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Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 757 records · Page 42Linked to original sources

Plasma endothelin levels during myocardial ischemia and reperfusion.

Endothelin, an endothelium-derived vasoconstrictive peptide, has a strong potency of coronary artery constriction. However, the role of endogeneous endothelin under pathophysiological conditions has not yet been known. In this study, we examined plasma endothelin concentration in dogs with myocardial ischemia and reperfusion. Anesthetized open-chest dogs underwent either 45 minutes occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion, or 4-10 hours of continuous occlusion. Plasma concentration of endothelin from the central vein was measured by the highly sensitive enzyme-immunoassay. Plasma endothelin concentration increased 2.2-fold with the peak level at 60 minutes after release of the ligated artery, but occlusion per se caused no remarkable change. These data suggest that reperfusion of the occluded artery might be needed to increase the plasma concentration of endothelin in case of myocardial infarction.

Animals↗

Motor potentials evoked by magnetic stimulation of the motor cortex in normal subjects and patients with motor disorders.

Motor evoked potentials (MEPs) elicited by magnetic coil stimulation of motor cortex were studied at rest and during maximum voluntary muscle contraction in 20 normal subjects and 42 patients with motor disorders. MEP parameters employed in this study included: onset latency, amplitude, MEP/M wave amplitude ratio and background EMG/MEP area ratio. Maximum voluntary contraction increased the amplitude of MEPs compared to the size of M waves elicited by peripheral nerve stimulation. A reduced MEP/M wave amplitude ratio had a higher correlation with pyramidal tract involvement than did a prolonged MEP onset latency. Analysis of MEP parameters may help in the differential diagnosis of cerebral infarction, ALS and cervical spondylotic radiculomyelopathy. The inhibitory period which follows MEPs during voluntary contraction was observed in all subjects; the mean duration in normal subjects was 126.6 +/- 29.5 msec. The mean duration of the inhibitory period in patients with cerebral infarction, ALS and cervical spondylotic radiculomyelopathy was 73.9 +/- 41.7 msec, 79.5 +/- 54.5 msec and 85.1 +/- 36.5 msec, respectively. These values were significantly shorter than in normal subjects.

Adult↗

Two-dimensional computer color graphics of gastric mucosal blood distribution in normal subjects and ulcer patients.

The mucosal blood volume in 20 to 24 different regions of stomach was estimated by reflectance spectrophotometry during endoscopy, and an image showing mucosal blood distribution was made by two-dimensional computer color graphics with the aid of a personal computer. In 55 normal controls, the estimated mucosal blood volume (EMBV) was greater in the corpus mucosa than in the antral mucosa, and less in the lesser curvature than in the greater curvature. The volume in the anterior and posterior walls was almost the same. In 15 patients with active gastric ulcers in the angular region, the EMBV was decreased in all regions in the stomach. In 37 patients with healing ulcers, the EMBV increased, resuming the same levels as in normal controls. However, the EMBV around the ulcer increased remarkably at this stage. In 35 patients with ulcers in the scarring stage, the distribution of the EMBV was similar to that in the normal controls. These hemodynamic changes were shown clearly in a color display with the aid of a personal computer. This method could offer new possibilities in endoscopic research.

Adult↗

Analysis of mucosal blood hemoglobin distribution in gastric ulcers by computerized color display on electronic endoscopy.

A technique of computerized color display was used to analyze the mucosal blood hemoglobin distribution in patients with gastric ulcers. Using an electronic endoscope, red and green images (Vr and Vg) obtained separately from the electronic endoscopic image were transferred to an image analyzer and a computer. The mucosal hemoglobin content was calculated at each pixel of the image using the formula: index of hemoglobin content = 32[log2(Vr/Vg)]. Forty endoscopy examinations were performed in 15 patients with small ulcers (less than or equal to 1 cm) in the gastric angle and 5 normal subjects. The index of hemoglobin content ranged from 24 to 40 in the normal subjects. The index for the area around an active ulcer was mostly below 33. In cases of ulcers in the healing stage it increased to more than 40. The index was still above 40 in ulcer scars in the S1 stage, but within normal range in most of the mucosa in the S2 stage. Thus, the mucosal blood hemoglobin distribution can be assessed by computerized color analysis in patients with gastric ulcers at various stages.

Data Display↗

Sialyl cholesterol is translocated into cell nuclei and it promotes neurite outgrowth in a mouse neuroblastoma cell line.

