Measurement of mitochondrial DNA copy number in dried blood spots: A pilot study.

Background: We evaluated the feasibility of mitochondrial DNA (mtDNA) copy number measurement in dried blood spots (DBS), its comparability with measurement in whole blood samples, and stability of mtDNA copy number from DBS over time.

Methods: Women in this pilot study were participants in the Sister Study, a large prospective cohort. Sister Study participants provided a whole blood sample and DBS at enrollment.

Sox2 controls Schwann cell self-organization through fibronectin fibrillogenesis.

The extracellular matrix is known to modulate cell adhesion and migration during tissue regeneration. However, the molecular mechanisms that fine-tune cells to extra-cellular matrix dynamics during regeneration of the peripheral nervous system remain poorly understood. Using the RSC96 Schwann cell line, we show that Sox2 directly controls fibronectin fibrillogenesis in Schwann cells in culture, to provide a highly oriented fibronectin matrix, which supports their organization and directional migration.

The Sister Study Cohort: Baseline Methods and Participant Characteristics.

Background: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures.

Objective: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer.

Methods: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors.

Perfusion Controlled Mobilization after Lower Extremity Free Flaps-Pushing the Limits of Time and Intensity.

 The current standard to gradually adapt the fragile perfusion in lower extremity free flaps to an upright posture is the dangling maneuver. This type of flap training neither fits the orthostatic target load of an upright posture, nor does it assist in mobilizing the patients effectively. In this study, we quantitatively analyzed training effects of an early and full mobilization on flap perfusion.

Less Is More? Impact of Single Venous Anastomosis on the Intrinsic Transit Time of Free Flaps.

 The number of venous anastomoses advisable for a free flap continues to be controversial. Intrinsic transit time (ITT) is the time it takes dye during indocyanine green (ICG) microangiography to travel from the arterial to the venous anastomosis. ITT provides information on blood flow velocity and can predict postoperative circulatory complications.

Arteriovenous Loop-Independent Free Flap Reconstruction of Sternal Defects after Cardiac Surgery.

Background Sternal defects following deep wound infections are predominantly reconstructed using local and regional flaps. The lack of appropriate recipient vessels after cardiac surgery may explain the minor role of free flaps. To date, arteriovenous loops have been the leading solution to enable microsurgical closure of these defects.

Standard preanalytical coding for biospecimens: defining the sample PREanalytical code.

Background: Management and traceability of biospecimen preanalytical variations are necessary to provide effective and efficient interconnectivity and interoperability between Biobanks.

Methods: Therefore, the International Society for Biological and Environmental Repositories Biospecimen Science Working Group developed a "Standard PREanalytical Code" (SPREC) that identifies the main preanalytical factors of clinical fluid and solid biospecimens and their simple derivatives.

Results: The SPREC is easy to implement and can be integrated into Biobank quality management systems and databases.

Changes in adherence to highly active antiretroviral therapy medications in the Multicenter AIDS Cohort Study.

Objectives: To characterize the determinants of changes in adherence to antiretroviral therapy and examine whether there are persistent lower adherers.

Design: A cohort study with repeated measurements.

Methods: Self-reported 100% adherence was defined as taking all doses and numbers of pills over a 4-day period as prescribed for current HIV medications.

CC chemokine receptor 5 genotype and susceptibility to transmission of human immunodeficiency virus type 1 in women.

The human gene for CC chemokine receptor 5, a coreceptor for human immunodeficiency virus type 1 (HIV-1), affects susceptibility to infection. Most studies of predominantly male cohorts found that individuals carrying a homozygous deleted form of the gene, Delta 32, were protected against transmission, but protection did not extend to Delta 32 heterozygotes. The role played by this mutation in HIV-1 transmission to women was studied in 2605 participants in the Women's Interagency HIV Study.

High levels of antibodies to the CD4 binding domain of human immunodeficiency virus type 1 glycoprotein 120 are associated with faster disease progression.

Human monoclonal antibodies (Abs) to the CD4 binding domain of human immunodeficiency virus (HIV) type 1 glycoprotein (gp) 120 (gp120(CD4bd)) inhibit gp120 presentation to gp120-specific T helper (Th) cells. Since Th responses are critical to control HIV, anti-gp120(CD4bd) Abs could be involved in HIV pathogenesis. Therefore, anti-gp120(CD4bd) Ab levels were compared in serum samples from matched pairs of HIV-positive rapid progressors (RPs) and slow progressors (SPs).

Determinants of heterogeneous adherence to HIV-antiretroviral therapies in the Multicenter AIDS Cohort Study.

