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Biomedical subjects

Y Takei

Publications and source records attributed to Y Takei.

At least 163 records · Page 9Linked to original sources
PubMed1996

B-type natriuretic peptide isolated from frog cardiac ventricles.

A new natriuretic peptide with 27 amino acid residues has been isolated from cardiac ventricles of the bullfrog, Rana catesbeiana. Since this ventricular peptide had high sequence identity to B-type (brain) natriuretic peptide (BNP), especially to chicken BNP (74%), we named it bullfrog BNP. Thus, semi-aquatic amphibians have tetrapod-type BNP, but do not seem to have fish-type ventricular natriuretic peptide (VNP) in their ventricles. Compared with other known BNPs, the C-terminus of bullfrog BNP was elongated by two amino acid residues and was not amidated. Bullfrog BNP dose-dependently decreased arterial blood pressure in the bullfrog with a potency twofold greater than that of human ANP. Bullfrog BNP also exhibited vasodepressor, natriuretic and diuretic activities in the rat, but it was 1/3, 1/7, and 1/17 as potent as human ANP in this mammalian species.

Amino Acid Sequence↗
PubMed1996

The predictive brain: anticipatory control of head direction for the steering of locomotion.

The control of head direction in humans walking along planned circular trajectories was investigated in this study. Five healthy volunteers were asked to walk at a constant speed along circular trajectories in the light and while blindfolded. Head and walking directions were analysed on a real-time basis. Head direction systematically anticipated changes in the direction of locomotion (by about 200 ms). The anticipation interval depended on the curvature of the circle. In the light, head orientation was deviated with respect to the walking direction, toward the inner concavity of the performed trajectory. The results suggest that head direction is controlled on a step-by-step basis in a predictive fashion. A 'go where you look' strategy seems to underlie steering along circular trajectories.

Adult↗
PubMed1996

The F(ab')2 fragment of an anti-ICAM-1 monoclonal antibody attenuates liver injury after orthotopic liver transplantation.

Long-term storage of liver grafts results in increased adhesion of leukocytes onto the sinusoidal walls. This eventually leads to posttransplant graft damage through disturbances of hepatic microcirculation. Intracellular adhesion molecule-1 (ICAM-1) is known to be involved in attachment of leukocytes. This study was designed to examine whether ICAM-1 participated in the pathogenesis of posttransplant liver injury. Inbred Lewis rats were used as both donors and recipients to avoid immunoreactivity. Donor livers were stored for either 1 or 6 hr in ice-cold Euro-Collins solution and subsequently implanted. Expression of ICAM-1 was examined immunohistochemically. In some rats that received livers stored for 6 hr, the intact IgG (1.0 mg/kg) or the F(ab')2 fragment (0.5 mg/kg) of an anti-ICAM-1 mAb (1A29) was administered via the tail vein immediately after reperfusion of portal blood. In the group receiving livers stored for 6 hr, ICAM-1 began to be expressed on the sinusoidal endothelial cells as early as 15 min after reperfusion of the portal blood. Strong ICAM-1 expression was observed from 2 hr up to 24 hr after reperfusion. In contrast, expression of ICAM-1 was not evident at any time point after surgery in the 1-hr storage group as well as in untransplanted, normal livers. Serum alanine aminotransferase (ALT) levels were significantly higher in the 6-hr storage group compared with those of the 1-hr storage group (1-hr: 171 +/- 9 IU/L; 6-hr: 825 +/- 109 IU/L, P < 0.05; mean +/- SEM) 24 hr after transplantation. Serum ALT levels were markedly reduced by treatment with the F(ab')2 fragment of 1A29 (247 +/- 34 IU/L, P < 0.05 vs. 6-hr storage group). This was associated with reduced accumulation of leukocytes in the liver. In marked contrast, treatment with the intact IgG of 1A29 increased serum ALT levels dramatically (5297 +/- 634 IU/L, P < 0.05 vs. 6-hr storage group) and reduced serum complement. Histological examination revealed focal hepatocellular necrosis 24 hr after surgery in the 6-hr storage group. Treatment with the F(ab')2 fragment decreased the liver damage; in marked contrast, treatment with the intact IgG strikingly aggravated the injury, as characterized by massive necrosis throughout the liver. Liver damage caused by the intact IgG might be related to activation of the complement system by the Fc portion of the antibody. Taken together, these results indicate that ICAM-1 is involved in the mechanism of postoperative liver injury following liver transplantation.

