Pioneering Point-Of-Care Testing for Integration of Germline and Tumor Genetics in Breast Cancer Risk Management: A Vision for the Future of Translational Pharmacogenomics.

Research performed in South African (SA) breast, ovarian and prostate cancer patients resulted in the development of a rapid BRCA point-of-care (POC) assay designed as a time- and cost-effective alternative to laboratory-based technologies currently used for first-tier germline DNA testing. In this study the performance of the new assay was evaluated for use on a portable screening device (ParaDNA), with the long-term goal to enable rollout at POC as an inventive step to meet the World Health Organization's sustainable development goals for Africa. DNA samples for germline testing were obtained retrospectively from 50 patients with early-stage hormone receptor-positive breast cancer referred for genomic tumor profiling (MammaPrint).

Changes in differential gene expression during a fatal stroke.

We present a young woman (with an identical twin sister) who arrived at the Emergency Department (ED) within 1 hour of her initial stroke symptoms. Previous microarray studies have demonstrated differential expression of multiple genes between stroke patients and healthy controls. However, for many of these studies there is a significant delay between the initial symptoms and collection of blood samples, potentially leaving the important early activators/regulators of the inflammatory response unrecognised.

Changes in differential gene expression during a fatal stroke.

We present a young woman (with an identical twin sister) who arrived at the Emergency Department (ED) within 1hour of her initial stroke symptoms. Previous microarray studies have demonstrated differential expression of multiple genes between stroke patients and healthy controls. However, for many of these studies there is a significant delay between the initial symptoms and collection of blood samples, potentially leaving the important early activators/regulators of the inflammatory response unrecognised.

Genomic responses during acute human anaphylaxis are characterized by upregulation of innate inflammatory gene networks.

Background: Systemic spread of immune activation and mediator release is required for the development of anaphylaxis in humans. We hypothesized that peripheral blood leukocyte (PBL) activation plays a key role.

Objective: To characterize PBL genomic responses during acute anaphylaxis.

Ultrarush versus semirush initiation of insect venom immunotherapy: a randomized controlled trial.

Background: Venom immunotherapy can be initiated by different schedules, but randomized comparisons have not been performed.

Objective: We aimed to compare the safety of 2 initiation schedules.

Methods: Patients of any age with prior immediate generalized reactions to jack jumper ant (Myrmecia pilosula) stings were randomized to venom immunotherapy initiation by a semirush schedule over 10 visits (9 weeks) or an ultrarush schedule over 3 visits (2 weeks).

Causes of ant sting anaphylaxis in Australia: the Australian Ant Venom Allergy Study.

Objective: To determine the Australian native ant species associated with ant sting anaphylaxis, geographical distribution of allergic reactions, and feasibility of diagnostic venom-specific IgE (sIgE) testing.

Design, Setting And Participants: Descriptive clinical, entomological and immunological study of Australians with a history of ant sting anaphylaxis, recruited in 2006-2007 through media exposure and referrals from allergy practices and emergency physicians nationwide. We interviewed participants, collected entomological specimens, prepared reference venom extracts, and conducted serum sIgE testing against ant venom panels relevant to the species found in each geographical region.

Using time-resolved fluorescence to measure serum venom-specific IgE and IgG.

We adapted DELFIA™ (dissociation-enhanced lanthanide fluoroimmunoassay), a time resolved fluorescence method, to quantitate whole venom specific and allergenic peptide-specific IgE (sIgE), sIgG(1) and sIgG(4) in serum from people clinically allergic to Australian native ant venoms, of which the predominant cause of allergy is jack jumper ant venom (JJAV). Intra-assay CV was 6.3% and inter-assay CV was 13.

Early vascular and neuronal changes in a VEGF transgenic mouse model of retinal neovascularization.

Purpose: To investigate early retinal changes in a vascular endothelial growth factor (VEGF) transgenic mouse (tr029VEGF; rhodopsin promoter) with long-term damage that mimics nonproliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (PDR).

Methods: Rhodopsin and VEGF expression was assessed up to postnatal day (P)28. Vascular and retinal changes were charted at P7 and P28 using sections and wholemounts stained with hematoxylin and eosin or isolectin IB4 Griffonia simplicifolia Samples were examined using light, fluorescence, and confocal microscopy.

Timed ablation of regulatory CD4+ T cells can prevent murine AIDS progression.

We describe successful immunotherapy of murine AIDS (MAIDS) in C57BL/6J mice based on the elimination of replicating CD4(+) regulator T cells. We demonstrate that a single injection of the antimitotic drug vinblastine (Vb) given 14 days postinfection (p.i.

Co-operative learning processes of students: a longitudinal multilevel perspective.

Background: This article describes the outcomes of a longitudinal, multilevel observational study in which the relationship between the processes of co-operation and giving explanations was compared between classes trained in communication skills and classes that were untrained.

