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Biomedical subjects

S Ando

Publications and source records attributed to S Ando.

At least 109 records · Page 6Linked to original sources

Dentatorubropallidoluysian atrophy: clinicopathological study of dementia and involvement of the nucleus basalis of Meynert in seven autopsy cases.

This report concerns a clinicopathological study including a quantitative pathological study on the nucleus basalis of Meynert (nbM) of seven Japanese autopsy cases (four male, three female) of dentatorubropallidoluysian atrophy (DRPLA) with special reference to the clinicopathological correlation of dementia in DRPLA. In each case the pattern of the inheritance was consistent with that of an autosomal dominant trait. The neurological examination revealed that all seven individuals had cerebellar signs. Six patients had epilepsy and choreoathetoid involuntary movement; myoclonus was evident in five patients. Dementia was noted in all seven patients. Degeneration of the globus pallidus (particularly the lateral segment) and of the dentate nucleus was the principal pathological feature. Brain weights at autopsy ranged from 1020 to 1400 g (average 1241 g: male 1320 g, female 1135 g). The quantitative evaluation revealed no significant loss of neurons in the nbM as compared with a control group. There was no clinicopathological correlation between dementia and involvement of the nbM. We suggest that the dementia of DRPLA is due not to the involvement of the nbM, but to - as yet - unidentified pathology elsewhere.

Adolescent↗

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding.

Protein disulfide isomerase (PDI) is an enzyme that participates in the formation of disulfide bonds. It is also known to be the subunits of some enzymes and the membrane-associated thyroid hormone-binding protein. In this study, we measured the quantitative distribution of PDI protein in rat tissues and examined the relationship between protein level and enzyme activity in PDI during fasting and refeeding. Western blotting with specific anti-PDI antiserum detected the PDI protein band of 55 kd. Among several tissues, liver contained the largest amount of PDI protein, followed by kidney and fat, in which one-third to one-fourth of the hepatic PDI protein existed. The PDI protein band was also detected in heart and muscle. Fasting for 3 days decreased PDI protein levels in rat liver by 40%; control levels were recovered after 3 days of refeeding. The same change was observed in kidney. PDI activity, measured by the scrambled ribonuclease method, did not show the parallel alteration to PDI protein level in liver and kidney. Isomerase activity decreased to 50% of control values during fasting, but did not recover by refeeding. Thyroidal status did not affect either PDI protein level or isomerase activity. These findings show that fasting and refeeding affect PDI protein and enzyme activity, and that PDI protein level does not always reflect PDI activity.

Animals↗

In vitro assembly of the CENP-B/alpha-satellite DNA/core histone complex: CENP-B causes nucleosome positioning.

BACKGROUND: We have studied the nucleosome structure formed from alpha-satellite DNA bound with CENP-B and core histones, in order to develop a previous proposal that the CENP-B dimer may play a critical role in the assembly of higher order structures of the human centromere by juxtaposing CENP-B boxes in long alpha-satellite arrays. RESULTS: The dimeric structure of CENP-B was sufficiently stable to bundle together two 3.5 kbp DNA fragments when each DNA contained a CENP-B box. When the same length of DNA included two CENP-B boxes, the intra-molecular interaction with the CENP-B dimer predominated, resulting in the formation of loop structures. The in vitro assembly of CENP-B/alpha-satellite DNA/core histone complexes with the aid of nucleosome assembly protein-1 (NAP-1) permitted an investigation into the nucleosome arrangement in alpha-satellite DNA with CENP-B bound to CENP-B boxes. Footprint analyses with micrococcal nuclease (MNase) revealed that CENP-B causes nucleosome positioning between pairs of CENP-B boxes with unique hypersensitive sites created on both sides. CONCLUSION: We propose that CENP-B functions as a structural factor in the centromere region in order to establish a unique, centromere specific pattern of nucleosome positioning.

Autoantigens↗

Mouse skin reactions following fractionated irradiation with carbon ions.

PURPOSE: Skin reactions in the mouse leg following various daily doses given with 290 MeV/u carbon ions were investigated. MATERIALS AND METHODS: Seven different LET (linear energy transfer) values ranging from 14 to 100keV/microm were selected. The fractionation schedules were 1-, 2-, 4- and 8-daily fractions. The isoeffect doses to produce moist desquamation on the dose-response curves were calculated with 95% confidence limits. RESULTS: The isoeffect doses for carbon ions of 14 and 20 keV/microm increased with an increase in the number of fractions up to 4 fractions, but became constant when the number of fractions further increased to 8 fractions. This leveling off in isoeffect dose was more prominent for 40 keV/microm. Recovered dose per fraction was largest for 2 fractions of the 14keV/microm carbon beam. The isoeffect doses for 50, 60, 80 and 100keV/microm consistently increased with an increase in the number of fractions and did not show saturation up to 8 fractions. RBE (relative biological effectiveness) increased linearly with LET for all fractionation schedules. CONCLUSIONS: These results suggest that daily fractionation with carbon ions could spare radiation damage in patients, and that changes the fractionation schedule affect clinical outcome.