Animals↗
PubMed1996

Liposome-encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro.

Dichloromethylene diphosphonate (MDPCl2) encapsulated in multilamellar liposomes was selectively incorporated by macrophages, immediately transferred to lysosomes, then released from liposomes into lysosomes by enzymatic digestion of the liposomal lipid layers. From 4 h after ingesting liposome-encapsulated MDPCL2 murine macrophages in vivo and in vitro acquired the ultrastructural features of apoptosis, such as condensed nuclear chromatic, nuclear fragmentation, cell shrinkage, and blebbing of the plasma membrane. Murine peritoneal macrophages and isolated rat Kupffer cells incubated in the medium containing liposome-encapsulated MDPCl2 increased DNA fragmentation in a dose-dependent manner. Electrophoretic analysis of extracted DNA from the isolated Kupffer cells showed DNA fragmentation. Another diphosphonate, Alendronate (4-amino-1-hydroxy-butylidene-1,1-diphosphonate) had less potent macrophage cytotoxicity. However, MDPCl2, Alendronate, and gadolinium chloride in solution were not cytotoxic to macrophages. These results implied that the intralysosomal accumulation of MDPCl2 generates signals to induce macrophage apoptosis.

Alendronate↗
PubMed1996

Atrial and ventricular natriuretic peptide concentrations in plasma of freshwater- and seawater-adapted eels.

Plasma levels of atrial and ventricular natriuretic peptide (ANP and VNP) were measured in freshwater (FW)- and seawater (SW)-adapted eels using homologous radioimmunoassays. Anesthesia with tricaine (MS222) and exposure of the pericardium for blood sampling from the ventral aorta affected plasma ANP and VNP levels. ANP and VNP levels in the ventral aorta were higher than those in the dorsal aorta when blood was collected simultaneously from both aortae of cannulated conscious FW eels, perhaps reflecting branchial extraction of the peptides. This phenomenon was not observed in SW eels. Based on these results, blood was sampled from conscious eels through a catheter implanted in the ventral aorta because it appears to reflect most accurately ANP secretion. Plasma ANP and VNP levels measured in more than 100 conscious FW and SW eels displayed large variations at each month despite acclimation to laboratory conditions at 180 for more than 1 week in FW eels or for more than 2 weeks in SW eels. However, concentrations of ANP and VNP averaged from all data were not different between FW and SW eels: 68.1 +/- 2.9 (FW: n = 155) vs 60.7 +/- 3.6 (SW: n = 104) for ANP, 51.6 +/- 3.0 (FW: n = 69) vs 55.0 +/- 3.7 (SW: n = 54) for VNP (fmol/ml in each case). Plasma Na concentration and osmolality were significantly higher in SW eels than in FW eels. Plasma ANP and VNP levels thus do not seem to be affected by chronic changes in plasma Na concentration and osmolality.

Adaptation, Physiological↗
PubMed1996

Changes in plasma atrial and ventricular natriuretic peptide concentrations after transfer of eels from freshwater to seawater or vice versa.

