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Biomedical subjects

S Naruse

Publications and source records attributed to S Naruse.

At least 19 recordsLinked to original sources

Metabolic and pathological effects of temporal lobe epilepsy in rat brain detected by proton spectroscopy and imaging.

The goal of these experiments was to test the hypothesis that in an animal model of temporal lobe epilepsy (TLE), magnetic resonance spectroscopic measurement of N-acetylaspartate (NAA) and other metabolites, together with magnetic resonance imaging, provides a sensitive in vivo method to localize and monitor the progression of neuronal cell death and gliosis. Seizures were induced in rats by unilateral hippocampal injection of kainate. Magnetic resonance measurements were made from 1 to 84 days using proton spectroscopic imaging (1H-MRSI), T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). The results were compared with findings on histological sections. Decreased NAA and creatine levels and increased apparent diffusion coefficient of water were found in the ipsilateral hippocampus after 14 days where neuronal loss and gliosis were observed. In the contralateral hippocampus a significant increase of choline level was observed. These results suggest that 1H-MRSI is a useful in vivo method for localizing neuronal loss and may also indicate additional pathological and metabolic alterations. In addition, DWI may be a useful method for in vivo detection of tissue alterations due to TLE.

Animals

Investigation of morphological change of lateral and midline fluid percussion injury in rats, using magnetic resonance imaging.

OBJECTIVE: Investigating the time course of morphological changes in experimental traumatic brain injury (TBI) in vivo helps to clarify the mechanism of TBI and develop new therapeutic modalities. We examined the morphological changes in experimental TBI, using magnetic resonance imaging (MRI) in a rat model. METHODS: We produced lateral fluid percussion injury (LFP) and midline fluid percussion injury (MFP) in rats, using the Yamaki fluid percussion device. The rats were divided into four groups: LFP, MFP, sham LFP, and sham MFP. MRI was performed with a 4.7-T magnetic resonance apparatus 2 days and 90 days after the induction of injury. T1-, T2-, and T2- weighted images were obtained using a surface coil. RESULTS: Hemorrhage, contusion, and brain edema in LFP models were detected on the 2nd day after injury, and the necrotic tissue was absorbed and replaced by cerebrospinal fluid on the 90th day. In MFP animals, we detected a small hemorrhage in the corpus callosum with minimal brain edema around the hemorrhage on the 2nd day after injury, and on the 90th day, enlarged ventricles and cisterns were observed, indicating brain atrophy. CONCLUSION: MRI, therefore, is useful for plotting morphological changes in experimental TBI in vivo. We report the novel and clinically important finding of brain atrophy after experimental TBI.

Animals

Pulsatile compression of the rostral ventrolateral medulla in hypertension.

The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by enhancing sympathetic outflow.

Animals

[The role of magnetic resonance spectroscopic imaging in patients with Parkinson's disease].

There are some single voxel proton magnetic resonance spectroscopy(MRS) of Parkinson's disease but no multi-voxel proton MRS. Proton magnetic resonance spectroscopic imaging(MRSI) is the multi-voxel method, from which we can obtain many spectra from many voxel at the same time. The distribution of each metabolite can be observed in the metabolite map. Although defects in oxidative phosphorylation have been reported from the studies of Parkinson's disease and dopaminergic cell death has been observed, the cause of Parkinson's disease is unknown. The spectra from the striatum and surroundings and the metabolite maps in MRSI will help to understand the pathogenesis of the disease.

Brain

Calcitonin gene-related peptide is a potent intestinal, but not gastric, vasodilator in conscious dogs.

The effects of human alpha-calcitonin gene-related peptide (alpha-CGRP), beta-CGRP, and vasoactive intestinal polypeptide (VIP) on left gastric (LGA) and superior mesenteric arterial (SMA) blood flow, heart rate and systemic arterial blood pressure were investigated in 6 conscious beagle dogs. Both intravenous injections of alpha-CGRP and beta-CGRP (5-200 pmol/kg) and infusion of alpha-CGRP (25-100 pmol/kg per h) induced a dose-related increase in SMA flow and a dose-related decrease in its resistance. At lower doses, alpha-CGRP was more potent than beta-CGRP, but their maximal responses were the same. alpha-CGRP and beta-CGRP had little effect on LGA flow. However, alpha-CGRP at 200 pmol/kg, but not beta-CGRP, stimulated gastroduodenal contractions that were associated with a phasic increase of LGA flow. Atropine inhibited gastric, but not duodenal, motor and circulatory responses to alpha-CGRP. Tachycardia and hypotension induced by beta-CGRP were significantly less than those by alpha-CGRP. VIP, on the other hand, increased mainly LGA flow. These results suggest that blood vessels of the small intestine of dogs are more sensitive to CGRP than those of the stomach, while the sensitivity to VIP is reversed.

Animals

NMR spectroscopic evidence that helodermin, unlike other members of the secretin/VIP family of peptides, is substantially structured in water.