Animals↗

Secondary structures of synthetic peptides corresponding to the first membrane-contact portion of normal band 3 and its deletion mutant (Southeast Asian ovalocytosis).

The conformations of synthetic peptides corresponding to the first membrane-contact portion from Tyr390 to Lys430 of band 3 (band 3-1a) and the counterpart portion of South-East Asian ovalocytosis (SAO) band 3 (band 3-1b) in lipid bilayers were examined by means of circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy as well as a proteolytic digestion method. The CD and FTIR studies showed that band 3-1a and band 3-1b in a membrane lipid bilayer cannot assume an alpha-helix rich structure but instead assume a beta-structure rich conformation. The proteolytic digestion experiments demonstrated that the cleavage sites of Tyr392 and Phe423 were common to both the model and erythrocyte membranes. Taken together with our previous work, which indicated that the first membrane-contact portion was the portion embedded in the erythrocyte membrane without tight lipid-peptide interactions [Hamasaki et al. (1997) J. Biochem. 122, 577-585], we imply herein that the first membrane-contact portion of band 3 by itself can not assume the ordinary alpha-helix conformation in the membrane lipid bilayers. A proteinase-resistant portion, from Ser402 to Phe423, was observed when liposomes containing band 3-1a were digested with proteinase K, while no proteinase-resistant core portion was found in the case of band 3-1b (DeltaAla400-Ala408). This suggests the crucial role of the deleted portion, from Ala400 to Ala408, in the interaction of the first membrane-contact portion of band 3 with a membrane lipid bilayer.

Amino Acid Sequence↗

Functional and physical interaction between Rad24 and Rfc5 in the yeast checkpoint pathways.

The RFC5 gene encodes a small subunit of replication factor C (RFC) complex in Saccharomyces cerevisiae and has been shown to be required for the checkpoints which respond to replication block and DNA damage. Here we describe the isolation of RAD24, known to play a role in the DNA damage checkpoint, as a dosage-dependent suppressor of rfc5-1. RAD24 overexpression suppresses the sensitivity of rfc5-1 cells to DNA-damaging agents and the defect in DNA damage-induced Rad53 phosphorylation. Rad24, like Rfc5, is required for the regulation of Rad53 phosphorylation in response to DNA damage. The Rad24 protein, which is structurally related to the RFC subunits, interacts physically with RFC subunits Rfc2 and Rfc5 and cosediments with Rfc5. Although the rad24Delta mutation alone does not cause a defect in the replication block checkpoint, it does enhance the defect in rfc5-1 mutants. Furthermore, overexpression of RAD24 suppresses the rfc5-1 defect in the replication block checkpoint. Taken together, our results demonstrate a physical and functional interaction between Rad24 and Rfc5 in the checkpoint pathways.

Cell Cycle Proteins↗

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure.

To simulate the immediate hemodynamic effect of negative intrathoracic pressure during obstructive apneas in congestive heart failure (CHF), without inducing confounding factors such as hypoxia and arousals from sleep, eight awake patients performed, at random, 15-s Mueller maneuvers (MM) at target intrathoracic pressures of -20 (MM -20) and -40 cmH2O (MM -40), confirmed by esophageal pressure, and 15-s breath holds, as apneic time controls. Compared with quiet breathing, at baseline, before these interventions, the immediate effects [first 5 cardiac cycles (SD), P values refer to MM -40 compared with breath holds] of apnea, MM -20, and MM -40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 +/- 1. 9, 7.2 +/- 3.5, and 11.3 +/- 6.8 mmHg (P < 0.01); for systolic blood pressure (SBP), 2.9 +/- 2.6, -5.5 +/- 3.4, and -12.1 +/- 6.8 mmHg (P < 0.01); and for stroke volume (SV) index, 0.4 +/- 2.8, -4.1 +/- 2.8, and -6.9 +/- 2.3 ml/m2 (P < 0.001), respectively. Corresponding values over the last five cardiac cycles were for LVPtm 6.4 +/- 4.4, 5.4 +/- 6.6, and -4.5 +/- 9.1 mmHg (P < 0.01); for SBP 6.9 +/- 4.2, -8.2 +/- 7.7, and -24.2 +/- 6.9 mmHg (P < 0.01); and for SV index -0. 4 +/- 2.1, -5.2 +/- 2.8, and -9.2 +/- 4.8 ml/m2 (P < 0.001), respectively. Thus, in CHF patients, the initial hemodynamic response to the generation of negative intrathoracic pressure includes an immediate increase in LV afterload and an abrupt fall in SV. The magnitude of response is proportional to the intensity of the MM stimulus. By the end of a 15-s MM -40, LVPtm falls below baseline values, yet SV and SBP do not recover. Thus, when -40 cmH2O intrathoracic pressure is sustained, additional mechanisms, such as a drop in LV preload due to ventricular interaction, are engaged, further reducing SV. The net effect of MM -40 was a 33% reduction in SV index (from 27 to 18 ml/min2), and a 21% reduction in SBP (from 121 to 96 mmHg). Obstructive apneas can have adverse effects on systemic and, possibly, coronary perfusion in CHF through dynamic mechanisms that are both stimulus and time dependent.

