Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 541 records · Page 30Linked to original sources

PubMed1995

Sympathetic skin responses evoked by magnetic stimulation of the neck.

We studied sympathetic skin responses (SSRs) following magnetic stimulation of the neck in 40 normal subjects and 54 patients with neurological diseases and active sweat gland densities (ASGDs) at the foot induced by pilocarpine in 39 patients. SSRs at the hand following magnetic stimulation showed the lowest coefficients of variability of the latencies and amplitudes in eight consecutive responses compared with SSRs following other types of stimuli (electrical and auditory stimulation, and deep inspiration) in 12 normal subjects. Fourteen of 38 patients with neuropathies (37%) showed the presence of SSRs after magnetic stimulation, but not after median nerve stimulation, although SSRs to magnetic stimulation corresponded with those to nerve stimulation in all patients with multiple sclerosis or multiple system atrophy. These results suggest that the absence of SSRs after nerve stimulation in patients with neuropathies may be due to abnormalities of the peripheral sensory afferent fibers. ASGDs significantly correlated with SSRs at the foot following magnetic stimulation, but not with those following nerve stimulation in patients with neuropathies. Magnetic stimulation of the neck is the highly reproducible method of evoking SSRs because this technique is able to produce strong sensory afferent inputs proximally. Furthermore, SSRs following magnetic stimulation, little influenced by sensory afferent fiber involvement, are very useful for evaluating the postganglionic sympathetic function in patients with neuropathies.

Action Potentials↗

PubMed1995

Low intensity areas observed on T2-weighted magnetic resonance imaging of the cerebral cortex in various neurological diseases.

The cerebral cortex of patients with Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS) may show low signal intensity on T2-weighted magnetic resonance images (MRI). Since these low intensity areas (LIA) are also often observed in aged patients with other diseases, we suspected that they might be a non-specific finding. We conducted a retrospective study of LIA in 139 patients with various diseases of the central and peripheral nervous systems, and evaluated their relationship to age and other MRI findings. Brain atrophy, ventricular dilatation, white matter lesions, and LIA were visually evaluated on axial images of the spin echo sequences obtained with a 1.5 tesla (T) system. We found that LIA appeared after age 50 and became more common with advancing age. Their presence correlated with brain atrophy and white matter lesions. They were most frequent in the motor cortex, followed by the occipital and sensory cortices. Their incidence in the motor cortex was significantly higher in patients with central nervous system diseases than in those with peripheral neuropathy. We conclude that LIA are common in old patients with various neurological diseases and suggest that the deposition of iron in the cerebral cortices causes their development.

Adolescent↗

PubMed1995

Effect of sleep stage on somatosensory evoked potentials by median nerve stimulation.

The effects of sleep stage on early cortical somatosensory evoked potentials (SEPs) and short-latency components elicited by median nerve stimulation were studied in 12 normal volunteers. The latency of P13 in the awake stage was not significantly different from that in any sleep stage. The latencies of N16, N20 and P20 were significantly prolonged while the amplitude of N20 was decreased during the non-rapid eye movement (NREM) sleep stage. P22, P23 and N24 components showed double peaks (P23a, P23b, N24a, N24b) during the NREM sleep stage in 6 subjects, while N24 showed a single peak and only P22 and P23 showed double peaks in 5 other subjects. The latencies and morphologies of SEPs during rapid eye movement sleep stage were almost the same as those during the awake stage. These findings suggest that NREM sleep affects the latency, amplitude and morphology of N16 and early cortical components.

Adolescent↗

PubMed1995

Changes in growth inhibitory factor mRNA expression compared with those in c-jun mRNA expression following facial nerve transection.

We investigated growth inhibitory factor (GIF) mRNA expression within the rat facial nucleus with the aid of in situ hybridization. We found that GIF mRNA was expressed abundantly in the facial motoneurons of sham operated animals, and that this gene expression decreased after transection of the facial nerve. This decrease of GIF mRNA was first detected on the third day and was maintained for at least five weeks after transection of the nerve. Changes in c-jun, an immediate early gene, were also investigated with this model, and it was found that c-jun mRNA started to increase in the facial nucleus on the first day and that this increase was maintained for at least 5 weeks. These results suggest that the facial motoneurons, when their axons are transected, continuously respond to the injury and that GIF mRNA is actively suppressed to reduce the inhibition of neurite outgrowth in order to regenerate the axons.