Changes in plasma atrial and ventricular natriuretic peptide (ANP and VNP) concentrations were examined in conscious eels, Anguilla japonica, after transfer from freshwater (FW) to seawater (SW) or vice versa. These changes were compared in ventral and dorsal aortic blood since clearance receptors are present in the gills. Plasma Na concentration and osmolality in the ventral aortic blood rose linearly after transfer of FW eels to SW. Six hours after transfer, plasma ANP levels increased from 28.1 +/- 2.9 to 44.8 +/- 5.4 fmol/ml (n = 6) (P < 0.05) and plasma VNP levels also increased from 63.6 +/- 3.8 to 91.2 +/- 6.2 fmol/ml (n = 6) (P < 0.05). However, the levels gradually returned to the FW levels despite plasma Na concentration and osmolality remaining elevated. Dorsal aotic plasma ANP and VNP levels were unchanged after transfer of FW eels to SW, possibly due to extraction of secreted peptides by the branchial clearance receptors. After transfer of SW-adapted eels to FW, plasma ANP and VNP levels were unchanged, while both plasma Na concentration and osmolality decreased. These results indicate that plasma ANP and VNP levels are increased by an increase in plasma Na concentration or osmolality after transfer of FW eels to SW. However, the sustained increase in plasma Na concentration or osmolality no longer stimulated ANP and VNP secretion, and plasma ANP and VNP levels gradually returned to the FW levels gradually on adaptation to SW.

Adaptation, Physiological↗
PubMed1996

Multiple osteocartilaginous exostosis. A follow-up study.

Deformity of the lower extremities in 26 patients with multiple cartilaginous exostosis was examined radiologically. Follow-up periods ranged between 3 and 33 years (mean 10.3 years). Twenty-four patients had deformity of the joints. A femoral neck-shaft angle (FNA) of more than 150 degrees was noted in 14 patients (26 of 51 hip joints) at diagnosis. After approximately 10 years of age, the FNA tended to decrease. Eleven patients (22 of 52 knee joints) had genu valgum (the femorotibial angle < mean -2 SD of normal control) which was caused by valgus deformity of the distal femur in one-third of the patients and that of the proximal tibia in two-thirds. Fifteen of 21 patients (29 of 42 joints) had valgus deformity of the ankle (antero-posterior mortise angle of the ankle > 94 degrees), and in half of them, the valgus deformity progressed with growth. Two patients (aged 10 and 11 years) underwent varus osteotomy of the tibia with partial excision of the fibula. However, their deformity relapsed. Surgical treatment for hip deformity is unnecessary during the growth stage. Progressive deformity of the knee and ankle should be detected in an early stage, and the surgical indication has to be examined.

Adolescent↗
PubMed1996

Determination of bradykinin-(1-5) in inflammatory exudate by a new ELISA as a reliable indicator of bradykinin generation.

We have developed an ELISA for BK-(1-5) (Arg1-Pro2-Pro3-Gly4-Phe5). In rat carrageenin-induced pleurisy, in which a plasma exudation peak was observed 5 h after carrageenin, BK levels in the exudates were negligible (< 60 pg/rat). BK-(1-7) (des-Phe8-Arg9-BK) was detectable (900-400 pg/rat) over the entire course of the inflammation. However, a larger amount of BK-(1-5) was detectable in association with the increase in plasma exudation, showing a peak (8800 +/- 1200 pg/rat) 3 h after carrageenin. Bromelain (10 mg/kg, i.v.) and soy bean trypsin inhibitor (0.3 mg/rat, intra-pleural) significantly reduced BK-(1-5) levels (by 60-93%, 3, 7 and 19 h after carrageenin) and plasma exudation rates (by 61-74%, 3 and 7 h after carrageenin). Dexamethasone (0.3 mg/kg, i.p.) reduced BK-(1-5) levels (by 78%) and decreased plasma exudation (by 70%) 3 h after carrageenin. In nasal allergy patients, antigen challenge of nasal mucosa elevated BK-(1-5) levels and active kallikrein levels in nasal washes. These results verify that BK-(1-5) determined by ELISA is a good indicator for release of kinins in vivo.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Lack of contribution of circulatory kinin elevated by captopril to induce hypotension in normotensive and hypertensive rats.

