Biomedical subjects

Andrew Blauvelt

Publications and source records attributed to Andrew Blauvelt.

26 records · Page 2Linked to original sources

PubMed2003

Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C.

Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4(+) T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pol genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression.

Cells, Cultured↗

PubMed2002

Stromal-derived factor 1 expression in the human thymus.

Stromal-derived factor-1 (SDF-1), the only known ligand for the chemokine receptor CXCR4, is broadly expressed in cells of both the immune and central nervous systems, and it can induce the migration of resting leukocytes and hemopoietic progenitors. SDF-1 mRNA was previously detected in human thymus-derived stromal cells, but its role in thymopoiesis was unknown. Here we show that SDF-1 is expressed in medullar epithelial cells forming Hassall's corpuscles (HC). In search of the cell type that may be attracted by SDF-1(+) cells in the medulla, we determined that dendritic cells (DC) could be found in situ in close proximity to SDF-1(+) epithelial cells in HC. In HIV-1-infected SCID-hu thymuses, DC contained apoptotic cells and were located within enlarged HC. It was further demonstrated that uptake of apoptotic thymocytes by immature DC induced an increase in CXCR4 expression and SDF-1-mediated chemotaxis. Our data suggest a role for SDF-1 in the elimination of apoptotic thymocytes.

Animals↗

PubMed2002

Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10.

BACKGROUND: In several open-label studies, recombinant human interleukin 10 (rhIL-10), a type 2 anti-inflammatory cytokine, has been reported to improve psoriasis, a disease characterized by type 1 cytokine inflammation. OBJECTIVE: To evaluate the safety, efficacy, and immunologic parameters in individuals with psoriasis treated with rhIL-10. DESIGN AND INTERVENTION: Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner. SETTING AND PATIENTS: National Institutes of Health Clinical Center in Bethesda. Twenty-eight patients with moderate-to-severe psoriasis as defined by a Psoriasis Area Severity Index (PASI) score of 10 or higher. MAIN OUTCOME MEASURE: The primary clinical end point was the mean percentage change in the PASI score comparing baseline and week 12 scores. Intracellular cytokine production by peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry. RESULTS: There was no significant difference in the mean percentage change in the PASI score from baseline to week 12 between the rhIL-10-treated group and control patients (17% vs 13% improvement, respectively; P =.69), although a modest trend toward improvement in patients receiving rhIL-10 was documented at both the 6- and 8-week points. Interestingly, proinflammatory and type 1 cytokine production by PBMCs progressively declined in the rhIL-10-treated patients during the entire 12-week study period. CONCLUSIONS: Treatment with rhIL-10 resulted in only temporary clinical improvement in psoriasis, despite sustained systemic decreases in proinflammatory and type 1 cytokine production. These data suggest that immunotherapy that decreases the ratio of systemic type 1 and type 2 cytokine production does not necessarily lead to improvement of type 1 cytokine-mediated disease.

Adult↗

PubMed2002

Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines.

Corticosteroid use in transplant recipients increases the incidence and severity of Kaposi's sarcoma (KS), a disease associated with KS-associated herpesvirus (KSHV) infection. Recently, the prototypic corticosteroid, hydrocortisone, was shown to directly induce lytic cycle reactivation of KSHV in latently-infected BCBL-1 cells. The purpose of this study was to examine this phenomenon in further detail. After incubation with dexamethasone (<or= 30 microM) or hydrocortisone (<or= 30 microM) for 1-4 days, we evaluated KSHV reactivation in latently infected B cell lines (BC-1, BC-3, and BCBL-1) by assessing early-lytic PF-8 and late-lytic gpK8.1 protein expression using flow cytometry. Viral particle production was monitored by quantifying KSHV minor capsid protein levels in cell culture supernatants. A small increase in the percentage of cells expressing viral lytic proteins was observed in BCBL-1, but not in the other cell lines. In combination with 3 nM 12-O-tetradecanoyl-phorbol-13-acetate, a known chemical inducer of KSHV replication, corticosteroids (0.3 microM) enhanced KSHV reactivation twofold in some cell lines, but not in others. In all experiments, lytic viral protein expression by flow cytometry correlated with production of viral particles in culture supernatants. In summary, we found that corticosteroids were limited inducers of KSHV reactivation in latently infected cells. Thus, our findings suggest that corticosteroids do not enhance the incidence and severity of KS in transplant recipients by direct cellular effects on KSHV reactivation.

