The importance of pH adjustment for preventing fibrin glue dissolution in the stomach: an in vitro study.

Combined use of fibrin glue and polyglycolic acid (PGA) sheets has attracted attention as a preventive measure for complications associated with endoscopic submucosal dissection. However, fibrin glue is a protein that may be dissolved by gastric acid. We evaluated the effect of artificial gastric acid on fibrin clot. The dissolution time of three layers of fibrin glue with PGA sheets was measured in five groups (pH 1.2, 2.0, 4.0, 5.5, and 6.0 with pepsin). Measurements of three samples per group were made. The mean number of the remaining layers at each measurement point was observed for 168 h. The time to complete dissolution of the three layers of fibrin gel in the three samples was 2.5 h at pH 1.2, 5 h at pH 2.0, 24 h at pH 4.0, and 48 h and 6 h at pH 5.5. In order to maintain fibrin glue in the stomach for a long period, there was a need to avoid pepsin activation secondary to acidification of gastric juice. The use of strong antacids is recommended.

An autoantibody against N(ε)-(carboxyethyl)lysine (CEL): possible involvement in the removal of CEL-modified proteins by macrophages.

Advanced glycation end products (AGEs) are believed to play a significant role in the development of diabetic complications. In this study, we measured the levels of autoantibodies against several AGE structures in healthy human plasma and investigated the physiological role of the autoantibodies. A high titer of the autoantibody against N(ε)-(carboxyethyl)lysine (CEL) was detected in human plasma compared with other AGE structures such as CML and pentosidine. The purified human anti-CEL autoantibody reacted with CEL-modified human serum albumin (CEL-HSA), but not CML-HSA. A rabbit polyclonal anti-CEL antibody, used as a model autoantibody against CEL, accelerated the uptake of CEL-HSA by macrophages, but did not enhance the uptake of native HSA. Furthermore, when (125)I-labeled CEL-HSA was injected into the tail vein of mice, accumulation of (125)I-CEL-HSA in the liver was accelerated by co-injection of the rabbit anti-CEL antibody. These results demonstrate that the autoantibody against CEL in plasma may play a role in the macrophage uptake of CEL-modified proteins.

Effect of reactive-aldehydes on the modification and dysfunction of human serum albumin.

Advanced glycation end products (AGEs) are generated not only from glucose but also from several aldehydes such as methylglyoxal, glyoxal, and glycolaldehyde. The aim of the present study was to investigate the effect of several aldehydes on human serum albumin (HSA) in terms of the physicochemical properties and formation of AGE structures. HSA modified with methylglyoxal, generated by the glycolysis pathway and degradation of the Schiff base, showed the highest increase in the molecular weight and net negative charge, whereas glucose modification caused a small increase in the molecular weight even incubation for after 4 weeks. N(epsilon)-(carboxymethyl)lysine (CML), N(epsilon)-(carboxyethyl)lysine (CEL), and imidazolone increased in modified HSA in correlation with their lysine and arginine modification, whereas high amounts of GA-pyridine was detected in HSA modified with glycolaldehyde. Furthermore, the binding ability of HSA to warfarin and ketoprofen was more effectively decreased by methylglyoxal modification than the other aldehydes. These results indicated that changes in the physicochemical properties and the formation of AGE structures are highly dependent on the aldehydes.

Usefulness of antibodies for evaluating the biological significance of AGEs.

Polyclonal and monoclonal antibodies have been widely applied to demonstrate the presence of advanced glycation end products (AGEs) in vivo. However, our previous study showed that monoclonal anti-AGE antibody (6D12) and polyclonal anti-N epsilon-(carboxymethyl)lysine (CML) antibody recognize not only CML but also N epsilon-(carboxyethyl)lysine (CEL), thus indicating that we should pay attention to the specificity of the antibodies. As a result, we prepared specific monoclonal antibodies against CML, CEL, N omega-(carboxymethyl)arginine (CMA), and S-(carboxymethyl)cysteine (CMC). Our immunochemical study using anti-CMA antibody demonstrated that the CMA content increased in a time-dependent manner when collagen was incubated with glucose, indicating that immunological quantification using the specific antibody is especially useful for measuring an acid-labile AGE structure, such as CMA. Monoclonal antibody is also applied to identify a novel biological marker in pathological lesions. We prepared antibody libraries against proteins modified with aldehydes, such as glyoxal, methylglyoxal, and glycolaldehyde (GA), and one antibody, GA5, which specifically reacts with the GA-modified protein that is recognized in human atherosclerotic lesions. Following successive high-performance liquid chromatography purification, the GA5-reactive compound was isolated and its chemical structure was found to be 3-hydroxy-4-hydroxymethyl-1-(5-amino-5-carboxypentyl) pyridinium cation, which was named GA-pyridine. Taken together, these results demonstrate that a specific antibody is a powerful tool for analyzing novel biomarkers, formation pathways, and the efficacy of AGE inhibitors.

Morphofunctional organization in three patients with unilateral polymicrogyria: combined use of diffusion tensor imaging and functional magnetic resonance imaging.

