ApoE-epsilon 4 and early-onset Alzheimer's.
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Age of Onset↗
Biomedical subjects
S Naruse
Publications and source records attributed to S Naruse.
Effect of exercise on gastroduodenal functions in untrained dogs.
Eight dogs were used to study the effect of 2 h submaximal (60-70% of maximal heart rate) exercise on gastric secretion and gastroduodenal motor function in fasted and fed states. Fasting gastric acid and pepsin secretion were not affected by exercise. Postprandial gastric acid secretion was significantly depressed (p < 0.05) during the second hour of exercise. Postprandial pepsin secretion was significantly decreased in both resting and exercised states. Gastric emptying of a liquid meal (protein 23.5%, fat 3.5%, carbohydrate 66.5% [w/w], 390kcal) was significantly delayed by exercise (p < 0.05). The migrating motor complex (MMC) was not observed during exercise, however, upon cessation of exercise, MMCs appeared at an expected 214 +/- 14 min after the pre-exercise MMC. Exercise did not affect the mean motor activity of the stomach but significantly increased the mean frequency (p < 0.05) and amplitude (p < 0.01) of the contractions in the duodenum, in the fasted and fed states, respectively. In conclusion, exercise lasting more than 1 h significantly depressed postprandial gastric secretion and significantly delayed gastric emptying (p < 0.05). Duodenal motor activity was significantly increased (p < 0.05 and p < 0.01) by exercise in both the fasted and fed states.
Animals↗
Linear and conformation-dependent antigenic sites on the nucleoprotein of rabies virus.
A set of 29 monoclonal antibodies (MAbs) specific for the rabies virus nucleoprotein (N protein) was prepared and used to analyze the topography of antigenic sites. At least four partially overlapping antigenic sites were delineated on the N protein of rabies virus by competitive binding assays. Indirect immunofluorescent antibody tests using MAbs with a series of rabies and rabies-related viruses showed that epitopes shared by various fixed and street strains of rabies virus were mainly localized at antigenic sites II and III, while epitopes representing the genus-specific antigen of Lyssavirus were widely presented at sites I, III and IV. All but one of seven MAbs specific for antigenic sites I, IV and bridge site (I and II) reacted with the antigen that had been denatured by sodium dodecyl sulfate or 2-mercaptoethanol, as well as with the denatured N protein in Western blotting assays. However, none of the MAbs against antigenic sites II and III reacted with the denatured antigen. These data indicate that antigenic sites I and IV, and sites II and III on the N protein of rabies virus are composed of linear and conformation-dependent epitopes, respectively.
Animals↗
Regulation of pancreatic polypeptide release is mediated through M3 muscarinic receptors.
The purpose of this study was to determine the regulation of pancreatic polypeptide (PP) release by using pirenzepine (a specific M1 muscarinic receptor antagonist), 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP, a specific M3 muscarinic receptor antagonist), atropine (a nonspecific muscarinic receptor antagonist), and loxiglumide (cholecystokinin, CCK, receptor antagonist) in dogs. In conscious dogs with chronic gastric and duodenal fistulas, release of PP and exocrine pancreatic secretion were stimulated by constant intravenous infusion of CCK-8 (200 ng/kg/h). Graded doses of pirenzepine (0.18-4.7 mmol/kg/h), 4-DAMP (6.7-180 nmol/kg/h), or atropine (0.89-24 nmol/kg/h) dose-dependently reduced plasma PP responses to CCK-8 without influence on exocrine pancreatic secretion. ID50 calculated from these results were 492 +/- 150 nmol/kg/h for pirenzepine, 10.7 +/- 1.8 nmol/kg/h for 4-DAMP and 19.4 +/- 5.2 nmol/kg/h for atropine. A similar sequence in the inhibitory potency was observed in 2-deoxy-D-glucose (2-DG, 100 mg/kg)-stimulated PP release, exocrine pancreatic, and gastric secretions. On the other hand, loxiglumide, a CCK receptor antagonist, did not influence PP release stimulated by 2-DG. These findings suggest that both CCK- and 2-DG-stimulated PP releases are mainly under cholinergic nerve control mediated by M3 muscarinic receptor in dogs.
Animals↗
[Early detection of pancreatic cancer by serum markers].
Serum markers such as pancreatic enzymes and tumor markers are useful for the diagnosis of pancreatic cancer. Among 40 cases of pancreatic cancer, elevated values were observed for immunoreactive elastase (IRE) in 70% and for CA19-9 in 73%. Elevated serum IRE was observed more frequently in head cancer and resectable cancer, whereas elevation in CA19-9 occurred more often in body-tail cancer and unresectable cancer. Elevation of serum IRE and CA19-9 are useful for diagnosis of pancreatic cancer but it is not specific for pancreatic cancer. Therefore, we studied the clinical usefulness of a combination assay of various serum markers such as CA19-9, lipase, serum iron, amylase, albumin globulin ratio, tissue polypeptide antigen, immunoreactive trypsin, and CA125 using the logistic regression analysis. This assay showed higher sensitivity and high specificity for pancreatic cancer than CA19-9. This combination assay may be very useful for the diagnosis of pancreatic cancer.