Animals↗

PubMed1995

Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 1. Mouse strains bearing different MHC molecules produce antibodies on immunization with recombinant Yo protein, but do not cause Purkinje cell loss.

Passive transfer of anti-Yo antibody from patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecological or breast carcinoma has not been successful in inducing an animal model. We used active immunization with recombinant Yo protein of four strains of mice bearing different MHC molecules: BALB/c (H-2d), C3H (H-2k), C57BL/6 (H-2b), SJL/J (H-2s). All the strains produced high anti-Yo antibody titer but none developed cerebellar ataxia or showed Purkinje cell loss. Spleen cells from the immunized mice also reacted with recombinant protein. Because C57BL/6(nu/nu) mice produce no anti-Yo antibody, mature helper T cells are required for its production. Results suggest that antibody production in peripheral blood alone is not sufficient for the development of PCD and that MHC class II molecules function in the activation of T cells to help B cells to help B cells produce antibodies.

Animals↗

PubMed1995

Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice.

Passive transfer of serum IgG or mononuclear cells from peripheral blood of a patient with paraneoplastic cerebellar degeneration (PCD) to rodents was carried out in order to examine the role of anti-Purkinje cell antibody (anti-Yo antibody) present in serum and cerebrospinal fluid of PCD patients. After a single injection of IgG into mouse brain, it was taken up by Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells into rat ventricles did not cause Purkinje cell loss. We also studied passive transfer of the PCD patient's lymphocytes to mice with severe combined immunodeficiency (SCID). We constructed a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody for immunizing mice, and that resulted in production of significant amounts of anti-Yo antibody. Spleen cells from these Yo protein immunized mice were injected intravenously or intracerebrally into naive mice that subsequently showed no neurological symptoms or loss of Purkinje cells. We conclude that the anti-Yo antibody, either in combination with or without complement or activated mononuclear cells, cannot be the sole cause of Purkinje cell loss.

Adenocarcinoma↗

PubMed1995

Shear stress-induced platelet aggregation in various types of von Willebrand disease.

We here examined the shear stress-induced platelet aggregation (SIPA) in various types of von Willebrand Disease (vWD), using a novel cone-and-plate viscometer recently developed by Ikeda et al. [1]. Under experimental conditions of high shear stress (90-108 dyne/cm2) known to induce von Willebrand factor (vWF)-dependent platelet aggregation in normal individuals, a variety of SIPA patterns, from a normal to total defect, were observed in 6 patients with type I vWD, while SIPA was totally absent in all 7 type IIA patients examined. One patient with Normandy type vWD exhibited a normal SIPA pattern under these experimental conditions. These findings, together with the vWF parameters of each patient, suggested that the presence of higher molecular weight multimers of plasma vWF, as well as an appropriate level of vWF antigen, is essential for SIPA to occur under high shear stress. Interestingly, vWF-dependent SIPA in 3 patients with type IIB vWD was found to be initiated by a low shear stress force, which did not induce such platelet aggregation in normal individuals. This might explain the intravessel platelet clumping that occurs, resulting in the intermittent thrombocytopenia observed in this type of the disease.

Adolescent↗

PubMed1995

The 8,344 mutation in mitochondrial DNA: a comparison between the proportion of mutant DNA and clinico-pathologic findings.

Ten patients, two men and eight women with mitochondrial encephalomyopathy, had an A-G mutation at nucleotide pair 8,344 in the mitochondrial DNA, the most common genetic defect in myoclonus epilepsy with ragged-red fibers (MERRF). Eight patients had the clinical and pathologic characteristics of MERRF including myoclonus, seizures, cerebellar ataxia and myopathy with ragged-red fibers. Two patients had atypical symptoms such as early onset of fatal cardiac failure and late onset of rapid mental deterioration, respectively. The striking feature in our patients with the 8,344 mutation cardiac involvement and two developed progressive heart failure. In the typical MERRF patients, the proportion of mutant mitochondrial DNA in their skeletal muscles, quantified by a single strand conformation polymorphism analysis, was above 85%. However, there was no significant correlation between clinical severity, histopathological findings and the proportion of mutant mtDNA in muscle biopsy samples, suggesting that non-ragged-red fibers play an important role in the phenotype expression of the mutants.