Adult↗

Inferior vena caval thrombosis after traumatic liver injury.

We report here the case of a 35-year-old man who presented with inferior vena cava thrombosis (IVCT) after blunt hepatic trauma. The IVCT was incidentally detected by computed tomography (CT) 35 days after deep parenchymal suturing and suture approximation for liver lacerations. The patient denied any symptoms of thrombophlebitis. However, he had presented with significantly elevated values of FDP-D-dimer and a modest increase in plasminogen concentration, which indicated that he had been in a hypercoagulable and hypofibrinolytic state after the operation. He had not undergone any prophylactic anticoagulant therapy because of his concomitant subarachnoid hemorrhage and huge hepatic hematoma. The patient was treated with an emercy thrombectomy. Posttraumatic IVCT is extremely rare phenomenon. We should consider IVCT in patients with a severe hepatic injury, particularly if their coagulation system change into hypercoagulable and hypofibrinolytic state. Additionally, this case made us reflect on the treatment of traumatic liver injury.

Adult↗

Neural and hypotensive effects of angiotensin II receptor blockade.

Angiotensin II participates in the neural regulation of the heart and circulation at both central and peripheral sites. To explore the role of endogenous angiotensin II in blood pressure regulation, we conducted a randomized double-blind crossover trial in nine young healthy men (aged 33+/-3 [mean+/-SE] years) studied in the absence of salt restriction, comparing the effect of 1 week treatment with the angiotensin II receptor antagonist losartan (100 mg daily) against placebo with respect to the following variables, recorded during supine rest: intra-arterial blood pressure (BP), heart rate (HR), forearm vascular resistance and norepinephrine appearance rate, total body norepinephrine spillover, variability of BP and HR (spectral analysis), and baroreflex sensitivity for HR (gain of the transfer function from systolic BP to HR). Blood pressure was 119+/-7/66+/-4 mm Hg (systolic BP/diastolic BP) after 1 week of placebo and 112+/-6/61+/-3 mm Hg after 1 week of losartan (P<.05). Forearm vascular resistance tended to fall, from 42.3+/-6.9 U on placebo to 32.8+/-5.0 U with losartan treatment (P=.07). Losartan had no effect on HR (60+/-3 on placebo versus 59+/-2 beats per minute with losartan), total body norepinephrine spillover (3.0+/-0.8 versus 3.3+/-1.2 nmol/min), forearm norepinephrine appearance rate (3.8+/-1.1 versus 5.3+/-1.1 pmol/100 mL forearm tissue per minute), power in the high- or low-frequency components of the HR variability and BP variability spectra or on baroreflex sensitivity for HR. Endogenous angiotensin II contributes to the maintenance of supine BP in normal subjects, studied in the absence of sodium restriction. The fall in BP caused by losartan is accompanied by a resetting of the baroreflex regulation of HR and sympathetic outflow, but baroreflex sensitivity for heart rate is not altered. Therefore, the reduction in BP observed after short-term angiotensin type 1 receptor antagonism may be achieved through a direct effect on vascular tone rather than through a primary reduction in sympathetic outflow.

Adult↗

Synthesis and evaluation of water-soluble non-prodrug analogs of docetaxel bearing sec-aminoethyl group at the C-10 position.