The structure in water and additionally in 50% trifluoroethanol (TFE) solution of helodermin, an amidated peptide consisting of 35 amino acids, was elucidated by 2D 1H NMR spectroscopy initially from H alpha chemical shifts and qualitative NOE data. Detailed structures were calculated from the quantitative NOE data which were used as distance restraints in molecular dynamics and energy minimization calculations. Regions of stable secondary structure were defined from the resulting final peptide conformations using a new fitting program that takes into account the summed RMS differences between all structures for short segments of 2-5 residues in length. This procedure allows a reasonably objective method of defining the edges of stable structure. In contrast to other members of the secretin/VIP family of peptides, helodermin shows a defined secondary structure in water alone and possesses an alpha-helix from Glu-9 to Leu-23 that was further stabilized and slightly extended (Phe-6 to Ala-24) on addition of TFE. The N- and C-termini were unstructured in both solutions. Such features, in particular the observation of a linear helix 18 +/- 2 residues in length, are common to other members of the family and become more pronounced in hydrophobic environments. The data provide further circumstantial evidence that an alpha-helix conformation is necessary for receptor binding. The prolonged physiological action of helodermin, compared to its C-terminal deletion analogues and VIP, is at least in part due to the unusual stable secondary structure.

Amino Acid Sequence

Optimal conditions for collection of blood samples for assay of alpha 2-macroglobulin-trypsin complex-like substance (MTLS).

We have developed an enzyme-linked immunosorbent assay (ELISA) for the specific quantification of alpha 2-macroglobulin-trypsin complex-like substance (MTLS). To exclude artifacts in measured values of MTLS, the conditions for collection of blood samples are critical. In the present study, we have determined the optimal conditions for blood collection and investigated the role of MTLS as a clinical tool for diagnosis in pancreatitis. Results obtained are as follows: (1) MTLS levels of all sera were more than 10-fold higher than the corresponding plasma; (2) MTLS levels of heparinized plasma were the lowest among plasma with three anticoagulants (sodium citrate, sodium EDTA and heparin); (3) some kinds of blood collection tubes containing heparin were not suitable for the sampling; (4) MTLS values of plasma obtained by blood collection tubes containing Trasylol and sodium EDTA were demonstrated more stable and lower than those obtained by heparin tubes; and (5) under these conditions, we can exclude elevation of MTLS values caused by inappropriate blood sampling and find the time course of the elevation reflecting clinical course of a patient with acute pancreatitis and a patient after endoscopic retrograde cholangiopancreatography (ERCP). The optimal conditions for collection of blood samples were as follows. Blood sampling should be performed by blood collection tubes containing Trasylol (50 microliters/ml blood) and sodium EDTA (1.5 mg/ml blood). The samples were immediately stored at 4 degrees C and centrifuged at 3,000 rpm for 15 min. The plasma were stored in plastic tubes at 4 degrees C until assayed.

Anticoagulants

Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease.

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.

Adult

Effects of a bradykinin receptor antagonist (HOE140) on taurocholate-induced acute pancreatitis in rats.

The effect of a potent and long-acting bradykinin B2-receptor antagonist (HOE140) on acute pancreatitis induced by retrograde infusion of trypsin and taurocholate into the pancreatic duct was studied in rats. HOE140 was administered subcutaneously immediately before and 3 h after the induction of pancreatitis and the systemic blood pressure, ascites volume, serum amylase, 24-h survival rate, and pathology of the pancreas were evaluated. Plasma concentrations of bradykinin increased significantly 15 min after the induction of pancreatitis and decreased to basal levels at 90 min. HOE140 (0.1 mg/kg) alleviated hypotension developing immediately after the induction of pancreatitis and reduced the ascites volume. The 24-h survival rate in rats treated with 0.1 mg/kg HOE140 (70.3%) was significantly higher than that in controls (35.6%). Treatment with 0.01, 0.3, 1.0, and 3.0 mg/kg of HOE140, however, had no beneficial effect on the survival rate. Ascites volume, serum amylase, and pathology of the pancreas at 24 h were not improved by treatment with HOE140. These data suggest that HOE140 may improve the survival rate by maintaining hemodynamics in the early stage of experimental acute pancreatitis.

Acute Disease

Irradiation effects on the metabolism of metastatic brain tumors: analysis by positron emission tomography and 1H-magnetic resonance spectroscopy.

