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Biomedical subjects

S Kearney

Publications and source records attributed to S Kearney.

6 recordsLinked to original sources

Absence of mutations in the VHL gene but frequent loss of heterozygosity at 3p25-26 in non-small cell lung carcinomas.

In this study we have examined 79 primary non-small cell lung tumours for the presence of mutations of the VHL gene as well as for allelic imbalance at the gene surrounding loci. While allelic imbalance was found in 83% of specimens, frequently affecting the whole 3p25-p26 region, no mutations were detected in the VHL coding region. The fractional regional loss (FRL) was significantly higher in squamous cell carcinomas (0.746) than adenocarcinomas (0.493) (Wilcoxon P=0.002). This is the first investigation of the VHL gene mutational status in primary lung tumours. Our results indicate that mutation is not a common means of VHL inactivation in NSCLC.

Adenocarcinoma↗

Modified peptide antagonists of interleukin 5 exhibit extended in vivo persistence but restricted species specificity.

AF18748 is disulphide-linked homodimeric peptide with 19 amino acids in each chain that antagonises the action of the eosinophil-specific cytokine, interleukin 5 (IL-5). We have generated a set of N-terminally truncated peptides derived from AF18748 and demonstrated that the first five amino acids of the peptide do not contribute to receptor binding activity. The shortened peptide blocked IL-5-dependent adhesion of eosinophils with an IC(50)of 350 pM, and had no effect on stimulation by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha or fMet-Leu-Phe. The peptides were rapidly broken down in mouse plasma through cleavage of a single chain of the dimer. However, this breakdown did not correlate with loss of biological activity, indicating that the asymmetric peptide fragment retains full receptor binding capacity. The activity of AF18748 disappeared rapidly from the blood following intravenous injection into mice. Coupling of polyethylene glycol to the N-terminus of AF18748 resulted in a moderate loss in biological potency (IC(50)30 nM), but the resulting conjugate persisted in the circulation for more than 8 h after injection. Despite its high potency at the human IL-5 receptor, AF18748 was unable to antagonise the activity of IL-5 on murine B13 cells, or on canine eosinophils, indicating that the peptide is highly specific for the human IL-5 receptor.

Amino Acid Sequence↗

Speech, cognition, and imaging studies in congenital ocular motor apraxia.

Detailed neurological, speech and language, psychological, and neuroimaging studies were carried out in eight children with the diagnosis of congenital ocular motor apraxia. The neurological examination showed clinical evidence of cerebellar vermis abnormality (hypotonia and truncal ataxia) in all cases. Neuroimaging studies suggested that the site of neuropathological disturbance of congenital ocular motor apraxia was the inferior vermis. Half of the subjects had associated speech apraxia. The most likely location of brain disturbance, which was responsible for the speech apraxia, was also an as yet undefined area of the vermis. Psychological testing consistently revealed visual-spatial difficulties. These may have been secondary to cerebellar pathology or to developmentally inappropriate sensory input caused by the abnormal saccades. Children with speech apraxia appear to be slightly more affected neurologically than those with normal speech.

Apraxias↗

Lithium mania: play and learn.

The authors describe an instructional game, Lithium Mania, which they developed to assist in teaching psychiatric clients who were taking lithium about their medication. This game can be used in a formal or recreational setting. The goal of learning made fun was to increase compliance and decrease recidivism.

Games, Experimental↗

The use of adapted leisure materials to reinforce correct head positioning in a brain-injured adult.

This study aims to highlight the possible use of adapted leisure materials in the modification of behavioural responses within the brain-injured population. Single-case methodology was used to evaluate the effectiveness of contingent reinforcement in promoting head posture in an adult brain-injured male. A microswitch was implanted within a headband worn by the subject, attached to a portable radio and positioned such that correct head posture operated the switch, completed the electric circuit and activated the music. The target behaviour was defined as the percentage of time in a walking programme where correct head posture was maintained. The experimental procedure incorporated an A-BC-B-BC-A design and represented the following phases: (A) baseline; (BC) headband + music and (B) headband, no music. A follow-up assessment was also undertaken 1 month later. Overall, statistical analysis revealed a significant increase in the target behaviour and that this improvement was directly contingent on the provision of music inforcement. Results are discussed in further detail and the clinical significance of this finding, over and above the statistical significance, is highlighted in terms of this individual's rehabilitation.

Adult↗