A cell-penetrating helical peptide as a potential HIV-1 inhibitor.

The capsid domain of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein is a critical determinant of virus assembly, and is therefore a potential target for developing drugs for AIDS therapy. Recently, a 12-mer alpha-helical peptide (CAI) was reported to disrupt immature- and mature-like capsid particle assembly in vitro; however, it failed to inhibit HIV-1 in cell culture due to its inability to penetrate cells. The same group reported the X-ray crystal structure of CAI in complex with the C-terminal domain of capsid (C-CA) at a resolution of 1.

Babesia divergens: identification and characterization of BdHSP-20, a small heat shock protein.

This study describes the identification and characterization of the Babesia divergens alpha-crystallin/small heat shock protein 20 (BdHSP-20). BdHSP-20 was recognized by the DG7 monoclonal antibody (DG7 mAb) originally produced by Precigout et al. [Precigout, E.

Combined neonatal blood transplants in a parent-to-F1 mouse model: improved survival rates and stable long-term engraftment.

The use of cord blood (CB) transplantation for adult patients is limited by the relatively low cell content of a single collection. Two, partially-matched CB grafts could provide optimal cell doses. The interactions among the donor-derived populations have not been fully evaluated.

Expression profiles of mouse Kell, XK, and XPLAC mRNA.

Kell and XK are related because in red cells they exist as a disulfide-bonded complex. Kell is an endothelin-3-converting enzyme, and XK is predicted to be a transporter. Absence of XK, which is accompanied by reduced Kell on red cells, results in acanthocytosis and late-onset forms of central nervous system and neuromuscular abnormalities that characterize the McLeod syndrome.

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides.

Background: Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined.

Violence and HIV-related risk among young men who have sex with men.

Limited research has been conducted on threats or violence by family members and sexual partners against young men who have sex with men (MSM). Young MSM, aged 15-22 years, who attended public venues in New York City were enrolled in an anonymous, cross-sectional HIV seroprevalence and risk-behavior study. About two-thirds (68%) of the young MSM reported ever experiencing threats or violence from either family or partners and 25% reported threats or violence by both family and partners.

Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load.

Background: We previously reported successful therapeutic immunization in a chimpanzee having a relatively low viral load, which was immunized with recombinant plasmid hepatitis B surface antigen (HBsAg) DNA and boosted with recombinant HBsAg encoding canarypox virus. In the present study, we attempted to confirm these findings in an animal with a high virus load.

Methods And Results: We tested three immunization strategies successively over a 3-year period.

Evaluation of the performance of 44 assays used in countries with limited resources for the detection of antibodies to hepatitis C virus.

Background: This study was conducted by the International Consortium for Blood Safety (ICBS) and its Collaborating Center, the Paul Ehrlich Institute, to identify high-quality, affordable assays for the detection of hepatitis C virus (HCV) antibodies and make available information on their performance for the benefit of developing countries.

Study Design And Methods: Forty-four assays were evaluated for their sensitivity and specificity. The assays' sensitivity was evaluated on a characterized panel of 200 anti-HCV-positive samples comprising major HCV genotypes 1 through 6.

A single amino acid substitution (R441A) in the receptor-binding domain of SARS coronavirus spike protein disrupts the antigenic structure and binding activity.

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits.

Risk factors for HIV infection among men who have sex with men.

Objectives: Risk factors for HIV acquisition were examined in a recent cohort of men who have sex with men (MSM).

Design: A longitudinal analysis of 4295 HIV-negative MSM enrolled in a randomized behavioral intervention trial conducted in six US cities.

Methods: MSM were enrolled and assessed for HIV infection and risk behaviors semi-annually, up to 48 months.

Endothelin-3-converting enzyme activity of the KEL1 and KEL6 phenotypes of the Kell blood group system.

The Kell blood group protein is a metalloendopeptidase that preferentially cleaves a Trp(21)-Ile(22) bond of big endothelin-3 producing bioactive endothelin-3. Kell is a polymorphic protein, and 25 different phenotypes, because of point mutations resulting in single amino acid substitutions, have been described. It was recently reported that a recombinant form of KEL1 (K, K1) phenotype, expressed in K562 and HEK293 cells, had no endothelin-3-converting activity, in contrast to the common KEL2 (k, K2) phenotype.

Individual donor nucleic acid amplification testing for detection of West Nile virus.