Adolescent↗

PubMed1995

Synthesis of radioiodinated analogs of 2-(4-phenylpiperidino)cyclohexanol (vesamicol) as vesamicol-like agent.

Three iodovesamicol analogs, iodinated at the ortho, meta, and para positions of the 4-phenylpiperidine moiety, were synthesized and labeled with 125I by isotopic exchange reaction. Their potencies as a vesamicol-like drug were evaluated with competitive inhibition studies using (-)[3H]vesamicol. The radiochemical yields were 40-85%, the radiochemical purities exceeded 95% and their specific activities were 370-740 GBq/mmol. The descending order of binding affinity of the tested compounds against the vesamicol receptor was m-iodovesamicol > o-iodovesamicol > p-iodovesamicol. The receptor binding affinity of m-iodovesamicol (IC50 = 133 nM) was comparable with that of vesamicol (IC50 = 109 nM). Therefore, the meta position of the 4-phenylpiperidinyl fragment of vesamicol was the optimum site for iodination, and radioiodinated m-iodovesamicol may serve as a useful radiopharmaceutical for in vitro and in vivo studies of presynaptic cholinergic neurons in rats.

Animals↗

PubMed1995

In vivo characterization of radioiodinated 2-(4-phenylpiperidino)cyclohexanol (vesamicol) analogs: potential radioligand for mapping presynaptic cholinergic neurons.

Iodovesamicol analogs, radioiodinated at the ortho (1), meta(2) and para(3) positions of the 4-phenylpiperidine moiety, were evaluated as potential presynaptic cholinergic neuron mapping agents. Significant accumulation of m-[125I]iodovesamicol (mIV(2)) (about 3% of the injected dose) was noted in the rat brain with prolonged retention times. The accumulation of mIV(2) in the rat brain was decreased by 67% by 5 min pre-injection of dl-vesamicol(1 mumol/kg). Pre-injection of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperdine[(+)-3-PPP](0.75 mumol/kg) did not markedly decrease the levels of radiotracers (oIV(1) and mIV(2)) in the rat brain. These results suggest that radioidinated m-iodovesamicol (mIV(2)) is suitable for use in presynaptic cholinergic neuron mapping.

Animals↗

PubMed1995

Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy and dementia as well as various ages of onset. We have identified a specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 as the pathogenic mutation for DRPLA. We investigated how the degree of the expansion of the CAG repeat affects the clinical manifestations of DRPLA. The sizes of the expanded alleles were well correlated with the ages of onset (r = -0.6955, P < 0.001). Patients with progressive myoclonus epilepsy (PME) phenotype had larger expansions (62-79 repeats) and earlier ages of onset (onset before age 20). Furthermore, most of the patients with PME phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with non-PME phenotype showed later ages of onset (onset after age 20) and smaller expansions (54-67 repeats). When ages of onset of each clinical symptoms are compared with sizes of the CAG repeat, there is again a remarkably high correlation of the sizes of CAG repeat with each of the clinical symptoms. Thus the wide variation in clinical manifestations of DRPLA can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.

Adult↗

PubMed1995

Relation between grip strength and radial bone mineral density in young athletes.

In this study, we evaluated the relationship between bone mineral density (BMD) and muscle strength in young athletes who had not yet experienced age-related bone loss. Radial BMD and grip strength were measured in 10 male college wrestlers, 16 female college basketball players, and 12 female college tennis players. Radial BMD was measured in the distal and middle radius by dual energy x-ray absorptiometry (DEXA). Isometric grip strength was assessed with a hand-held dynamometer. The dominant forearm was examined in the amateur wrestlers and basketball players for grip strength and BMD. Both forearms were examined in the tennis players. A significant positive correlation was found between radial BMD and grip strength in the dominant forearm, and between radial BMD and body weight. Moreover, to eliminate a possible effect of body weight on radial BMD, we compared radial BMD with grip strength in both the dominant and nondominant arm of 12 college tennis players. Grip strength in the dominant forearm was significantly greater than in the nondominant forearm. The midradial BMD of the dominant forearm was also significantly higher than in the nondominant forearm. Based on these findings, we conclude that grip strength is one of the determinant factors of radial BMD in the dominant forearm of young college athletes.