Captopril (10 mg/kg, i.p.) increased the arterial bradykinin (BK) level (Art-BK) of non-treated Sprague-Dawley rats (SD), determined by an ELISA, from 10.8 +/- 3.2 pg/ml to 32.9 +/- 5.4 pg/ml significantly (p < 0.05, n = 6). Intravenous infusion of BK (100-3000 ng/kg/min) dose-dependently increased heart rate (HR) and decreased mean blood pressure (MBP), the former at lower doses than the latter, and the hypotensive response became significant at 3000 ng/kg/min. Art-BK determined during infusion of the lowest dose of BK (100 ng/kg/min) was 12 times the endogenous Art-BK after captopril administration. In spontaneously hypertensive rats, Wistar Kyoto rats, and deoxycorticosterone acetate-salt treated hypertensive rats, Art-BK (450-1280 pg/ml) determined during intravenous BK-infusion (1000-3000 ng/kg/min), which induced significant hypotension, was 20 to 100 times the endogenous Art-BK (4.5-64 pg/ml) with captopril treatment. These results suggest that the increased Art-BK due to inhibition of kinin degradation by captopril could not account for the hypotension due to this angiotensin converting enzyme inhibitor in normotensive and hypertensive rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Quantitative analysis of human walking trajectory on a circular path in darkness.

Thirteen normal (eight young and five older) subjects and a patient who was removed left sided acoustic neurinoma were tested to walk blindfolded along circular paths. They were asked to walk completing two revolutions and to stop when they judged they had returned to the initial position with their head faced to the initial directions. Movements of two markers on the subjects head were recorded by three dimensional motion analyzing system (ELITE system) at 50 Hz which allowed us to measure (a) total walked distance, (b) average radius of the trajectory, and (c) cumulative angle of rotation. Eight young subjects were tested on three circles with radii 0.5, 0.9, and 1.15 m, in two conditions (control, and with mental arythmetic), only to clockwise direction. Five older subjects and a patient were tested on a circle of 0.9 m radius in two conditions, but to both directions, counterclockwise and clockwise. Walked trajectories of young subjects were smooth, whereas those of older subjects tended to be polygonal. Young subjects overshot the ideal distance (6.6%) and ideal radius (9.5%), whereas they undershot the ideal angle (5.1%). There was no effect of circle size or condition on these variables. On the other hand, there was a significant effect of condition on average radius in the older group. The performance of older subjects seemed to be affected by the concurrent mental task. Comparing the counterclockwise walk, the older subjects undershot the turning angle much more than the young subjects which suggest deficits in the vestibular function with aging. The patient showed larger radius and smaller angle while she turned to the healthy side (clockwise) than to the affected side (counterclockwise). Lack of unilateral vestibular information seemed to have affected the circular walking trajectory.

Adult↗
PubMed1996

Evidences for involvement of cyclooxygenase-2 in proliferation of two gastrointestinal cancer cell lines.

Cyclooxygenase (COX) consists of two isozymes, COX-1 and COX-2. The roles of these isozymes in the gastrointestinal tract are unknown. We investigated messenger RNA expression of the COX-1 and COX-2 genes in the gastrointestinal cancer cell lines MKN28, MKN45, KATO III CACO-2, DLD-1 and LoVo. These cell lines expressed comparable levels of COX-1 mRNA, although their expression of COX-2 varied. Therefore, we studied the effects of NS-398 and indomethacin, specific and non-specific inhibitors for COX-2, on proliferation of the cell lines. Both of the inhibitors suppressed proliferation of the two cell lines that highly expressed COX-2 (MKN45 and CACO-2). However, these inhibitors exerted minimal effects on proliferation of the other cell lines, which expressed significantly lower levels of COX-2. Therefore, it was proposed that COX-2 participates in proliferation of cancer cells because of over expression of the COX-2 gene.

