- T-cell and Retrovirus Studies
- HIV/AIDS drug development and treatment
- Viral-associated cancers and disorders
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- HIV Research and Treatment
- Renal Transplantation Outcomes and Treatments
- Immune Cell Function and Interaction
- HIV-related health complications and treatments
- Cervical Cancer and HPV Research
- CNS Lymphoma Diagnosis and Treatment
- Tuberculosis Research and Epidemiology
- Colorectal and Anal Carcinomas
- Histiocytic Disorders and Treatments
- HIV/AIDS Research and Interventions
- Molecular Biology Techniques and Applications
- Cytomegalovirus and herpesvirus research
- NF-κB Signaling Pathways
- Bone and Joint Diseases
- RNA Research and Splicing
- Signaling Pathways in Disease
- Multiple Myeloma Research and Treatments
- Nuclear Structure and Function
University of California San Diego Medical Center
2024
University of California, San Diego
2010-2023
VA San Diego Healthcare System
2007-2023
University of California, Los Angeles
1984-2017
University of Arkansas for Medical Sciences
2017
Montefiore Medical Center
2017
University of California, San Francisco
2017
Albert Einstein College of Medicine
2017
Ludwig Cancer Research
2004
Sidney Kimmel Cancer Center
2004
We report a 68-year-old man who received an IV inoculation of WBCs for indium radionuclide scan containing 600 to 700 tissue culture infectious doses human immunodeficiency virus type 1 (HIV-1) from HIV-1-infected individual. The recipient immediately zidovudine, then was switched dideoxyinosine and interferon-alpha, but died hepatorenal syndrome hepatic encephalopathy 15 days later. HIV-1 cultures were positive the recipient's blood on day 14 not 0, 1, 8. At autopsy, parietal lobe isolated...
THE human T-cell lymphotropic viruses Type I (HTLV-I) and II (HTLV-II) the bovine leukemia virus, which are members of a family leukemogenic mammalian retroviruses, share some same structural functional characteristics. HTLV-I has been implicated as causative agent adult leukemia, lymphoid malignant disease endemic to southern Japan Caribbean area.1 2 3 4 5 6 7 8 Bovine virus recognized cause specific diseases cattle.9 10 11 The role HTLV-II in cancer is unclear. This retrovirus with nucleic...
This study examines the contribution of transforming growth factor beta (TGF beta), one most potent endogenous immunosuppressive factors, to development immunodeficiency in human virus (HIV) infection. Increased titers TGF were found supernatants peripheral blood mononuclear cells (PBMCs) from HIV-infected donors as compared uninfected controls (P less than 0.001). correlated closely with defective responses CD4+ lymphocytes recall antigens tuberculin purified protein derivative or tetanus...
Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling limited because spatial information nontumor cell types lost in sample preparation. We scored 88 prostate specimens for relative content tumor, benign hyperplastic epithelium, stroma, dilated cystic glands. The proportions these were then linked silico to levels determined microarray analysis, revealing unique...
The human T-cell leukemia viruses (HTLV) are associated with malignancies in man and will transform normal T cells vitro. mechanism of malignant transformation by HTLV is unknown but appears to be distinct from that other classes retroviruses, which induce through viral or cellular oncogenes. Recently a new gene, termed x , was identified HTLV. This gene has been hypothesized the transforming because its conservation within class retroviruses. By vitro mutagenesis HTLV-II it now demonstrated...
Early detection and treatment of melanoma is important for optimal clinical outcome, leading to biopsy pigmented lesions deemed suspicious the disease. The vast majority such are benign. Thus, a more objective accurate means needed identify excision.To provide proof-of-principle that epidermal genetic information retrieval (EGIR™; DermTech International, La Jolla, CA, U.S.A.), method noninvasively samples cells from stratum corneum by adhesive tape stripping, can be used discern melanomas...
Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Myeloma Research Foundation's Relating Clinical Outcomes in Personal Assessment Genetic Profile study ( NCT01454297 ) longitudinal, observational clinical newly diagnosed patients with multiple (n = 1,143) where samples using whole-genome sequencing, whole-exome sequencing...
Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances effect radiation therapy virus–associated oropharyngeal SCC, we hypothesized that adding to CRT would reduce LRF SCCAC. Methods Forty-five patients stage I III SCCAC infection received CRT: 45 54 Gy primary tumor regional lymph...
Efficient expression of human T-cell leukemia virus type I (HTLV-I) genes requires both host and viral proteins is dependent on DNA sequences in the proviral long terminal repeats (LTRs). We have used DNase I-protection assays (footprinting) to construct a map protein-DNA interactions over 250-nucleotide region LTR upstream start site for RNA synthesis. find that factor (host 1, or HEF-1) binds imperfect 21-nucleotide previously been implicated HTLV-I gene expression. HEF-1 binding activity...
Abstract IL-6 is an important regulator of humoral and cellular immunity. Although this cytokine produced by diverse cell types, it not known whether T lymphocytes under physiologic conditions or which agents can induce expression IL-6. We analyzed the production human peripheral blood cells, thymocytes, lines. In pure populations these stimulated with different combinations various mitogens cytokines, activity could be detected. Analysis purified T-alpha beta T-gamma delta cells showed that...
Intensive chemotherapy for human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) and Hodgkin (HL) has resulted in durable remissions a substantial proportion of patients. High-dose autologous stem cell transplantation (AuSCT), moreover, sustained complete selected patients with recurrent chemosensitive disease. Based on favorable experience dose-reduced high-dose busulfan, cyclophosphamide, AuSCT older non-HIV–associated aggressive lymphomas, an AIDS Malignancy Consortium...
We reported previously that PBMC from HIV+ patients spontaneously release increased levels of TGF beta 1, contributing to defects in cellular immune responses. This study defines the implications overexpression for humoral immunity HIV infection. found upon Staphylococcus aureus Cowan I (SAC) stimulation cells donors, B-lymphocyte proliferative responses were decreased. deficiency correlated closely (r = 0.7, P less than 0.001) with secretion by HIV-infected donors. Conditioned medium and...
Human T-cell leukemia viruses (HTLV) are closely associated with some human leukemias and lymphomas. A unique 3′ region of the HTLV genome is believed to be involved in HTLV-induced cellular transformation, although function this has yet determined. subgenomic messenger RNA transcribed from now been characterized. These results provide direct evidence for expression a novel gene HTLV.
T-cell activation induces expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating (GM-CSF). To define molecular events involved in induction GM-CSF gene more clearly, we prepared and analyzed deletion mutants promoter recombinant constructs. The results localized inducible to a 90-base-pair region (-53 +37) which is active uninfected human leukemia virus-infected lines but not resting or mitogen-stimulated B cells. DNase I footprinting experiments revealed...
The human T-cell leukemia virus (HTLV) types I and II have two nonstructural genes that are encoded in overlapping reading frames. One of these genes, known as tax, has been shown to encode a protein responsible for enhanced transcription (transactivation) from the viral long terminal repeats (LTRs). Genetic evidence indicates second gene HTLV-II, here designated rex, acts trans modulate tax gene-mediated transactivation concentration-dependent fashion. rex may regulate process during life cycle.
A 49-year-old South African man developed a rapidly progressive myelopathy 14 months after blood transfusion and died 1 year the onset of symptoms. Detailed pathologic examination spinal cord was consistent with diagnosis HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although no HTLV-I viral particles, antigens, or nucleic acids were detected in situ, polymerase chain reaction assays revealed proviral DNA cervical, thoracic, lumbar levels cord, greatest amount being at...
The human T-cell leukemia viruses (HTLV) are replication-competent retroviruses whose genomes contain gag, pol, and env genes as well a fourth gene, termed x, which is believed to be the transforming gene of HTLV. product x now shown encoded by 2.1-kilobase messenger RNA derived splicing at least two introns. By means S1 nuclease mapping this nucleic acid sequence analysis complementary DNA clone, complete primary structure x-gene has been determined. It sequences containing initiation codon...