To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The tumor origins were lung cancer in three patients and breast cancer in two. Treatment volume was 0.4-10.1 cm3 (mean: 5.5 cm3). The marginal dose to the tumor was 24-30 Gy (mean: 26.2 Gy). The follow-up period was 5-19 months (mean: 13.4 months). No patients had conventional whole-brain radiation therapy. 18F-fluoroboronophenylalanine (18FBPA) or 18F-fluorodeoxyglucose (18FDG) were used as tracers for the PET study. Using 1H-MRS, several metabolites were simultaneously measured in metastatic brain tumor and adjacent brain. In the PET study of the representative case, the uptake rate of 18FBPA that is actively transported to the tumor decreased markedly 15 days after radiosurgery and continued to decrease thereafter. In the 1H-MRS study, choline, which is characteristically high in metastatic brain tumors, also decreased over time. In two cases with suspected radiation injury, the enhanced region, which was decreased in size in early follow-up, enlarged progressively and was accompanied by edema. However, 18FBPA and 18FDG were not transported to the enhanced region. The peak of free lipid, which might show destruction of the cell membrane, was recognized in the enhanced region and adjacent brain in these cases. This study revealed that radiation effects on the metabolism of metastatic brain tumors occur at an early stage after radiosurgery and continue over several months. In particular, in the case of radiation injury, PET and 1H-MRS studies made it possible to distinguish between regrowth of the tumor and radiation injury.

Aged

Cerebral MRI and spectroscopy in Sjögren-Larsson syndrome: case report.

We report MRI and MRS of the brain in a patient with Sjögren-Larsson syndrome (SLS) in whom fatty alcohol oxidoreductase (FAO) deficiency has been verified. MRI showed periventricular lesions, high intensity on T2-weighted and low intensity on T1-weighted images at trigones of the lateral ventricles. 1H-MRS of these lesions revealed high lipid and low N-acetyl aspartate peaks. We presume such lipids in periventricular lesions with high T2 signal may be pathognomonic of SLS.

Adult

Effect of gastrin-releasing peptide (GRP) on guinea pig gallbladder contraction in vitro.

Few studies have reported the effects of gastrin-releasing peptide (GRP)/bombesin on the guinea pig gallbladder, and the results are contradictory. Because such contradictory results may, in part, be due to technical factors, we investigated the effect of GRP on guinea pig gallbladder smooth muscle, using an improved horizontal organ bath. The guinea pigs were killed and the gallbladder was removed. Four longitudinal muscle strips (2 x 12 mm) were suspended in Krebs-Ringer solution at 37 degrees C and aerated with 95% O2 and 5% CO2. The mechanical activity of the strips was recorded isotonically by displacement-voltage transducers, via L-arms, to which a piezoelectric element with a frequency of 100 Hz and movement of 50 microns was applied. GRP contracted gallbladder muscle strips dose dependently, but the calculated maximal response was 22.4% and 20.1% of the acetylcholine- and cholecystokinin octapeptide (CCK8)-induced responses, respectively. The GRP-induced contraction was unaffected by the muscarinic blocker, atropine, or by the CCK receptor antagonist, loxiglumide. It is concluded that GRP weakly, but apparently directly, stimulates guinea pig gallbladder contraction.

Acetylcholine

Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic pancreatitis.

Lactoferrin and pancreatic stone protein (PSP) are thought to be closely related to pancreatic stone formation in chronic pancreatitis. However, the results reported so far have not been conclusive. To reevaluate the pathological importance of PSP in chronic pancreatitis, compared to lactoferrin, levels of PSP were determined by applying an immunoassay specific to PSP to pure pancreatic juice taken from a total of 52 patients. The patients consisted of 16 controls, 19 chronic pancreatitis patients (13 noncalcified and 6 calcified), and 17 probable cases of pancreatitis. The monoclonal antibody PSP antagonist used in the study recognizes both forms of the protein, PSP S1 and S2-5, with equal effectiveness. No significant reduction of PSP was observed in either calcified (mean +/- SEM, 111 +/- 30 micrograms/mg and 24 +/- 3 micrograms/mg protein) or noncalcified (305 +/- 133 and 97 +/- 47) chronic pancreatitis patients compared with controls (85 +/- 23 and 34 +/- 16). PSP levels did not decrease, at least not in the complete forms of the protein found in chronic pancreatitis. PSP antibody and assay results indicated that a reduction of PSP S2-5 alone could not be ruled out in chronic pancreatitis either.

Adult

Activation of trypsinogen in experimental models of acute pancreatitis in rats.

Trypsinogen activation peptide (TAP) concentration and alpha 2-macroglobulin-trypsin complex (alpha 2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and alpha 2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), alpha 2M-T activity in serum was significantly lower than that in nontreated controls (mean +/- SEM, 20.8 +/- 1.43 U/L in the FUT group vs 79.1 +/- 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 +/- 0.8 ng/ml) than in the lethal group (25.9 +/- 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.

Acute Disease

Non-invasive measurement of brain activity using functional MRI: toward the study of brain response to acupuncture stimulation.

We studied functional MRI in 15 male and 13 female normal volunteers on a clinical MRI system using gradient echo sequence. During the experiments, brain activation was induced by grasping the unilateral hand once or twice a second for motor tasks. A localized increase of MRI signal in the contralateral motor cortex was observed in 17 out of 21 cases (81%) under right hand motor task and 11 out of 21 cases (52%) under left hand motor task. The application of this method may be useful to evaluate brain response to acupuncture.

Acupuncture Therapy