Amylases↗
Current status of pancreatic stone protein.
Pancreatic stone protein (PSP) has been argued to play a crucial role in intraductal pancreatic stone formation in chronic pancreatitis. PSP was initially reported to inhibit calcium carbonate precipitation from human pancreatic juice and to be decreased in pancreatic secretions from patients with chronic pancreatitis. Recent clinical investigations have further demonstrated elevation of PSP in the serum and urine of patients with renal disease as well as pancreatic disease. However, the PSP reduction in pancreatic secretion in chronic pancreatitis remains controversial. Therefore, we review the current concept of PSP.
Calcium-Binding Proteins↗
Absence of linkage disequilibrium at amyloid precursor protein gene locus in Japanese familial Alzheimer's disease with 717Val-->Ile mutation.
To date, eleven independent FAD pedigrees with the 717Val-->Ile mutation have been identified. Interestingly, five pedigrees were of Japanese origin and four were of British origin. The apparent ethnic prediction of this mutation raises the possibility that there is a founder effect in these two island nations. We did not observe any significant linkage disequilibrium in any locus of APP and GT12 loci in the five Japanese FAD pedigrees with the 717Val-->Ile mutation. A founder effect would probably not be present in Japanese FAD pedgrees with the 717Val-->Ile mutation.
Alleles↗
Solution structure of pituitary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy.
The solution structures of the recently discovered neuropeptides PACAP38 and PACAP27 have been investigated in aqueous solution containing varying amounts of trifluoroethanol (TFE) by circular dichroism (CD) spectroscopy and a combination of 2D 1H nuclear magnetic resonance (NMR) spectroscopy, distance geometry, and refined molecular dynamics and energy minimization calculations. In aqueous solution both peptides show only small transitory amounts of stable structure while in 50% TFE they adopt ordered structures. Qualitative NOE data and the use of the chemical shift index of the alpha-protons identified the positions of alpha-helical regions. A set of low-energy conformations compatible with the quantitative NOE data were obtained for both and each set were subjected to RMS analysis to determine the positions of the secondary structure elements. PACAP38 has an initial disordered N-terminal domain of eight amino acids, followed by an alpha-helical structure stretching from Ser-9 to Val-26, which contains a discontinuity between Lys-20 and Lys-21, and in the C-terminal region there is a short alpha-helix between Gly-28 and Arg-34. The structure of PACAP27 mirrors remarkably closely that of PACAP38 and shows no fraying of the C-terminal helix. The physiological significance of the three structural domains (1-8, 9-26, and 27-38) of PACAP38 is shown by a comprehensive review of recent in vitro and in vivo investigations of PACAP analogues. The correspondence of the global structural features of PACAP with other members of this family of peptides (namely, secretin, glucagon, GHRF1-29 and VIP) is demonstrated by inspection of the chemical shift indices of the alpha-protons.
Amino Acid Sequence↗
[Three-dimensional MR angiography of the celiac artery with single breath holding].
We performed a three-dimensional MR angiography of the celiac artery with single breath holding. The measuring time was just twenty-three seconds. In four healthy volunteers, celiac arteries were visualized clearly, moved cephalad with expiration and caudad with inspiration. In two patients with the median arcuate ligament compression of the celiac artery, the degree of stenosis increased with deep expiration and decreased with deep inspiration. Using this technique, we obtained different vascular images with each respiratory phase. This technique is considered to be a useful three-dimensional MR angiography in the abdominal region without respiratory artifacts.
Celiac Artery↗
Longitudinal changes of plasma pancreatic enzymes and hormones in experimental pancreatolithiasis in dogs.
Plasma pancreatic enzymes and hormones were longitudinally observed after producing partial obstruction of the major pancreatic duct in dogs to study an initial state of chronic pancreatitis or pancreatolithiasis. Fasting plasma immunoreactive cationic trypsin was elevated during the first six months and then decreased in a subgroup with pancreatic calculi, marked fibrosis, or duct dilatation when compared with the corresponding opposite at the end of the 12-month period. Similar but less prominent changes were found in fasting plasma immunoreactive pancreatic polypeptide (IRPP). Plasma amylase, glucose, or immunoreactive insulin or glucagon (IRG) show no significant variation. Plasma IRG and IRPP responses to intravenous insulin were reduced in the subgroups with marked pancreatic changes towards the end of the 12-month period. These results suggest that plasma pancreatic enzymes and hormones remain elevated as long as pancreatic damage is mild and then start to decline as the damage progresses in chronic pancreatitis or pancreatolithiasis.
Amylases↗
The inhibitory effect of octreotide on exocrine pancreatic secretion in conscious dogs.