Assessment of adherence to HIV antiretroviral therapy (ART) is required for studying therapeutic effectiveness and identifying subgroups needing focused education. The study's goals were to describe the level of ART adherence using self-reported recall over a 4-day period and to characterize determinants of lower adherence. The interaction between adherence and drug holidays on level of HIV RNA also was investigated.

HIV-associated neurologic disease incidence changes:: Multicenter AIDS Cohort Study, 1990-1998.

This study examined the temporal trends in the incidence rates of HIV dementia, cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy, and CNS lymphoma from January 1990 to December 1998 in the Multicenter AIDS Cohort Study. The incidence rates for HIV dementia, cryptococcal meningitis, and lymphoma decreased following the introduction of highly active antiretroviral therapy (HAART). The proportion of new cases of HIV dementia with a CD4 count in a higher range (i.

Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study.

Objective: To examine whether polymorphism in the RANTES gene is associated with HIV disease outcome.

Design: RANTES, a ligand of the major HIV co-receptor, CCR5, is known to block HIV-CCR5 interactions. Recently, two single nucleotide polymorphisms in the RANTES gene promoter region, designated -403G/A and -28C/G, have been described.

A longitudinal study of neutralizing antibodies and disease progression in HIV-1-infected subjects.

Sera from human immunodeficiency virus-1-infected participants in the Multicenter AIDS Cohort Study were tested to assess the association between serum neutralizing antibodies (NAbs) and disease progression. Each of 14 pairs, retrospectively matched for age, sex, race, and CD4+ lymphocyte numbers early in the study, consisted of a rapid progressor (RP) who developed AIDS and a long-term nonprogressor (LTNP) who remained asymptomatic. Serum samples were drawn early, when all participants were asymptomatic, and late, when the RPs had developed clinical AIDS.

Viability and recovery of peripheral blood mononuclear cells cryopreserved for up to 12 years in a multicenter study.

The Multicenter AIDS Cohort Study (MACS), an ongoing prospective study of the natural history of human immunodeficiency virus (HIV), has stored biologic specimens, including peripheral blood mononuclear cells (PBMC), from 5,622 participants for up to 12 years. The purpose of the present analysis was to evaluate the quality of the PBMC in the MACS repository in order to test the validity and feasibility of nested retrospective studies and to guide the planning of future repositories. PBMC were collected from MACS participants at four centers at 6-month intervals from 1984 to 1995, cryopreserved, and transported to a central repository for storage.

CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS).

Background: The rate of progression to AIDS varies among individuals infected with HIV-1. Factors responsible include two inherited human alleles, CCR5 delta32 and CCR2-641, which alter the protein-coding regions for the HIV-1 coreceptors/chemokine receptors CCR5 and CCR2b. We tested the hypothesis that polymorphisms of the CCR5 promoter might affect the rate of progression of HIV-1 infected people to AIDS.

Virologic and serologic markers of rapid progression to AIDS after HIV-1 seroconversion.

The association between early virologic and immunologic events after human immunodeficiency virus type 1 (HIV-1) infection and progression of HIV-1 infection to acquired immunodeficiency syndrome (AIDS) was studied among 59 homosexual men with documented time of seroconversion. Epidemiologic factors, such as number of lifetime sexual partners, history of sexually transmitted diseases, and other factors, also were studied. All 17 seroconverters in the cohort who developed AIDS within 3 years (rapid progressors = RPs) were compared with 42 men without AIDS for at least 6 years seroconversion (nonrapid progressors = non-RPs).

Psychomotor slowing in HIV infection: a predictor of dementia, AIDS and death.

The objective of this study was to determine if sustained decline in psychomotor speed tests is associated with an increased risk of progression to dementia, acquired immunodeficiency syndrome (AIDS), or mortality in human immunodeficiency virus (HIV)-1-infected homosexual men in the Baltimore site of the Multicenter AIDS Cohort-Study (MACS). Clinical and neuropsychological data were obtained on 291 HIV+ homosexual men seen semi-annually over a nine year period (1986-1994). A proportional hazards model was used to assess the predictive value of sustained psychomotor slowing (defined as a 2.

HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates with rate of disease progression.

The Ab-dependent cell-mediated cytotoxicity (ADCC) activity of anti-gp120 Abs in serum from four groups of HIV-1-positive individuals in the Multicenter AIDS Cohort Study was evaluated at several time points over a 10-yr period. HIV-1-positive individuals who progressed to AIDS within 3 yr of seroconversion (rapid progressors) were compared with seroconverters who did not progress to AIDS within 6 yr (nonrapid progressors) and individuals who were seropositive when they entered the study and did not progress to AIDS within 9-10 yr (nonprogressors). At the visit closest to AIDS, rapid progressors had significantly lower titers of Abs that mediate ADCC against HIV-1 gp120 than those of nonrapid progressors at corresponding visits or those of nonprogressors at any visit.