTS: Ninety-two samples were examined (55 from Sjögren's syndrome patients, 37 from non-Sjögren's syndrome patients), 2 of which were positive. One was from a patient who had sicca symptoms but who did not satisfy the criteria for a diagnosis of Sjögren's syndrome. The other was from a patient with secondary Sjögren's syndrome. Owing to the extremely low virus load in minor salivary glands, the number of HRV-5-infected patients may be underestimated. In total, 3 different sequences of HRV-5 were identified which were 98% identical to the original sequence but which displayed variations between and within individuals. CONCLUSION: This is the first study to systematically seek a disease association with HRV-5, although with this method, an association with Sjögren's syndrome was not identified.

Amino Acids↗

Delayed acute renal failure in post-transplant period in young children from unexplained etiology.

This report describes six young children (5 male) who developed delayed acute renal failure (DARF) in the early post-kidney-transplant (Tx) period in the absence of acute rejection (AR) or other diagnosable conditions. These young children, aged 16.5 +/- 3.1 (12-21) months [mean +/- SD, (range)] and weighing 8.5 +/- 1.7 (7.1-11.4) kg received a primary renal Tx (5 living-related donor, 1 cadaver) between 1984 and 1992. Immunosuppression included prednisone, azathioprine, and Minnesota antilymphocyte globulin (MALG, n = 5); one patient received cyclosporine and no MALG. Initially, all patients had good urine output (UO). They became systemically ill and abruptly developed diminished UO on post-operative day (POD) 6.5 +/- 1 (4-8). DARF was accompanied by fever (39.1-40.4 degrees C, n = 6), thrombocytopenia (platelets < 100,000/mm3, n = 6), leukocytosis, or leukopenia (white cell count > 20,000/mm3, n = 4 or < 1,000/mm3, n = 1). Four patients had diarrhea. Three had ascites and one was surgically explored for suspected urinary leak. None showed significant urinary obstruction by renal ultrasound. Renograms showed intact blood flow. Renal biopsy showed tubular ectasia (n = 6), vascular congestion (n = 5), focal glomerular endothelial swelling (n = 4), and capillary thrombi (n = 3). None showed AR. Five patients required dialysis for 11 +/- 4 (7-15) days. All patients survived. One patient, treated for suspected AR with the monoclonal antibody OKT3, developed shock and lost her graft on POD 12 due to vascular thrombosis. Renal functional recovery in the remaining five patients took 14 +/- 5 (6-20) days and their serum creatinine at discharge was 0.7 +/- 0.5 (0.3-1.6) mg/dl. We report DARF from undetermined etiology occurring in the first 2 weeks of renal Tx in young children. Treatment is supportive care including dialysis. Recognition of this complication will help avoid risky investigations or unnecessary treatment for rejection.

Acute Kidney Injury↗

Our retroviral heritage.

Darwin could not have foretold that we are descended from viruses as well as from apes. While there is clear evidence that viral diseases, such as polio and rabies, affected ancient civilizations, viruses were not defined until the early years of this century, shortly after the rediscovery of mendelian genetics. That retroviral genomes can oscillate between infectious and genetic modes of transmission seemed preposterous before the discovery of reverse transcription in 1970. Those of us who had earlier provided mendelian evidence for germ-line transmission of retroviruses were subject of friendly ridicule. Today, the shunting of genetic elements between chromosomes and RNA, and the generation of processed pseudogenes, seems commonplace. It is timely, however, to revisit the topic of human endogenous retroviruses-the subject of this article.

Animals↗

Aetiology of Kaposi's sarcoma: current understanding and implications for therapy.

Kaposi's sarcoma is an angiogenic neoplasm composed of endothelial and spindle cells. The enormous increase in Kaposi's sarcoma with HIV infection, and recent discovery that a new human herpesvirus (Kaposi's sarcoma-associated herpesvirus, also called human herpesvirus 8) is present in this tumor, has activated intense interest in the aetiology, epidemiology and pathogenesis of this disease. Today, Kaposi's sarcoma is one of the most frequent neoplasms in men under 50 years old in the USA, and in some African countries it is the most common tumour overall.

AIDS-Related Opportunistic Infections↗