Cell Division↗
PubMed1996

Modification of beta 2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.

beta 2microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGEs). We demonstrated that AGE was localized to amyloid deposits in patients with DRA by immunohistochemistry using a monoclonal anti-AGE antibody. To clarify the mechanism of AGE modification of beta 2m-amyloid, we studied the effects of 3-deoxyglucosone (3-DG), a potent protein crosslinking the intermediate of the Maillard reaction, on the AGE modification of beta 2m, and quantified the serum levels of 3-DG in patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), and undialyzed patients. The serum levels of 3-DG were markedly increased in the dialyzed and undialyzed uremic patients. Although the serum level of 3-DG decreased after HD with a mean reduction rate of 67%, it was still significantly higher than in normal serum. Incubation of beta 2m with 3-DG at 37 degrees C emitted fluorescence characteristic for AGE, and caused AGE modification and dimer formation of beta 2m as demonstrated by Western blotting using the same monoclonal anti-AGE antibody used for immunohistochemical demonstration of AGE in DRA. The AGE-modified dimer of beta 2m could be extracted from the amyloid tissue of a patient with DRA. 3-DG showed more intense and faster reactivity with beta 2m to form AGE and dimer as compared with glucose, and aminoguanidine suppressed the AGE and dimer formation of beta 2m by 3-DG. In conclusion, 3-DG accumulating in uremic serum may be involved in the AGE modification of beta 2m-amyloid.

Amyloidosis↗
PubMed1996

Amyloid beta 2-microglobulin is modified with N epsilon-(carboxymethyl)lysine in dialysis-related amyloidosis.

Recent work from this laboratory revealed that advanced glycation end product was localized to amyloid deposits in patients with dialysis-related amyloidosis by immunohistochemistry using a monoclonal antibody to advanced glycation end product. To elucidate the epitope of the antibody, N alpha-p-tosyl-L-lysine-methyl ester was incubated with glucose in vitro, and then a compound reactive to the antibody was purified from the incubate by buthanol extraction, XAD-2 column chromatography, and high-performance liquid chromatography while the reactivity was examined by enzyme linked immunosorbent assay. The purified compound was identified as N epsilon-(carboxymethyl)-N alpha-p-tosyl-L-lysine-methyl ester by using secondary ion mass spectrometry, and 1H- and 13C-nuclear magnetic resonance spectroscopy. The epitope of the antibody was identified as -CH2-NH-CH2-COOH by enzyme-linked immunosorbent assay of compounds with structures similar to N epsilon-(carboxymethyl)lysine. Immunochemical study using the antibody demonstrated the presence of N epsilon-(carboxymethyl)lysine in the beta 2-microglobulin dimer (molecular weight 23929) isolated from the synovium amyloid of a hemodialysis patient with dialysis-related amyloidosis. In conclusion, amyloid beta 2-microglobulin is modified with N epsilon-(carboxymethyl)lysine in dialysis-related amyloidosis.

Amyloid↗
PubMed1996

A comparison of techniques used by elite gymnasts in performing the basket-to-handstand mount.

Twenty-six subjects were selected from 25 American and 28 Japanese gymnasts filmed during their respective 1990 national championships. The 13 highest (Group 1) and 13 lowest (Group 2) scored basket-to-handstand mounts on the parallel bars were compared. It was hypothesized that there would be significant differences between the kinematics demonstrated by the gymnasts from the two groups and that differences in the early preparatory phases would account for most of the differences in the resulting movements. The results revealed significant differences (P < 0.005) between the two groups, with Group 1 achieving greater vertical displacement of the centre of mass during the upward inverted swing and larger vertical velocity at bar release; greater backward horizontal motion of the centre of mass and forward body rotation in the flight phase; and a higher body centre of mass at bar regrasp with greater fluency of upward body motion into the handstand position. There were no significant differences between the two groups in the performance of the jump to end of backward swing and forward swing to maximum body pike that could be attributed to the differences in the last three phases. Based on the findings of this study, successful performance is likely when the arm pull is sustained with maximum effort until the body centre of mass and the trunk are well above the bars to enable the bar release with high body centre of mass, high body angle, large vertical velocity, backward horizontal velocity and forward angular momentum. This brings about (1) the desired direction of linear motion of centre of mass and (2) high body centre of mass and high body angle close to the handstand position at bar regrasp, which together ensure the fluency of upward body motion into the final position.

