A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma.

We have identified an antigen recognized on a human melanoma by autologous cytolytic T lymphocytes. It is encoded by a gene that is expressed in many normal tissues. Remarkably, the sequence coding for the antigenic peptide is located across an exon-intron junction. A point mutation is present in the intron that generates an amino acid change that is essential for the recognition of the peptide by the anti-tumor cytotoxic T lymphocytes. This observation suggests that the T-cell-mediated surveillance of the integrity of the genome may extend to some intronic regions.     

Development of brain damage after neonatal hypoxia-ischemia: Excitatory amino acids and cysteine

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.     

Photopatch testing: a consensus methodology for Europe

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.     

Functional parameters before and after parathyroidectomy: a prospective, randomized long-term trial on different rat strains.

For clinical controls before and after parathyroidectomy and for evaluation of the function of transplants of parathyroid tissue, it is necessary to establish standard values of relevant laboratory parameters for donor and recipient animals as well as for different types of nutrition. Since no such data are yet available, it was the purpose to define such standards. In a prospective randomized trial on 400 rats of the Dark Agouti (DA) and Lewis strain, different functional laboratory parameters such as total calcium, intact parathyroid hormone, phosphate, 1.25-dihydroxyvitamin D, and alkaline phosphatase were measured under a standard and low calcium diet over a period of 40 weeks. Two hundred of these animals underwent a parathyroidectomy four weeks after the beginning of the study and specimens were evaluated histologically. For all eight different study groups normal values could be defined within tight limits for parameters which describe the function of the parathyroid gland or elements of calcium metabolism under different conditions. The optimal conditions for a transplantation model of parathyroid glands were established. Lewis-rats were identified as the ideal donor and DA rats as the better recipient animals. These data can serve as reference values for future studies on transplantation of the parathyroid without immunosuppression.     

Evaluation of education program developments: illustration of the research and development cycle

The Research and Development (R and D) cycle is a program development model used to translate research findings into educational programs or products ready for use in the field. The R and D cycle is illustrated by describing its application to Effective Patient Teaching, a course on teaching skills for health professionals. Evaluation is a continuing part of program development. Evaluation methods need not follow a rigid formula; methods will generally change with the stages of program development and the evaluation purposes.     

Laryngeal Transplantation in 2005: A Review

There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full-scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.     

Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.     

Human brainstem auditory-evoked potentials in deep experimental diving to pressures up to 62.5 bar.

The neural mechanisms underlying the high pressure neurologic syndrome (HPNS), which limit man's safe advance to extreme diving depths, are still unclear. This work was aimed at a better understanding of HPNS through study of brainstem auditory-evoked potentials (BAEP). BAEP were repeatedly recorded within 2 experimental chamber dives, Titan VIII (2 divers, maximum depth of 560 msw, compression time to bottom 109 h) and Titan XI (3 divers, maximum depth of 615 msw, compression time to bottom 240 h). Prolongation of the IV/V-complex occurred in 2 divers upon reaching 525 msw during Titan VIII compression and was accompanied by vestibular disturbances and amplitude increases of finger tremor. Both categories of changes--clinical signs and IV/V delay--gradually diminished during a 4-day stay at 545 msw, suggesting that they depended on excessive compression rates and insufficient acclimation time. Longer holding times at intermittent depths during Titan XI clearly reduced both HPNS symptoms and magnitude of prolongation of IV/V latencies. Wave I and wave III latency did not significantly change, pointing to a suppression of pontomesencephalic transmission. We infer that pressure suppresses synaptic transmission or triggers an increase of cortical or subcortical efferent inhibitory modulation of upper pontine and midbrain auditory afferents. Postdive controls revealed no persistent changes of BAEP measures in either the Titan VIII or XI divers.