To determine the mechanisms of the neuritogenesis induced by synthetic sialyl cholesterol (SC) in a mouse neuroblastoma cell line, Neuro2a, the biochemical fate of SC and ganglioside GM1 (IV3NeuAc-GgOse4Cer) was investigated. The kinetics of incorporation of SC and GM1 into cells for the two compounds were similar. SC was not degraded nor modified for at least 24 h after the incorporation, indicating that SC itself and not its metabolites were responsible for the neuritogenic activity. Cell fractionation experiments showed that approximately 40% of the incorporated SC was localized in the nucleus, 25% in the plasma membrane fractions, and 11-14% in the granule fraction. This distribution was different from that of GM1. The nuclear SC was found to affect de novo RNA synthesis, indicating its biological effect may be mediated at the level of transcription. SC also increased the rates of both Ca2+ influx and efflux, although the intracellular level of total Ca2+ remained unchanged. Levels of inositol 1,4,5-triphosphate (IP3) also remained unchanged and the SC dependent neuritogenesis was not inhibited by an excess amount of W-7, an inhibitor of Ca2+/CaM kinases. These results again accord with the suggestion that SC and GM1 do not utilize Ca2+, IP3 or Ca2+/CaM as a second messenger for neuritogenesis. Rather it appears very likely that the nuclear localized SC may play a key role in neuritogenesis.

Animals↗

Isolation and characterization of major urinary oligosaccharides excreted by a patient with type 3 GM1 gangliosidosis.

Two major oligosaccharides were isolated from the urine of a patient with type 3 GM1 gangliosidosis. From structural studies including compositional sugar analysis, fast-atom bombardment mass spectrometry, direct-inlet chemical ionization mass spectrometry, methylation analysis, chromium trioxide oxidation, and proton magnetic resonance spectroscopy, their structures were deduced to be as follows: [formula: see text] Both oligosaccharides have beta-linked galactose at the non-reducing ends. Oligosaccharide 1 is one of the most common urinary oligosaccharides found in type 1 and type 2 GM1 gangliosidosis. Oligosaccharide 2, lacto-N-difucohexaose II, has not been described in the urine of GM1 gangliosidosis patients. Excretion of oligosaccharide 1 in the type 3 patient was much less than that of a type 2 patient. Thin-layer chromatographic analysis revealed that the excretion of oligosaccharides with higher molecular weight than that of oligosaccharide 1 (octasaccharide) in the type 3 patient was much less than that of a type 2 patient, raising the possibility that the mutant beta-galactosidase of type 3 GM1 gangliosidosis can still act to some extent on higher molecular weight oligosaccharides containing beta-linked galactose at the non-reducing end.

Carbohydrate Conformation↗

Phase I study on human monoclonal antibody against cytomegalovirus: pharmacokinetics and immunogenicity.

MAb C23, a human immunoglobulin G1 (IgG1) monoclonal antibody (MAb) against cytomegalovirus, was administered to 20 healthy volunteers. Sixteen of them received a single infusion of a dose ranging from 5 to 80 mg. The plasma clearance curves fit a two-compartment model, with half-lives of 31.0 +/- 23.6 h in the diffusion phase and 24.2 +/- 5.8 days in the equilibration phase. The plasma after administration had the virus neutralization activities that were equivalent to the plasma MAb C23 levels. The remaining four subjects, who received three infusions of 60, 20, and 20 mg at 1-week intervals, showed pharmacokinetics that were very consistent with those of the single infusion. No antibody response against MAb C23 was observed in any of the subjects at any time, when monitored for approximately 60 days after the single infusion or the third infusion of the three repeated doses. None of the 20 subjects showed any treatment-related clinical signs or changes. These results suggest that a human IgG MAb has the same pharmacokinetic characteristics as those of natural human serum IgG, and that it is not immunogenetic and is safe in humans.

Antibodies, Anti-Idiotypic↗

SPECT evaluation of brain perfusion reserve by the acetazolamide test using Tc-99m HMPAO.

This report describes a new approach to the evaluation of brain perfusion reserve using Tc-99m HMPAO SPECT. Consecutive brain Tc-99m HMPAO SPECT studies before and after acetazolamide (Diamox) administration were performed within 30 minutes on 19 patients with significant vascular occlusive lesions. Thirteen patients showed decreased perfusion reserve and four patients maintained perfusion reserve in the affected vascular territories after Diamox administration, providing additional information to baseline Tc-99m HMPAO SPECT in 17 (89%) patients. Although flow augmentation post-Diamox was underestimated, possibly due to the nonproportionality of Tc-99m HMPAO activity to true blood flow, significant changes in the brain perfusion pattern were both visually and quantitatively determined using an image subtraction technique. This consecutive Tc-99m HMPAO SPECT technique seems to be of practical use for the evaluation of brain perfusion reserve and for the improvement of the sensitivity of detecting pathologic areas.