Absorptiometry, Photon↗

PubMed1995

Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's disease.

A specific isoform of apolipoprotein E has been associated with the accelerated rate of disease expression of sporadic Alzheimer's disease (AD) and late-onset familial AD (FAD). An earlier age at onset has also been demonstrated in familial AD patients with mutations in the amyloid precursor protein (APP) gene (APP717 and APP670/671)13 carrying the APOE epsilon-4 allele compared to those who do not, but not in familial AD patients with APP692 or 693 mutations, or in chromosome 14-linked familial AD patients. Hypothesizing that receptors for apoE-containing lipoproteins act as a potential risk factor for AD, we performed an association study using a polymorphic triplet (CGG) repeat in the gene for the VLDL receptor (VLDL-R), a receptor for apoE-containing lipoproteins. The frequency of the 5-repeat allele was significantly higher in all of the Japanese sporadic AD patients (P < 0.02) than in the Japanese controls. Moreover, the odds ratio was significantly increased in the AD patients homozygous for the 5-repeat allele (OR = 2.1, 95% CI = [1.1-4.2]). Multiple logistic regression analysis reveals that the relative risk conferred by the presence of two copies of the 5-repeat allele and at least one copy of the APOE epsilon-4 allele is 8.7 (95% CI = [2.9-25.8]). Our results suggest that the VLDL-R gene is a susceptibility gene for AD.

Alleles↗

PubMed1995

Simultaneous analysis of mucosal and submucosal hemodynamics using infrared electronic endoscopy: effects of intraluminal acid on ulcer scars.

BACKGROUND AND STUDY AIMS: This report describes the use of an infrared electronic endoscope for the assessment of gastric mucosal and submucosal hemodynamics in ulcer scars. METHODS: The experimental ulcer scars were induced by acetic acid injection in five anesthetized dogs. Indices of mucosal hemoglobin content (IHb) and its oxygenation (ISO2) were calculated from reflectance spectra of the mucosa at 569, 577, 586, and 650 nm, which were obtained through an optic probe. The gastric submucosal vascular diameter was assessed by comparison with a reference wire under infrared endoscopic observation. RESULTS: The index of mucosal hemoglobin content measured by reflectance spectrophotometry was significantly higher at the ulcer scars than in the intact mucosa before the ulcer induction. Intraluminal administration of 0.2 N hydrochloric acid lowered IHb and ISO2 only at the ulcer scars. The diameters of the gastric submucosal veins beneath the ulcer scars decreased markedly after the acid administration. CONCLUSION: The results suggest abnormal responses of gastric mucosal and submucosal circulation at ulcer scars to intraluminal acid. Infrared electronic endoscopy is therefore a useful tool for the simultaneous analysis of mucosal and submucosal circulation in the stomach.

Animals↗

PubMed1995

Expression of growth inhibitory factor mRNA following cortical injury in rat.

Growth inhibitory factor (GIF) inhibits survival and neurite formation of cortical neurons in vitro and is found abundantly in the normal human brain. The role of GIF is still obscure, although it is reported to decrease in the brain in Alzheimer's disease. We examined changes in GIF mRNA expression in a rat cortical-ablation model with the aid of an in situ hybridization technique. In sham-operated animals, the GIF mRNA was expressed consistently in the cerebral cortex, hippocampus, and thalamus. One day after cortical ablation of the left somatosensory cortex, the expression tended to decrease in the cortex ipsilateral to the injury. Four days after surgery, it increased markedly in the affected cortex and thereafter returned to the level of the control animals except for the area surrounding the injury, where GIF mRNA again increased 2 to 3 weeks after ablation. The transient increase in GIF mRNA expression may reflect efforts to inhibit excessive sprouting of neurites. We also studied the effect of topically applied basic fibroblast growth factor (bFGF), which has a range of neurotrophic effects, on GIF mRNA expression. Topically applied bFGF enhanced the suppression of GIF at 1 day after surgery, though it did not affect the subsequent response. GIF can therefore be assumed to affect the outgrowth of injured neurites and might play a major role in maintenance of the neuronal network in cooperation with other trophic factors. Modification of these factors may be the key to improve neuronal damage after injury.