We have developed an economical, high-throughput nucleic acid amplification test (NAT) for blood-borne viruses, suitable for use in the screening of plasma samples from individual blood donors. This assay system includes a semiautomated procedure, using 96-well glass fiber plates for the extraction of viral nucleic acids from plasma and "universal beacon" technology which permits the detection of all genotypes of highly variable viruses (e.g.

Application of 3D-QSAR techniques in anti-HIV-1 drug design--an overview.

Despite the availability of several classes of drugs against acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type 1(HIV-1), this deadly disease showing very little sign of containment, especially in Sub-Saharan Africa and South-East Asia. More than 20 million people died since the first diagnosis of AIDS more than twenty years ago and almost 40 million people are currently living with HIV/AIDS. Structure-based drug design effort was immensely successful in identifying several drugs that are currently available for the treatment of HIV-1.

Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.

We have identified two N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamide analogs as a novel class of human immunodeficiency virus type 1 (HIV-1) entry inhibitors that block the gp120-CD4 interaction, using database screening techniques. The lead compounds, NBD-556 and NBD-557, are small molecule organic compounds with drug-like properties. These compounds showed potent cell fusion and virus-cell fusion inhibitory activity at low micromolar levels.

Onset of expression of the components of the Kell blood group complex.

Background: Kell and XK, two distinct red blood cell membrane proteins, are linked by a disulfide bond and form the Kell blood group complex. Kell surface antigens are expressed early during erythropoiesis but the onset of expression of XK which carries the Kx antigen is unknown.

Study Design And Methods: To determine whether Kell and XK are synchronously expressed, sorted human hematopoietic progenitor cells and mouse progenitor cells of defined lineage were studied.

rOv-ASP-1, a recombinant secreted protein of the helminth Onchocercavolvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens.

We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type.

Theaflavin derivatives in black tea and catechin derivatives in green tea inhibit HIV-1 entry by targeting gp41.

Theaflavin derivatives and catechin derivatives are the major polyphenols in black tea and green tea, respectively. Several tea polyphenols, especially those with galloyl moiety, can inhibit HIV-1 replication with multiple mechanisms of action. Here we showed that the theaflavin derivatives had more potent anti-HIV-1 activity than catechin derivatives.

Altered glycosylation leads to Tr polyagglutination.

Background: Polyagglutination refers to red blood cells (RBCs) that are agglutinated by a high proportion of ABO-matched adult sera but not by cord sera. Polyagglutinable RBCs have been associated with microbial infection, myeloproliferative disorders, and myelodysplasia. Lectins aid in the identification of polyagglutination.

Development of Duffy transgenic mouse: in vivo expression of human Duffy gene with -33T-->C promoter mutation in non-erythroid tissues.

Blood group Duffy gene (FY) promoter in Duffy-negative individuals contains a point mutation in the GATA1 protein-binding motif, which was suggested to be responsible for erythroid suppression of FY. We developed two transgenic mouse lines with FY from both Duffy phenotypes. Transgenic mice with FY from Duffy-positive phenotype expressed Duffy protein both in red blood cells (RBCs) and non-erythroid tissues.

Hepatitis C virus replication kinetics in chimpanzees with self-limited and chronic infections.

The availability of molecular beacon-based, real time polymerase chain reaction (PCR) and a semi-automated sample extraction procedure have made it possible for us to retrospectively examine HCV replication kinetics in HCV naive chimpanzees infected during the past 20 years. We compared these in 17 animals that developed chronic infection, and in 21 that developed self-limited infection. No differences were found in infecting dose, or replication kinetics in the acute phase between these two types of infection.

Murine bone marrow cells cultured ex vivo in the presence of multiple cytokine combinations lose radioprotective and long-term engraftment potential.

The desire to improve engraftment following transplantation of limited numbers of hematopoietic stem cells (HSC) has spurred the investigation of ex vivo stem cell expansion techniques. While surrogate outcomes, such as an increase in SCID-repopulating cells, suggest successful stem cell expansion in some studies, it is not clear that such assays predict outcomes using a more clinically relevant approach (e.g.

Risk factors for coronary artery disease and the use of neural networks to predict the presence or absence of high blood pressure.

Background: The Framingham Heart Study was initiated in 1948 as a long-term longitudinal study to identify risk factors associated with cardiovascular disease (CVD). Over the years the scope of the study has expanded to include offspring and other family members of the original cohort, marker data useful for gene mapping and information on other diseases. As a result, it is a rich resource for many areas of research going beyond the original goals.