Acetazolamide↗

Two Japanese cases with aspartylglycosaminuria: clinical and morphological features.

Two members of a consanguineous Japanese family with a clinical picture of aspartylglycosaminuria (AGU) are described. Both patients exhibited mental retardation, coarse facial features, angiokeratoma and myoclonic seizures. Biochemical studies showed elevated excretion of urinary sialyloligosaccharides and decreased activity of aspartylglycosaminidase in lymphoblasts. Morphologic studies of skin biopsy specimens showed many clear vacuoles mainly in the vascular endothelial cells and secretory cells of the sweat glands. Osmiophilic lamellar cytoplasmic inclusions were also noted in the ganglion cells in rectal biopsy. The ethnic distribution of AGU may be more widespread than previously suspected and appears not to be restricted to Finnish populations. Ours are the first Japanese patients diagnosed as AGU. We conclude that AGU should also be included in the differential diagnosis of mentally retarded patients in Asian countries.

Acetylglucosamine↗

Multiple neurite formation in neuroblastoma cell lines by griseolic acid, a potent inhibitor of cyclic nucleotide phosphodiesterases.

The morphological change of several neuroblastoma cell lines induced by griseolic acid, a novel and potent inhibitor of cyclic nucleotide phosphodiesterase (PDE), was examined. In the cell lines tested, Neuro-2a (a murine neuroblastoma cell line) showed dose-dependent (1 microM-1 mM) neurite extension. Griseolic acid markedly increased the intracellular cyclic AMP level of Neuro-2a cells, suppressed DNA synthesis (82% at 1 mM), and induced multipolar (multiple-neurite-bearing)-type neuritogenesis. A similar type of neurite outgrowth was induced by 8-bromo-cyclic AMP, which also elevated the intracellular cyclic AMP concentration. In contrast, when Neuro-2a cells were treated with retinoic acid, neurite formation was of the monopolar (single-neurite-bearing) type. Papaverine and theophylline, which have been frequently used as PDE inhibitors, failed to induce these morphological changes up to 1 mM, probably owing to the lesser potency of these compounds as compared with griseolic acid on the inhibition of PDE. Retinoic acid, theophylline, and papaverine were ineffective at elevating the intracellular cyclic AMP level. These results suggest that multipolar-type cell shape change in Neuro-2a cells is correlated with the accumulation of intracellular cyclic AMP and that griseolic acid is a useful compound to induce neuroblastoma cells into terminal differentiation.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Adult-form galactosialidosis: ocular findings in three cases.

We reported ocular findings of 3 patients with adult-form galactosialidosis. Diffuse fine opacities in the deep layer of the corneal stroma, an obscure cherry-red spot of the macula and optic nerve atrophy were noted in all cases. Punctate lenticular opacities were observed in 2 cases. Slowly progressive visual disturbance was seen in all cases, and it might be due to secondary optic nerve atrophy caused by retinal ganglion cell death.

Adult↗

Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis.

We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis. To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions. Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated. Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients. Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls. The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome.

Adult↗

Simple detection of tRNA(Lys) mutation in myoclonus epilepsy associated with ragged-red fibers (MERRF) by polymerase chain reaction with a mismatched primer.

We developed a simple method for the detection of a tRNA(Lys) mutation in myoclonus epilepsy associated with ragged-red fibers (MERRF) by polymerase chain reaction with use of a mismatched primer. Although the tRNA(Lys) mutation does not alter recognition sequences for commercially available restriction enzymes, we have successfully changed two nucleotides flanking the A to G mutation at nucleotide position 8344 in a tRNA(Lys) gene of a mitochondrial genome. As a result, the mutation can be detected as a Nae I restriction fragment length polymorphism. With this method, all eight MERRF patients and an asymptomatic mother of a MERRF patient, from six independent families, had the same tRNA(Lys) mutation. Our method is simple and should also be useful for the quantitation of heteroplasmies.

Base Sequence↗

Linkage analysis of juvenile parkinsonism to tyrosine hydroxylase gene locus on chromosome 11.

