[Chairmen's Introductory Remarks].

The topic of this symposium "advancement of biomarkers" focused on biomarkers and laboratory medicine. The following 4 papers were presented: 1. Liver disease diagnoses and new biomarkers, 2. Atherosclerosis and new biomarkers, 3. Leukemia biomarkers, and 4. A new inhibitory factor against erythropoietin for diagnosis and assessment of anemia. As these titles suggest, this symposium covered broad fields of medical practice. All presentations demonstrated the marked development of new biomarkers in association with advanced technology along with improved understanding of disease pathologies. These frontier research areas related to biomarkers lead to the expectation of further novel practical biomarkers in the future. Further explora- tion in all fields for biomarker development will be performed, leading to new clinically practical diagnostic tools. Laboratory medicine will further contribute through the development of novel diagnostic technologies. [Review].

[Development of Rapid Assay of Transthyretin in Whole Blood].

Transthyretin (TTR), a rapid turnover protein with a half-life of 2 days, which is shorter than that of albumin, is considered to be a sensitive indicator of a patient's nutritional status. We have newly developed a rapid assay of TTR by immunochromatography (IC) using samples of whole blood as well as serum at volumes of 10 µL. The fundamental performance was evaluated using control sera. In addition, whole blood samples were measured by IC and the results were compared with measured levels of plasma samples by turbidimetry and those of sera by nephelometry. The limit of quantification was 8.3 mg/dL. The linearity was 8.7-35.4 mg/dL. The reproducibility was 6.1-8.6% coefficient of variation. Bilirubin, hemolysis, chyle, and rheumatoid factor did not influence the measured levels. An increase of 1% in hematocrit resulted in a decrease of 1% in the measured levels. The correlation between IC (y) and nephelometry (x) was determined to be y = 0.927x+2.62 (r = 0.935, n = 64). The newly developed IC showed good performance and it was suggested that IC would be useful for nutrition monitoring as point of care test.

Electrical field distribution of Change-N1 and its prepulse inhibition.

An abrupt change in a sound feature (Test) in a continuous sound elicits an auditory evoked potential, peaking at approx. 100-180 ms (Change-N1) after the change onset. Change-N1 is attenuated by a preceding weak change stimulus (Prepulse), in the phenomenon known as prepulse inhibition (PPI). In this electroencephalographic study, we compared these two indexes among scalp electrodes. Change-N1 was elicited by an abrupt 10-dB increase in sound pressure in repeats of a 70-dB click sound at 100 Hz and was recorded using 22 electrodes in 31 healthy subjects. The prepulse was a 10-dB decrease in three consecutive clicks at 30, 40, and 50 ms before the Test onset. Four stimuli (Test alone, Test with Prepulse, Prepulse alone, and background alone) were presented randomly through headphones at an even probability. The results demonstrated that: (1) Electrodes at the frontal/central midline were reconfirmed to be suitable to record Change-N1; (2) Change-N1 showed right-hemisphere predominance; (3) There was no difference in the %PPI among regions (prefrontal/frontal/central) and hemispheres (midline/left/right); and (4) the Change-N1 amplitude and its PPI at prefrontal electrodes were positively correlated with those at the frontal electrodes. These results support the use of Change-N1 and its PPI as a tool to evaluate the change detection sensitivity and inhibitory function in individuals. The use of prefrontal electrodes can be an option for a screening test.

Weaker prepulse exerts stronger suppression of a change-detecting neural circuit.

Change-N1 peaking 90-180 ms after changes in a sound feature of a continuous sound is clearly attenuated by a preceding change stimulus (called a "prepulse"). Here, we investigated the effects of a preceding decrease in sound pressure on the degree of inhibition of the subsequent Change-N1 amplitude. Using 100-Hz click train sounds, we obtained Change-N1s from 11 healthy volunteers. The two types of test stimuli were an abrupt 10-dB increase from the baseline (70 dB) and the insertion of a 0.45-ms inter-aural time difference in the middle of the sound. Three consecutive clicks at 30, 40, and 50 ms before the change onset that was used as a prepulse were weaker than the background by 5 or 10 dB. The Change-N1 elicited by the two test stimuli was attenuated more strongly by the weaker prepulse, which was not congruent with the theory that the inhibition of the subsequent sensory/sensory-motor processing depends on the sound pressure level of a prepulse. These results suggest that a change in any type of sound feature elicits a change-related response that is inhibited by any type of preceding change stimulus, which reflects auto-inhibition of the change-responding circuit.