To develop non-prodrugs of taxoids with satisfactory stability in vivo, high water-solubility, and potent antitumor activity, we prepared several 10-O-sec-aminoethyl docetaxel analogs (3) and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines, microtubule disassembly-inhibitory activity, and water-solubility. These analogs were synthesized from the 10-O-allyl baccatin derivatives (5a-c) using the beta-lactam synthon method. Among these analogs, the 10-O-(2-morpholinoethyl) (18, 21) and 10-O-(2-thiomorpholinoethyl) (19, 24) analogs exhibited cytotoxicity comparable or superior to that of docetaxel (2). In addition, the methanesulfonic acid salt (18a) had a high water-solubility.

Animals↗

A very-high-density lipoprotein with clotting ability from hemolymph of sand crayfish, Ibacus ciliatus.

A very-high-density lipoprotein (VHDL) with a density of 1.27-1.29 g/ml was the most abundant lipoprotein in the hemolymph of the sand crayfish Ibacus ciliatus. The VHDL isolated by a density gradient ultracentrifugation consisted of 94% protein and 6% lipid reflecting its high density, and phospholipid was a predominant lipid component. The VHDL had an apolipoprotein of molecular mass 195 kDa and its N-terminal amino acid sequence was identified as follows: LQPGLEYQYRYNGRVAA. This sequence was similar to those of clotting proteins from the spiny lobster Panulirus interruptus and the freshwater crayfish Pacifastacus leniusculus. Transglutaminase and Ca2+ also induced the VHDL to clot. Considering large amounts of VHDL in the hemolymph of sand crayfish, the VHDL not only functions as lipid carrier but plays an important role in the defense process of crustacea.

Amino Acid Sequence↗

Expression of costimulatory molecule CD80 on peripheral blood T cells in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the expression of costimulatory molecule CD80 on T cells of peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). METHODS: Monoclonal antibodies against CD80 were used for flow cytometry and expression of CD80 on PBMC was studied in 26 patients with SLE, 18 patients with rheumatoid arthritis (RA), 8 patients with mixed connective tissue disease (MCTD), and 22 healthy controls. RESULTS: CD80 was detected on CD3+ and CD19+ cells in patients with SLE and it was significantly higher than that of controls. In patients with SLE CD80 was expressed on CD4+ T cells (8.05+/-5.45%), significantly higher than in RA and controls, but was not highly expressed on CD8+ T cells (1.67+/-2.87%). CD80+CD4+ T cell phenotype analysis revealed CD45RA-, CD45RO+, and CD25+, or HLA-DR+ activated T cells. The percentage of CD80+ cells in CD4+ cells increased in the active stage of SLE, and was significantly correlated with the SLE disease activity index. CONCLUSION: CD80 can be expressed on activated CD4+ T cells in PBMC of patients with SLE in vivo and the appearance of these cells is associated with the disease activity in SLE.

Antibodies, Monoclonal↗

[Partial median sternotomy for pediatric cardiac surgery].

In order to minimize scar appearance and thereby improve postoperative cosmetic appearance for pediatric cardiac surgery patients, we performed partial median sternotomy incisions. A short midline incision, from 1 to 2 cm below the articular notch of the 2nd rib to the xiphoid process, was made. The sternum was divided from the xiphoid process to the articular notch of the 2nd rib. The thymus was mobilized and the pericardium incised longitudinally. The aorta and superior and inferior vena cava were mobilized to facilitate direct cannulations. Cardiopulmonary bypass was instituted in the usual fashion. From June to December 1997, 14 patients between the ages of 4 days and 12 years have undergone cardiac repair using this technique. Cases included 7 VSD (including 4 pulmonary hypertension and 1 DCRV), 5 ASD, 1 ECD and and 1 DORV with mitral atresia. All patients were extubated within 3 hours after surgery, and there were no wound infections or hospital mortalities (except one 4 day old baby who died by LOS on the 16th postoperative day). In our experience, this approach is safe and provides good exposure with excellent cosmetic results.

Cardiac Surgical Procedures↗

Mineral concentrations in the blood of male smokers and non-smoking males and females measured with fluoro-X-ray analyzer.

For clarification of the effects of smoking on mineral absorption in red blood cells (RBC) and serum, their concentrations at these sites were examined in ten male smokers and 12 male and 10 female non-smokers by fluoro-X-ray analysis. K in serum was high, and P, Ca and Fe low, compared to RBC. Mg and S in serum and RBC were essentially the same. S, Mg, P and K in RBC of smokers were higher than in male non-smokers, and Ca was lower. S and Ca in serum of smokers were significantly lower than in male non-smokers. P in smokers was higher than in non-smokers. P in RBC may possibly activate the reflux of Mg into RBC and may suppress that of Ca. In smokers, the correlation coefficient (gamma) between Fe and Ca was r = -0.68 in RBC, and r = 0.76 in serum. Also gamma between P and Mg was r = 0.4 in RBC and r = -0.48 in serum. Thus Fe in RBC may suppress the reflux of Ca. Mg and Ca in serum of females were significantly higher than in male non-smokers. Ca in RBC of females was significantly higher than in male non-smokers, and P, K and Fe were significantly lower. The product of Ca and P in RBC of females was lower than in male non-smokers, while in serum it was higher. gamma between P and Ca, and between Fe and Ca in RBC of females were negative, while they were positive in male non-smokers. The correlations in female RBC had the same pattern as in male smokers.

