BackgroundRecently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection.Methods and FindingsPlasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling.ConclusionsThese findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods.

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Blood pressure varies in relation to factors such as physical activity, body position, ambient temperature, and autonomic nervous system activity. Therefore, we have developed a portable multibiomedical (PMB) recorder that monitors five parameters: indirect blood pressure, physical activity, body position, ambient temperature, and RR interval of the electrocardiogram. In the present study, we applied the PMB recorder over a 24-hour period to study the effect of insufficient sleep on blood pressure in subjects doing extensive overtime work. The parameters listed above were measured by the PMB recorder throughout a normal workday (mean period of sleep, 8 hours) and throughout a day with insufficient sleep (mean period of sleep, 3.6 hours) in 18 male technical workers aged 23 to 48 years old. Blood pressure (mean systolic/diastolic pressure +/- SD) significantly increased the day after a sleep-insufficient night (129 +/- 8/79 +/- 6 mm Hg) compared with the day after a normal night (123 +/- 8/76 +/- 7 mm Hg, P<.05). However, ambient temperature, mean number of steps per minute, and percentage of time spent in a standing position showed no significant difference between these days. Spectral analysis of RR intervals showed that the ratio of the low-frequency component on the RR power spectrum (0.05 to 0.15 Hz) to the high-frequency component (0.15 to 0.40 Hz) was higher on the sleep-insufficient day (2.17 +/- 0.37 versus 1.81 +/- 0.37), as was the urinary excretion of norepinephrine (P<.05). Heart rate was significantly higher on the sleep-insufficient day (81 +/- ll versus 76 +/- 8 beats per minute), after the data of two subjects with abnormal levels of physical activity were excluded (P<.Ol). These data suggest that lack of sleep may increase sympathetic nervous system activity on the following day, leading to increased blood pressure. The PMB recorder was useful for precisely evaluating the relationship between blood pressure and environmental factors.

Previous studies, including our own, have demonstrated that muscle sympathetic nerve activity (MSNA) is increased in patients with essential hypertension compared with normotensive subjects. However, the features of sympathetic nerve activity are still unknown in secondary hypertension. We examined MSNA in eight patients with renovascular hypertension and in 11 patients with primary aldosteronism. Twenty patients with essential hypertension and 20 normotensive subjects who were age-matched to the patients with renovascular hypertension and those with primary aldosteronism were also studied. The MSNA of a bundle of the tibial nerve was recorded by microneurography in supine subjects and expressed as both burst rate (bursts/min) and burst incidence (bursts/100 heart beats). Plasma renin activity and the plasma concentration of angiotensin II and aldosterone were also measured. MSNA was increased in the patients with renovascular hypertension compared with the patients with primary aldosteronism and those with essential hypertension and the normotensive subjects (p<0.01 for each). MSNA was decreased in the patients with primary aldosteronism compared with those with essential hypertension (p<0.01), and it was smaller than in the normotensive subjects (p<0.l). Furthermore, MSNA, plasma renin activity, and the plasma concentration of angiotensin II decreased significantly in five patients with renovascular hypertension 4-10 days after successful percutaneous renal angioplasty. Thus, the changes in MSNA seem to characterize the patbophysiology of renovascular hypertension and primary aldosteronism. Activation of the renin-angiotensin system may be involved in the increase in the central outflow of sympathetic nerve activity, thus exacerbating hypertension in patients with renovascular hypertension. (Hypertension 1991;17:1057-1062) N eurogenic mechanisms have often been implicated in the pathogenesis of hypertension. Although the plasma concentration of norepinephrine has been used as a rough index of overall sympathetic nerve activity, its pathophysiological implications need careful evaluation since the plasma concentration of norepinephrine is determined by many factors, such as the reuptake and metabolic degradation of norepinephrine and its spillover from the nerve endings.1 ' 2 Accordingly, we have investigated sympathetic tone by directly recording the muscle sympathetic nerve activity (MSNA) contained in a bundle of the tibial nerve using a microneurographic technique in the conscious human.3 -8 Our previous studies have demonstrated that the baroreflex control of sympathetic

To investigate the pathophysiological role of the sympathetic nervous system in essential hypertension, this study recorded the muscle sympathetic nerve activity (MSNA) of the tibial nerve and examined the age-related changes in patients with essential hypertension and in normotensive persons. There were 43 normotensive subjects (16-69 years old) and 63 patients with essential hypertension (18-67 years old) in the study. The MSNA at rest, recorded by microneurography, was evaluated by burst rate (bursts/min), burst incidence (bursts/100 heart beats), and spike frequency (spikes/min). The MSNA recording showed a high reproducibility with a correlation coefficient of 0.86 (p<0.0l) in repeated studies. The MSNA was significantly greater in the hypertensive patients than in the normotensive subjects, irrespective of activity units (p<0.0l), and this finding was consistent in the young (30 years old or less), middle-aged (31-50 years old), and old groups (51 years old or more). Furthermore, MSNA showed a significant positive correlation with age both in the normotensive subjects (r=0.43, p<0.01 for burst rate; r=0.49, /?<0.01 for burst incidence; and r=0.50, p<0.01 for spike frequency) and in the hypertensive patients (r=0.40,/><0.01 for burst rate; r=0.44,p<0.01 for burst incidence; and r=0.40, /><0.01 for spike frequency). Although there was a significant positive correlation between plasma norepinephrine concentration and MSNA in the hypertensive patients and the normotensive subjects, the difference in plasma norepinephrine concentration between the two groups was not significant at any age level. These results indicate that sympathetic nerve activity is increased in patients with essential hypertension at any age level and plays a long-term role in the development and maintenance of blood pressure elevation. (Hypertension 1989; 13:870-877)