Biomechanical Phenomena↗
PubMed1996

D-mannose dimer introduced human recombinant interleukin- 1 alpha, NEO IL-1 alpha, exhibits altered tissue distribution in mice.

Previous studies have demonstrated that the carbohydrate-introduced recombinant human IL-l alpha exhibited impairment in both biologic activities in all the experiments in vitro and receptor binding capacity compared with intact IL-l alpha. However, the glycosylated IL-l alpha exhibited selective activities in vivo. In this study, we compared the tissue distribution of IL-l alpha and IL-l alpha coupled with D-Mana (l-6)Man [Man2 alpha) (l-6)IL-l alpha] in mice. Mice were injected by intravenous and intraperitoneal routes with 2.0 mu g radiolabeled IL-l alpha. At 1 and 2 h after IP injection, the level of Man2 alpha) (l-6)IL-l alpha decreased twofold compared with that of IL-l alpha in kidney. In contrast, at 1 hour after administration, Man2 alpha) (l-6)IL-l alpha exhibited higher levels than IL-l alpha in blood, heart, and liver. No significant difference was observed in brain at each time point. IV injection demonstrated that Man2 alpha)(l-6)IL-l alpha decreased to approximately one-half the level of rhIL-l alpha in kidney. In contrast, Man(2 alpha) (l-6)IL-l alpha increased twofold over that of IL-l alpha in liver at 1 h after dosing. These findings are consistent with the result of IP injection. There was no significant difference between IL-l alpha and glycosylated IL-l alpha at 4 h after IV administration. These differences in tissue distribution may contribute to the selective activities of glycosylated IL-l alpha in vivo. The results also suggest that by coupling with mannose dimer, it is possible to develop neocytokines prone to liver distribution.

Animals↗
PubMed1996

Phase I study of a carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

Cisplatin (CDDP)-containing chemotherapy has become the mainstay of clinical trials in unresectable non-small-cell lung cancer (NSCLC), but the role of chemotherapy in the routine management of NSCLC remains controversial. We conducted a phase I study with the combination carboplatin (CBDCA), CDDP, and etoposide (Etop) in unresectable NSCLC. CBDCA, at a starting dose of 80 mg/m2, on day 1, was combined with a fixed dose of CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3). Escalation was performed after four patients entered at each dose level. If no World Health Organization (WHO) grade 4 toxicity developed after the first cycle in more than half of the patients or WHO grade 3/4 toxicity in more than two thirds, the dose was escalated. The maximum tolerated dose was established at 300 mg/m2 for CBDCA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. No grade 3/4 nonhematologic toxicities were seen. The recommended dose of CBDCA to be combined with CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3) is 280 mg/m2. This trial suggests that our combination chemotherapy may be effective in patients with advanced NSCLC. A multicenter phase II study based on these findings is now under way.

Adult↗
PubMed1996

Gastric mucosal energy metabolism and intracellular mucin content changes in patients with liver cirrhosis.

Biopsy samples from patients with liver cirrhosis were investigated for changes in gastric mucosal energy metabolism and intracellular mucin content using high performance liquid chromatography and an image analysing system. The test group consisted of eight non-cirrhotic patients with endoscopically normal mucosa (controls) and eight cirrhotic patients with oesophageal varices. The amount of ATP, energy charge level and intracellular mucin content were all significantly decreased in cirrhotic patients when compared with those of the controls. The decrease in energy charge also correlated well with the decrease in intracellular mucin content in the gastric mucosa. The results indicate that gastric mucosal energy metabolism is impaired in cirrhotic patients concomitantly with a decrease in the intracellular mucin content in the gastric mucosa. These changes may weaken defensive mechanisms against acid and NSAID, resulting in gastric mucosal injury in cirrhotic patients.

Adenosine Diphosphate↗