Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis

OBJECTIVE—To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients.
METHODS—27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its *0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and used for DNA oligotyping and sequencing by standard methods.
RESULTS—FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype.
CONCLUSIONS—FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.

     

Tropical enteropathy in Rhodesia.

Tropical enteropathy, which may be related to tropical sprue, has been described in many developing countries including parts of Africa. The jejunal changes of enteropathy are seen in Rhodesians of all social and racial categories. Xylose excretion, however, is related to socioeconomic status, but not race. Upper socioeconomic Africans and Europeans excrete significantly more xylose than lower socioeconomic Africans. Vitamin B12 and fat absorption are normal, suggesting predominant involvement of the proximal small intestine. Tropical enteropathy in Rhodesia is similar to that seen in Nigeria but is associated with less malabsorption than is found in the Caribbean, the Indian subcontinent, and South East Asia. The possible aetiological factors are discussed. It is postulated that the lighter exposure of upper class Africans and Europeans to repeated gastrointestinal infections may accound for their superior xylose absorption compared with Africans of low socioeconomic circumstances. It is further suggested that the milder enteropathy seen in Africa may be explained by a lower prevalence of acute gastroenteritis than in experienced elsewhere in the tropics.     

Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl₃) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl₃ as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD.     

‘Must try harder?’: A family empowerment intervention for acquired brain injury

This paper describes an intervention aimed at empowering parents of child survivors of acquired brain injury (ABI) in their interaction with teachers and other professionals involved in their child's education. The particular characteristics of the late morbidity of child ABI led to the design of an intervention in the form of a video and informational booklet that is the property of the family. Early response to the intervention has been extremely positive, although formal evaluation has been unexpectedly challenging.     

The evolving role of the personal support worker in home care in Ontario,Canada

To meet increasing demand for home care, the role of personal support workers (PSWs) is shifting from providing primarily personal and supportive care to include care activities previously provided by regulated health professionals (RHPs). Much of the research examining this shift focuses on specialty programmes, with few studies investigating the daily care being provided by PSWs, frequency of care activities being provided by PSWs, and characteristics of the population receiving more complex tasks. Between January and April 2015, a review of 517 home‐care service user charts was undertaken in Ontario, Canada, to: (1) describe the range of tasks being performed by PSWs in home care, (2) identify tasks transferred by RHPs to PSWs, and (3) examine characteristics of service users receiving transferred care. Findings indicate that normally, PSWs provide personal and supportive care commensurate with their training. However, in approximately one quarter of care plans reviewed, PSWs also completed more complex care activities transferred to them by RHPs. Service users receiving transferred care were older and had higher levels of cognitive and functional impairment. Although there is potential for the expansion of home‐care services through increased utilisation of PSWs, healthcare leadership must ensure that the right provider is being utilised at the right time and in the right place to ensure safe and effective quality care. Thus, several actions are recommended: PSW core competencies be clearly articulated, processes used to transfer care activities from RHPs to PSWs be standardised and a team‐based approach to the delivery of home‐care services be considered. Utilisation of a team‐based model can help establish positive relationships among home‐care providers, provide increased support for PSWs, allow for easier scheduling of initial training and ensure regular reassessments of PSW competence among PSWs providing added skills.