Adrenal Cortex Hormones↗

PubMed2002

Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

Pityriasis rosea is a common skin disease that has been suspected to have a viral etiology. We performed nested polymerase chain reaction to detect human herpesvirus-7, human herpesvirus-6, and cytomegalovirus DNA in lesional skin, nonlesional skin, peripheral blood mononuclear cells, serum, and saliva samples isolated from 14 pityriasis rosea patients. Viral mRNA expression and virion visualization within lesional skin were studied by in situ hybridization and transmission electron microscopy, respectively. By nested polymerase chain reaction, human herpesvirus-7 DNA was present in lesional skin (93%), nonlesional skin (86%), saliva (100%), peripheral blood mononuclear cells (83%), and serum (100%) samples, whereas human herpesvirus-6 DNA was detected in lesional skin (86%), nonlesional skin (79%), saliva (80%), peripheral blood mononuclear cells (83%), and serum (88%) samples. By contrast, cytomegalovirus DNA was not detected in these tissues. Control samples from 12 healthy volunteers and 10 psoriasis patients demonstrated rare positivity for either human herpesvirus-7 or human herpesvirus-6 DNA in skin or serum. By in situ hybridization, infiltrating mononuclear cells expressing human herpesvirus-7 and human herpesvirus-6 mRNA were identified in perivascular and periappendageal areas in 100% and 75% pityriasis rosea skin lesions, respectively, compared to herpesviral mRNA positivity in only 13% normal skin and psoriasis skin controls. Transmission electron microscopy failed to reveal herpesviral virions in pityriasis rosea lesional skin. Nested polymerase chain reaction and in situ hybridization enabled detection of human herpesvirus-7 and human herpesvirus-6 in skin and other tissues isolated from patients with pityriasis rosea. These results suggest that pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

Adolescent↗

PubMed2002

Essential roles for dendritic cells in the pathogenesis and potential treatment of HIV disease.

During sexual transmission of HIV, virus crosses mucosal epithelium and eventually reaches lymphoid tissue where it establishes a permanent infection. Evidence has accumulated that infection of Langerhans cells, which are resident dendritic cells in pluristratified epithelia, plays a crucial role in the early events of HIV transmission. HIV infection of Langerhans cells is regulated by surface expression of CD4 and CCR5. Thus, topical microbicides that interfere with HIV infection of Langerhans cells represent an attractive strategy for blocking sexual transmission of virus. Capture and uptake of HIV virions is another major pathway by which HIV interacts with dendritic cells. By contrast, this process is mediated by a newly described C-type lectin, DC-SIGN. It is well established that HIV-exposed dendritic cells transmit virus efficiently to cocultured T cells. Indeed, dendritic cell-T cell interaction, critical in the generation of immune responses, is a rich microenvironment for HIV replication both in vitro and in vivo. Dendritic cells that have captured virus via DC-SIGN, and not HIV-infected dendritic cells, probably facilitate most infection of T cells in chronically infected individuals. Therefore, blocking DC-SIGN-mediated capture of HIV represents a potential therapeutic antiviral strategy for HIV disease. Lastly, dendritic cells have been targeted both ex vivo and in vivo to initiate and enhance HIV-specific immunity. Although these approaches are promising for both therapeutic and prophylactic vaccines, much additional work is needed in order to optimize dendritic-cell-based immunization strategies.

AIDS Vaccines↗

PubMed2002

Quantifying the harmful effect of psoriasis on health-related quality of life.

BACKGROUND: Psoriasis affects 7 million people in the United States, causing substantial cost, social stigma, and disability. OBJECTIVE: The purpose of this study was to evaluate the health effects of skin disease by comparing psoriasis to other primary medical disorders using 3 different scales of health-related quality of life. METHODS: A self-administered questionnaire consisting of 3 health-related quality of life measures was given sequentially to 35 eligible patients with psoriasis presenting to the Dermatology Branch of the National Cancer Institute (NCI) for an investigational therapeutic protocol. RESULTS: All patients (100%) agreed to participate. The median Psoriasis Area and Severity Index (PASI) score was 13.0. Overall, 82.9% at least often felt the need to hide their psoriasis, and 74.3% claimed their self-confidence was at least often affected by their psoriasis. The median EQ-5D health state utility score was 13.0% less than healthy individuals (P <.001). On the SF-36, the mean general health score was 13.2% less (P =.005) and the median social functioning score 18.7% less (P =.005) than that of patients with no chronic conditions. CONCLUSION: Individuals with psoriasis are significantly affected in their health state utility, perception of general health, and social functioning when compared with individuals without chronic disease and those with certain primary medical conditions.

Female↗

PubMed2002

The future of academic dermatology in the United States: report on the resident retreat for future physician-scientists, June 15-17, 2001.

Fewer and fewer residents appear to be choosing careers in academic dermatology and research. Recognizing the impact that this trend would have on the future of our specialty, the Society for Investigative Dermatology invited a group of dermatology residents and academic dermatologists to participate in a retreat whose aim was to identify the reasons behind this trend and to begin to address these issues.

Adult↗