Prevalence of PALB2 mutations in Australasian multiple-case breast cancer families.

Introduction: Population-based studies of breast cancer have estimated that some PALB2 mutations confer a breast cancer risk (penetrance) comparable to the average pathogenic mutation in BRCA2. As this risk is of clinical relevance, we sought to identify mono-allelic PALB2 mutations and determine their frequencies in multiple-case breast cancer families attending Familial Cancer Clinics in Australia and New Zealand.

Methods: The youngest affected woman, not known to carry a mutation in BRCA1 or BRCA2, from 747 multiple-case breast cancer families participating in kConFab were selected for PALB2 mutation screening.

Viral phenotypes and antibody responses in long-term survivors infected with attenuated human immunodeficiency virus type 1 containing deletions in the nef and long terminal repeat regions.

The Sydney Blood Bank Cohort (SBBC) consists of eight blood transfusion recipients infected with nef-attenuated human immunodeficiency virus type 1 (HIV-1) acquired from a single donor. Here, we show that viral phenotypes and antibody responses differ considerably between individual cohort members, despite the single source of infection. Replication of isolated virus varied from barely detectable to similar to that of the wild-type virus, and virus isolated from five SBBC members showed coreceptor usage signatures unique to each individual.

Broad neutralization and complement-mediated lysis of HIV-1 by PEHRG214, a novel caprine anti-HIV-1 polyclonal antibody.

Objectives: To assess the potency, breadth of action, and mechanism of action of the polyclonal goat anti-HIV antibody, PEHRG214.

Design: Typical human antibody responses to HIV-1 infection are unable to neutralize virus efficiently, clear the infection, or prevent disease progression. However, more potent neutralizing antibodies may be capable of playing a pivotal role in controlling HIV replication in vivo.

Longitudinal analysis of nef/long terminal repeat-deleted HIV-1 in blood and cerebrospinal fluid of a long-term survivor who developed HIV-associated dementia.

We studied the evolution and compartmentalization of nef/long terminal repeat (nef/LTR)-deleted human immunodeficiency virus type 1 (HIV-1) from a long-term survivor who developed HIV-associated dementia (HIVD). Analysis of sequential blood-derived HIV-1 isolated before and during HIVD revealed a persistent R5X4 phenotype and a progressive loss of nef/LTR sequence; in contrast, HIV-1 present in cerebrospinal fluid during HIVD had an R5 phenotype, distinct nef/LTR sequence of unique deletions and additional nuclear factor- kappa B sites and specificity factor-1 sites, and enhanced transcriptional activity, compared with the blood-derived isolates. Thus, nef/LTR-deleted HIV-1 strains may undergo compartmentalized evolution in long-term survivors and cause neurologic disease.