We examined the fiber organization of the brain in three patients with unilateral polymicrogyria (PMG) using diffusion tensor imaging (DTI) in combination with functional magnetic resonance imaging (fMRI). DTI revealed altered fiber tract architecture in patients with PMG. Long projection fibers, such as the corticospinal tract, were reduced the most, whereas long association fibers were less affected. The diminution of the fiber tracts was relevant to the loss of functionality of the PMG-affected cortex. Our preliminary study suggests that the combination of DTI and fMRI reinforces the clinical assessment of functionality in PMG.

Multimodal assessment of cortical activation during apple peeling by NIRS and fMRI.

An intriguing application of neuroimaging is directly measuring actual human brain activities during daily living. To this end, we investigated cortical activation patterns during apple peeling. We first conducted a pilot study to assess the activation pattern of the whole lateral cortical surface during apple peeling by multichannel near-infrared spectroscopy (NIRS) and detected substantial activation in the prefrontal region in addition to expected activations extending over the motor, premotor and supplementary motor areas. We next examined cortical activation during mock apple peeling by simultaneous measurement using multichannel NIRS and functional magnetic resonance imaging (fMRI) in four subjects. We detected activations extending over the motor, premotor and supplementary motor areas, but not in the prefrontal cortex. Thus, we finally focused on the prefrontal cortex and examined its activation during apple peeling in 12 subjects using a multichannel NIRS. We subsequently found that regional concentrations of oxygenated hemoglobin significantly increased in the measured region, which encompassed portions of the dorsolateral, ventrolateral and frontopolar areas of the prefrontal cortex. The current study demonstrated that apple peeling as practiced in daily life recruited the prefrontal cortex but that such activation might not be detected for less laborious mock apple peeling that can be performed in an fMRI environment. We suggest the importance of cortical study of an everyday task as it is but not as a simplified form; we also suggest the validity of NIRS for this purpose. Studies on everyday tasks may serve as stepping stone toward understanding human activities in terms of cortical activations.

FASCINATE: a pulse sequence for simultaneous acquisition of T2-weighted and fluid-attenuated images.

A pulse sequence that enables simultaneous acquisition of T2-weighted and fluid-attenuated images is presented. This sequence is referred to as FASCINATE (Fluid-Attenuated Scan Combined with Interleaved Non-ATtEnuation). In this new technique, the inversion pulse of conventional fast fluid-attenuated inversion recovery (FLAIR) is replaced with a fast spin echo (FSE) acquisition that has an additional 180(y)-90(x) pulse train for driven inversion. By using appropriate scan parameters, the first part of the sequence provides T2-weighted images and the second part provides fluid-attenuated images, thus allowing simultaneous acquisition in a single scan time comparable to that of fast FLAIR. FASCINATE was compared with conventional scanning techniques using a normal volunteer and a patient. A signal simulation was also conducted. In the human study, both T2-weighted and fluid-attenuated images from FASCINATE showed the same image quality as conventional images, suggesting the potential for this technique to replace the combination of fast FLAIR and T2-weighted FSE for scan time reduction.

Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10-20 system oriented for transcranial functional brain mapping.

The recent advent of multichannel near-infrared spectroscopy (NIRS) has expanded its technical potential for human brain mapping. However, NIRS measurement has a technical drawback in that it measures cortical activities from the head surface without anatomical information of the object to be measured. This problem is also found in transcranial magnetic stimulation (TMS) that transcranially activates or inactivates the cortical surface. To overcome this drawback, we examined cranio-cerebral correlation using magnetic resonance imaging (MRI) via the guidance of the international 10-20 system for electrode placement, which had originally been developed for electroencephalography. We projected the 10-20 standard cranial positions over the cerebral cortical surface. After examining the cranio-cerebral correspondence for 17 healthy adults, we normalized the 10-20 cortical projection points of the subjects to the standard Montreal Neurological Institute (MNI) and Talairach stereotactic coordinates and obtained their probabilistic distributions. We also expressed the anatomical structures for the 10-20 cortical projection points probabilistically. Next, we examined the distance between the cortical surface and the head surface along the scalp and created a cortical surface depth map. We found that the locations of 10-20 cortical projection points in the standard MNI or Talairach space could be estimated with an average standard deviation of 8 mm. This study provided an initial step toward establishing a three-dimensional probabilistic anatomical platform that enables intra- and intermodal comparisons of NIRS and TMS brain imaging data.

[4D-MRI using the synchronized sampling method (SSM)].

A synchronized sampling method (SSM) was developed for the study of voluntary movements by combining the electrocardiographic (ECG) gating method with an external triggering device, and four-dimensional magnetic resonance imaging (4D-MRI) at a rate of 30 frames per second was accomplished by volumetric imaging with the SSM. This method was first applied to the motion imaging of articulatory organs during repetitions of a Japanese five-vowel sequence, and the dynamic change in vocal tract area function was demonstrated with sufficient temporal resolution. This paper describes the methodology, applicability, and limitations of 4D-MRI with the SSM.