Aims: This study examined the effects of training in basic communication skills on the processes of co-operation and giving explanation in co-operative groups. In particular, the study investigated: (a) How the processes of co-operation and giving explanations develop over time; (b) How the underlying processes of co-operation and giving explanations are related; (c) Which factors at the student and class level facilitate or hinder these processes.

Religion as a cross-cultural determinant of depression in elderly Europeans: results from the EURODEP collaboration.

Background: The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans.

Methods: Two approaches were employed, using data from the EURODEP collaboration.

Endothelin receptor antagonism ameliorates mast cell infiltration, vascular hypertrophy, and epidermal growth factor expression in experimental diabetes.

Vascular hypertrophy, a feature of experimental and human diabetes, has been implicated in the pathogenesis of the microvascular and macrovascular complications of the disease. In the present study, we sought to examine the role of endogenous endothelin and its relation to vascular growth factors in the mediation of vascular hypertrophy in experimental diabetes and to examine the contribution of mast cells to this process. Vessel morphology, endothelin, growth factor gene expression, and matrix deposition were studied in the mesenteric arteries of control and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without the dual endothelin(A/B) receptor antagonist bosentan (100 mg x kg(-1) x d(-1)) during a 3-week period.

Religious climate and geographical distribution of depressive symptoms in older Dutch citizens.

This study examines whether the degree of conservatism of the religious climate affects the geographical distribution of late life depressive symptoms. A U-shaped relationship is hypothesized: high levels of depressive symptoms at the extremes (both a-religious and hyperconservative), and a low level in the middle (moderate-conservative). Subjects are 3051 older Dutch citizens (55-85 years), living in 11 municipalities.

Religious denomination and depression in older Dutch citizens: patterns and models.

This study describes the distribution of depressive symptoms in older Dutch citizens (N = 3,020) across religious denominations. Reformed Calvinists had the lowest depressive scores (CES-D); Protestants from liberal denominations the highest; Roman Catholics, Dutch Reformed, and nonchurch members were in between. Two types of explanatory mechanisms are examined: (a) social integration and (b) positive self-perceptions, which both help to prevent depression.

Regulation of c-Myb through protein phosphorylation and leucine zipper interactions.

c-Myb function is modulated in part by a negative regulation domain which encompasses a leucine zipper (LZ). When E. coli-expressed c-Myb with wild type or mutated LZ proteins are assessed for DNA binding activity, the mutant form is substantially better at DNA binding than the wild type (WT) form.

A cell line (LIM 2463) derived from a tubulovillous adenoma of the rectum.

We describe a new epithelial cell line (LIM 2463) derived from tubulovillous adenoma of the rectum. The cells grow as organoids and secrete large amounts of mucus. The cells are polarized, with a microvillar brush border, and express dipeptidyl peptidase IV in a polarized manner.

Lack of an association between carcinoma of the stomach and the major histocompatibility complex (HLA) in Cape Coloureds.

A possible genetic contribution to the high incidence of gastric carcinoma in the Cape Coloured population of the Western Cape region of South Africa was investigated. The HLA-A, B, C, DR and DQ antigens were determined with a microcytotoxicity assay, and their frequencies compared in 124 individuals with gastric carcinoma and 4,560 controls. No significant difference was found, thus supporting the view that a genetic component has a minor, if any, role in gastric carcinogenesis.

Gastric juice carcino-embryonic antigen estimation. A useful additional test in the diagnosis of gastric carcinoma?

There is a high incidence of gastric carcinoma in the coloured population of the Western Cape. Diagnostic tests other than barium meal examination or gastroscopy were investigated. In this study 50 patients were assessed and grouped according to the gastroscopic and histological findings.

Gastric carcinoma at Tygerberg Hospital, 1979-1983. A retrospective study.

A retrospective study was carried out on patients with histologically proven gastric carcinoma diagnosed at the Gastro-intestinal Clinic, Tygerberg Hospital, over a 5-year period--1979-1983. Fifty per cent of patients were coloured men. The overall median age was 65 years but the coloured patients were significantly younger than the white.

A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part I. Clinical features.

Crimean-Congo haemorrhagic fever (CCHF) is a rare disease in South Africa. From 1981 to September 1984, 8 sporadic primary cases were reported. An outbreak of CCHF in a large university hospital is described; of 8 patients diagnosed 2 died (the index and a secondary case).

A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part IV. Preventive and prophylactic measures.

During the Crimean-Congo haemorrhagic fever (CCHF) outbreak at Tygerberg Hospital a particular problem existed: a simultaneous influenza epidemic complicated the screening of contacts because of its very similar clinical picture to that of early CCHF. The methods of identifying and screening contacts are described. Of 459 listed CCHF contacts, 7 (1,5%) developed the disease; 6 were contacts of the index case and only 1 a contact of a secondary case.