We performed linkage analyses of juvenile parkinsonism with autosomal recessive inheritance (AR-JP) to chromosome 11p15.5 locus including tyrosine hydroxylase (TH), Harvey-ras-1 (HRAS), and insulin (INS) genes by analyzing genomic DNA from 28 members of seven Japanese AR-JP families containing 10 affected individuals. We used the methods of pairwise linkage analysis (LIPED) and multipoint linkage analysis (LINKAGE) for genetic linkage to the chromosome 11p15.5 markers and detected recombination events between AR-JP locus and TH gene. Multipoint linkage analysis excluded the linkage in the interval between TH and HRAS, as well as 11 cMo distal to TH and 8.5 cMo distal to HRAS, a total of approximately 23 cMo on chromosome 11p.

Adolescent↗

Percutaneous absorption of bromhexine in rats.

The percutaneous absorption of bromhexine (BH), an expectorant drug, through rat skin was examined in vitro and in vivo. BH in free base form penetrated better than the hydrochloride through the skin. When the in vitro penetration of BH was compared using Plastibase, macrogol and sucrose ester of fatty acid F-160 (DK-ester) formulations, the DK-ester formulation showed the best penetration of BH of the three. The addition of Azone (3%) or lauric acid (BH: lauric acid molar ratio, 1:1) considerably increased BH penetration to a relatively large penetration rate. The plasma levels of BH after in vivo application of the DK-ester formulation with Azone or lauric acid (0.6 g/3.8 cm2) were also higher than those after the formulation without an enhancer, and a constant plasma level (20-50 ng/ml) was obtained during the application for 48 h. However, the bioavailability was low, 2.5 and 2.7% respectively. When the amount of BH remaining in DK-ester ointment and the skin after an 18-h application was measured, the BH content in the ointment was 88.6 +/- 8.0% for the formulation without Azone and 93.7 +/- 6.9% for that with Azone. The low penetration and low bioavailability observed will thus be due to the high drug retention of the base.

Animals↗

Incomplete protection mechanism against vesico-ureteral reflux and hydronephrosis in the inbred mouse strain DDD.

We have previously reported the occurrence and inheritance mode of hydronephrosis in the inbred mouse strain DDD. The present investigation examined the possibility that hydronephrosis may be caused by a vesico-ureteral reflux (VUR). Bladder pressure was measured under anaesthesia in 3 strains of mice (DDD, ddY and C57BL/6). VUR was demonstrated by lower bladder pressure only in the DDD strain. Loading pressure into the renal pelvis (LPP) was significantly higher in DDD than in C57BL/6 (P less than 0.001). Correlations between LPP and severity of hydronephrosis were significantly positive in DDD and ddY, indicating that mice showing higher LPPs had the severest disease. Scanning electron micrography revealed that the ureteral orifice of DDD (100-300 microns) was much larger than in C57BL/6 (30 microns), and thus offered scant protection against VUR in DDD. These results suggest that DDD hydronephrosis caused by VUR is related primarily to the absence of an adequate protection mechanism in the ureteral orifice.

Animals↗

Age-related change in human gastric mucosal energy metabolism.

Many investigators have reported a decrease in mucosal blood flow resulting in impairment of gastric mucosal energy metabolism in animal experiments. Recently, endoscopic studies using reflectance spectrophotometry and laser Doppler flowmetry have indicated that gastric mucosal blood flow in humans decreases with age. However, changes in energy metabolism in human gastric mucosa with age remains obscure. In this study, we measured adenine nucleotides in biopsy samples from human gastric mucosa, using high-performance liquid chromatography, and investigated changes in energy metabolism with age in subjects proven normal endoscopically. Energy charge (EC = (ATP + 1/2 ADP)/ATP + ADP + AMP) in the gastric antral and body mucosa showed decrease with age. When the subjects were divided into two groups, less than and more than 65 years old, the EC level was significantly lower in the latter than the former in both antral and body mucosa (0.65 +/- 0.06 versus 0.74 +/- 0.03 in the antrum, 0.73 +/- 0.04 versus 0.79 +/- 0.04 in the body) and significantly less in the antral mucosa than in body mucosa in both groups. The adenosine triphosphate (ATP) level in the older group showed a significant decrease (6.48 +/- 1.14 versus 9.63 +/- 1.92 in the antrum, 8.59 +/- 1.64 versus 10.60 +/- 2.13 in the body) compared with those less than 65 years old. In the antral mucosa of the older group the adenosine diphosphate (ADP) level was also significantly lower than that in the group less than 65. In conclusion, in the elderly, the energy metabolism in human gastric mucosa is impaired, and this may weaken their defensive mechanism.

Adenine Nucleotides↗