Animals↗

PubMed1995

Mechanism for ammonia-induced promotion of gastric carcinogenesis in rats.

Although an association is suggested between gastric cancer and prior infection with Helicobacter pylori (HP), the role of HP in gastric carcinogenesis remains obscure. HP has potent urease activity and produces ammonia, a factor causing HP-related gastroduodenal mucosal lesions. In this study, rats were examined in an effort to determine effects of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After pretreatment with MNNG (83 mg/l) for 24 weeks, a solution of either 0.01% ammonia or plain tap water was administered to the animals as drinking water for an additional 24 weeks. The administration of the 0.01% ammonia solution significantly increased the incidence and number of cancers in the glandular stomach. The numbers of cases in which these cancers penetrated the muscle layer or deeper and of low-grade differentiated adenocarcinomas were significantly higher in rats receiving the ammonia solution. Continuing administration of ammonia accelerated cell proliferation in the gastric mucosa, but had no effect on the serum gastrin level. Therefore, gastric ammonia, which stimulates mucosal cell proliferation, appears to be an important promoter in carcinogenesis in rats and possibly in the HP-related gastric carcinogenesis in humans.

Ammonia↗

PubMed1995

Molecular cloning and characterization of a third type of N-glycan alpha 2,8-sialyltransferase from mouse lung.

AcDNA encoding a new alpha2,8-sialyltransferase (ST8Sia IV), which exhibits activity toward the alpha,2,3-linked sialic acids of N-linked oligosaccharides, was cloned from a mouse lung cDNA library by means of the PCR-based approach. The predicted amino acid sequence of ST8Sia IV showed 15.2, 56.0, and 26% identity with those of so far cloned mouse alpha2,8-sialytransferases, i.e. GD3 synthase (ST8Sia I), STX(ST8Sia II), and Sia(alpha)2,3Galbeta1,4GlcNAc(alpha)2,8-sialyl-transferase (ST8Sia III). ST8Sia IV exhibits high amino acid sequence identity (99.2%) with recently cloned hamster polysialyltransferase-1 gene, which is necessary to polysialic acid expression, but no enzymatic activity of the gene product was reported [Eckhardt, M. et al. (1995) Nature 373, 715-718]. The ST8Sia IV gene was strongly expressed in lung, heart, and spleen, but only weak expression of the gene was observed in brain, without remarkable developmental regulation. The activity of mouse ST8Sia IV was specific toward sialylated glycoproteins. The linage-specific sialidase treatment of glycoproteins as well as N-linked oligosaccharides from the glycoproteins revealed that ST8Sia IV exhibits an alpha2,8-sialytransferase activity toward alpha2,3-linked sialic acids of N-linked oligosaccharides. ST8Sia IV can synthesize polysialic acid chain in vitro without any initiator sialytransferase.

Amino Acid Sequence↗

PubMed1995

Gastric ulcer healing and basic fibroblast growth factor: effects of lansoprazole and famotidine.

We examined the effects of lansoprazole and famotidine on gastric basic fibroblast growth factor (bFGF) levels and ulcer healing in patients with gastric ulcer. Sixteen patients with active gastric ulcer were divided into two groups and received treatment with lansoprazole 30 mg/day or famotidine 40 mg/day. They were examined endoscopically at 2, 4, and 8 weeks to measure gastric bFGF levels at the ulcer margin and to assess ulcer healing. Helicobacter pylori infection was determined by a rapid urease test. The two groups were comparable with regard to age, male:female ratio, H. pylori infection rates, and bFGF levels. During treatment, bFGF levels did not change significantly in the famotidine group, whereas they increased by a factor of 2.2 to 2.6 in the lansoprazole group. Cumulative healing rates were also significantly lower in the famotidine group than in the lansoprazole group. These results indicate that lansoprazole increases tissue bFGF levels and promotes gastric ulcer healing in humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