The effects of somatostatin and its analogue, octreotide (SMS201-995), on pancreatic secretion and gastroduodenal motility in response to secretin and cholecystokinin octapeptide (CCK-8) were studied in five conscious dogs. Intravenous infusions of octreotide or somatostatin (1 nmol kg-1 h-1) inhibited periodic pancreatic secretion and the potentiation of fluid and bicarbonate responses to secretin at 60 ng kg-1 h-1 associated with the interdigestive gastroduodenal motility peaks (migrating motor complex). Pancreatic fluid and bicarbonate responses to secretin (125-1,000 ng kg-1 h-1) were not inhibited by octreotide or somatostatin. Pancreatic protein and enzyme responses to secretin and CCK-8 at 50 and 100, but not at 200 and 400, ng kg-1 h-1 were inhibited by octreotide and somatostatin. These inhibitory effects were similar to those of atropine (25 micrograms kg-1 h-1). The inhibition of protein responses to CCK-8 (100 ng kg-1 h-1) was dependent on octreotide dose. It is concluded that both octreotide and somatostatin, like atropine, inhibit interdigestive pancreatic secretion and the responses to small, but not large, doses of secretin and CCK-8 in conscious dogs.
Animals↗
A missense mutation at codon 105 with codon 129 polymorphism of the prion protein gene in a new variant of Gerstmann-Sträussler-Scheinker disease.
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Base Sequence↗
[Mutation analysis of amyloid precursor protein in early-onset familial Alzheimer's disease].
Recently, three different mutations have been found at codon 717 of the amyloid precursor protein (APP) gene, changing the native valine to isoleucine, phenylalanine and glycine in some familial Alzheimer's disease (FAD) kindreds. More recently, some other mutations have also been reported at codons 670 and 671 (double mutation), and codon 692. As analysis of coding region except exon 16 and 17 has been insufficient in previous reports, we analyzed entire coding region of the APP gene of 6 Japanese early-onset FAD kindreds using automated sequencer. Three FAD families showed known 717 Val to Ile mutation, whereas no novel mutations were detected.
Age of Onset↗
[Absence of linkage disequilibrium at amyloid precursor protein gene locus in Japanese familial Alzheimer's disease with 717Val-->Ile mutation].
To date, eleven independent early onset familial Alzheimer's disease (EOFAD) pedigrees with the 717Val-->Ile mutation of amyloid precursor protein (APP) gene have been identified. Interestingly, five pedigrees have been of Japanese origin. The apparent ethnic prediction of this mutation raises the possibility that there is a founder effect in Japan. If the hypothesis holds true, we can expect the presence of linkage disequilibrium at the APP locus. We did not, however, observe any significant linkage disequilibrium at any locus of APP or the adjacent GT12 locus in the five Japanese EOFAD probands with the 717Val-->Ile mutation. The result indicates that a founder effect would probably not be present in Japanese EOFAD pedigrees with the 717Val-->Ile mutation.
Age of Onset↗
Vasodilator action of guinea pig vasoactive intestinal polypeptide (VIP): comparison with common mammalian VIP.
The vascular activity of guinea pig (gp) and common mammalian (p) VIP were compared in anesthetized guinea pigs and dogs. In the guinea pig, intravenous injections of gpVIP and pVIP increased pancreatic blood flow and reduced the systemic arterial pressure and pancreatic vascular resistance in a dose-related manner. There were no significant differences in the vasodilator actions of these two VIPs, indicating that the overall cardiovascular actions of gpVIP and pVIP are similar in guinea pigs. In the dog, gpVIP, when given intra-arterially, was less potent (about 1/4) than pVIP in its action on femoral blood flow, suggesting that the blood vessels of the dog hind leg are more sensitive to its own VIP than to gpVIP. Oxidation of pVIP and gpVIP with H2O2 greatly reduced their vasodilator effects on the femoral arterial blood flow. The vascular effects were restored to control levels by reduction of the oxidized peptides with mercaptoethanol, which suggests that methionine residues of gpVIP and pVIP are important in the vasodilator effect on the femoral arterial bed in dogs.
Animals↗
Coenzyme Q10, iron, and vitamin B6 in genetically-confirmed Alzheimer's disease.
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Alzheimer Disease↗
[Evaluation of multislice dynamic MR imaging of the whole liver by inversion recovery snap shot FLASH method].
We acquired dynamic images over the whole liver by inversion recovery snap shot FLASH method after a bolus intravenous injection of Gadolinium-DTPA. Each nodule of hepatoma in the liver showed early enhancement and gradually turned to show low intensity. In two cases of hepatoma, small intrahepatic metastases, which were not detected by US, CT and spin-echo image of MRI, were suspected as high intensity nodules on early phase. Also recurrent areas after TAE were enhanced on early phase. This method is practical for improving the detection of lesions and is useful for evaluating the recurrence after TAE.
Carcinoma, Hepatocellular↗
[Multi-directional stereo viewing of MR angiography].
A new method was developed to display MR angiographic images. Nine MR angiographic images rotated along the cranio-caudal axis with ten incremental degree were constructed. These images were printed from left-anterior-oblique view to give a stereoscopic effect. With the stereoscopic viewing of these images, multiple stereoscopic images with different viewing directions were observed at once. Anatomical relationships of the vessels were more clearly understood than usual stereoscopic viewing. This multi-directional stereo viewing method is useful to display not only the MR angiographic images but also other multi-viewing techniques.
Blood Vessels↗