Adult↗

Spatial patterns of Ca2+ signals define intracellular distribution of a signaling by Ca2+/Calmodulin-dependent protein kinase II.

Ca2+ plays a central role in cell signaling, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of Ca2+ actions. The spatial distribution of intracellular Ca2+ signaling is not homogenous, rather it is dynamically organized, and it has been speculated that spatial patterns of Ca2+ signals may function as a form of cellular information transmitted to downstream molecules. To address this issue, we studied the intracellular distributions of the signalings by CaMKII and Ca2+ in the same astrocytes. The former was visualized by monitoring site-specific phosphorylation of a cytoskeletal protein vimentin, using site- and phosphorylation-specific antibodies, while the latter was examined by fura-2-based Ca2+ microscopy. Local Ca2+ signals induced vimentin phosphorylation by CaMKII localized in the same area. On the other hand, Ca2+ waves in astrocytes induced global phosphorylation of vimentin by CaMKII. A small population of vimentin filaments highly phosphorylated by CaMKII underwent structural alteration into short filaments at electron microscopic level. These results indicate that CaMKII transmits spatial patterns of Ca2+ signals to vimentin as cellular information. The possibility is discussed that spatial patterns of vimentin phosphorylation may be important for intracellular organization of vimentin filament networks.

Actin Cytoskeleton↗

A biotinylated perfringolysin O derivative: a new probe for detection of cell surface cholesterol.

theta-Toxin is a cholesterol-binding, pore-forming cytolysin of Clostridium perfringens. To detect cell surface cholesterol, we prepared a theta-toxin derivative, BC theta by biotinylation of a protease-nicked theta-toxin, which has the same binding affinity for cholesterol as theta-toxin without cytolytic activity. Human erythrocytes, V79 cells and human umbilical vein endothelial cells (HUVEC), were stained with BC theta coupled with FITC-avidin, and then the cells were analyzed by either flow cytometry or laser confocal microscopy. The fluorescence intensity increased in both intact and briefly fixed cells when treated with BC theta. BC theta-treated V79 cells were stained by neither trypan blue nor propidium iodide, indicating that BC stained just the outer surface of the plasma membrane of vital cells. Treatment of the cells with digitonin, a cholesterol-sequestering reagent, decreased the fluorescence intensity to the background level, indicating that BC theta staining is specific for cholesterol. The fluorescence intensity of erythrocytes pre-permeabilized with a small amount of theta-toxin increased more than ten-fold, suggesting higher cholesterol contents in the inner layer of the plasma membrane. When cells were cultured with cholesterol-depleted medium, the fluorescence intensity stained by BC theta decreased remarkably in V79 cells, but did not change in HUVEC. This indicates that cell surface cholesterol may be provided in different ways with these two cell lines. These results suggest that BC theta can be a useful probe for visualizing cell surface cholesterol and for evaluating the effects of cellular events on the topology and distribution of cholesterol.

Animals↗

Gangliosides enhance KCl-induced Ca2+ influx and acetylcholine release in brain synaptosomes.

Effects of gangliosides GM1 and GQ1b on cholinergic synaptic functions were investigated using synaptosomes prepared from mouse brain cortices. Treatment of synaptosomes with GM1 and GQ1b increased high K(+)-evoked acetylcholine (ACh) release in a bell-shaped dose-dependent manner. The peaks of the effects were found to be at 1-5 microM for GM1 and 5-10 microM for GQ1b. ACh synthesis and the levels of ACh in synaptosomes were not affected by the ganglioside treatment. Both gangliosides enhanced depolarization-induced influx of calcium ions into synaptosomes. These results indicate that GM1 and GQ1b gangliosides increase evoked ACh release by modulating voltage-dependent calcium channels in the synaptic plasma membranes. The effect of GM1 on calcium ion influx remained after repetitive washings, but was almost completely abolished when the bound GM1 was removed by trypsin. This indicates that the fraction of GM1 which was tightly bound to, but not incorporated in synaptic plasma membranes, is responsible for activating the calcium channels.

Acetylcholine↗