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Biomedical subjects

Y Takei

Publications and source records attributed to Y Takei.

At least 145 records · Page 8Linked to original sources

Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis.

We have recently demonstrated by immunohistochemistry that amyloid beta 2-microglobulin (beta 2m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the beta 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.

Aged↗

A 'kickout' double salto backward tucked dismount from the horizontal bar performed by elite gymnasts.

The aim of this study was to identify the differences in the tucked and extended body positions, and in the spatiotemporal characteristics of the motion of the centre of mass, during the performance of kickout and non-kickout double salto backward tucked dismounts. A 16-mm camera, operating at 100 Hz, was used to record double salto backward tucked dismounts during the 1990 national championships in Japan and the USA. A high-scoring kickout group (n = 24) had a significantly (P < 0.005) higher body centre of mass at the tightest tuck position in the first salto, and shorter time to achieve maximum body extension during the second salto, than did a low-scoring non-kickout group (n = 24). Furthermore, the kickout group showed greater height of body centre of mass, larger normalized moment of inertia, and smaller body angle from the vertical at maximum body extension. Consequently, they had longer duration and larger distances of flight than the non-kickout group in which to display the maximum body extension before landing on the mat. It was concluded that the kickout double salto backward tucked dismount is indeed more effective than the non-kickout dismount because it involves (a) greater body extension in an inverted position before passing through the vertical and (b) greater heights of centre of mass at the peak of flight, at the tightest tuck and at maximum body extension. Furthermore, this dismount enhances the display of virtuosity for which bonus points are awarded. The results suggest that this kickout dismount may be helpful in developing the mechanical foundation necessary for learning more advanced dismounts, such as the triple salto backward tucked and double salto backward stretched, with increased effectiveness and safety.

Biomechanical Phenomena↗

A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.

Adult↗

Expression of the cyclooxygenase-2 gene in gastric epithelium.

This study examined the mRNA level of cyclooxygenase-2 (cox-2) in a rat gastric mucosal cell line after growth stimulation in vitro and in rat gastric mucosa before and after acid-induced injury in vivo. RGMI cells were stimulated with fetal calf serum in the in vitro study. Thereafter, the cox-2 mRNA level was examined by Northern analysis. Effects of NS-398, a specific inhibitor of cox-2, and indomethacin on prostaglandin production and cell proliferation were examined in RGM1 cells. In the in vivo study, rats were given 1 ml of 0.6 N hydrochloric acid into the stomach. The level of cox-2 mRNA was examined in rat gastric mucosa after acid administration. Cox-2 mRNA increased 20-60 min after growth stimulation in RGM1 cells. Both NS-398 and indomethacin suppressed prostaglandin production and cell proliferation after growth stimulation. Expression of cox-2 mRNA was observed 40 and 60 min after administration of 0.6 N HCl. Gastric lesions developed within 60 min after HCl administration and healed significantly within 48 h. The present study shows the expression of cox-2 in gastric epithelial cells in vitro and in gastric mucosa after injury in vivo. The results also suggest that cox-2 is involved in de novo synthesis of prostaglandins and cell proliferation in gastric epithelium.

Animals↗

Effects of natriuretic peptides and nitroprusside on venous function in trout.

Active venous regulation of cardiovascular function is well known in mammals but has not been demonstrated in fish. In the present studies, the natriuretic peptides (NP) rat atrial natriuretic peptide (ANP) and trout ventricular natriuretic peptide (VNP), clearance receptor inhibitor SC-46542, and sodium nitroprusside (SNP) were infused into unanesthetized trout fitted with pressure cannulas in the ventral aorta, dorsal aorta, and ductus Cuvier, and a ventral aorta (VA) flow probe was used to measure cardiac output (CO). In another group, in vivo vascular (venous) capacitance curves were obtained during ANP or SNP infusion. The in vitro effects of NP on vessels and the heart were also examined. ANP, VNP, and SC-46542 decreased central venous pressure (PVen), CO, stroke volume (SV), and gill resistance (RG), whereas systemic resistance (RS) and heart rate (HR) increased. Dorsal aortic pressure (PDA) transiently increased and then fell even though RS remained elevated. ANP decreased mean circulatory filling pressure (MCFP), increased vascular compliance at all blood volumes, and increased unstressed volume in hypovolemic fish. ANP had no direct effect on the heart. ANP responses in vivo were not altered in trout made hypotensive by prior treatment with the angiotensin-converting enzyme inhibitor lisinopril. SNP reduced ventral aortic pressure (PVA), PDA, and RS, increased CO and HR, but did not affect PVen, SV, or RG. SNP slightly decreased MCFP but did not affect compliance or unstressed volume. In vitro, large systemic arteries were more responsive than veins to NP, whereas SNP relaxed both. These results show that, in vivo, NP decrease venous compliance, thereby decreasing venous return, CO, and arterial pressure. Conversely, SNP hypotension is due to decreased RS. This is the first evidence for active regulation of venous capacitance in fish, which probably occurs in small veins or venules. The presence of venous baroreceptors is also suggested.

Animals↗

Isolation and mapping of a human zinc finger gene (ZNF188) homologous to ZNF187, a serum-response-element binding protein.

From a human pancreas cDNA library we isolated and characterized a novel zinc finger gene encoding a protein homologous to ZNF187, a serum response element-binding protein. The full-length cDNA contained an open reading frame of 1,686 nucleotides encoding a predicted 562-amino-acid peptide that included an ATP-GTP binding site and seven C2H2 zinc finger domains. The consensus sequence of the C2H2 domains (CX2CX3FX5LX2HX3H) is common in the SRE-binding region present in Drosophila Krüppel proteins. An alternatively spliced form of the transcript found in the cDNA library lacked both the ATP-GTP binding site and any C2H2 zinc finger domains. We localized this gene (ZNF188) to chromosome band 7q22.1-->q22.3 by fluorescence in situ hybridization.

Amino Acid Sequence↗

Molecular cloning of a novel gene similar to myeloid antigen CD33 and its specific expression in placenta.

We have isolated a novel gene that encodes a protein sharing significant similarity with myeloid antigen CD33. The complete cDNA contains an open reading frame of 1,326 nucleotides encoding 442 amino acids. The deduced amino acid sequence indicates that this molecule belongs to the immunoglobulin (Ig) superfamily and is likely to be a new member of the sialoadhesin sub-family. It is composed of three Ig-like domains; its high degree of similarity to CD33 (70% identity) in the first and second of these domains implies that the placenta-specific gene product is likely to be associated with cell-cell interaction. Northern-blot analysis revealed transcripts of four distinct sizes, 7.5 kb, 5.0 kb, 4.1 kb, and 2.0 kb, specifically in the placenta. Consequently, we termed this gene CD33L (CD33 antigen-like). An alternatively-spliced transcript encoding a 342-amino-acid peptide which lacked the transmembrane region and the cytoplasmic tail was also isolated. We mapped CD33L by fluorescence in situ hybridization (FISH) to human chromosome 19q13.3, where the CD33 gene is also located.

Alternative Splicing↗

Characterisation of natriuretic peptide receptors in eel gill.

A radioligand-binding assay was established for eel atrial natriuretic peptide (eANP), and ANP receptors were characterised in the eel gill. ANP binding to the gill membrane fraction was saturable with increasing ligand concentrations and was specific to ANP peptides, i.e. eANP, ventricular natriuretic peptide (VNP) and C-type natriuretic peptide (CNP). A Scatchard analysis revealed a single class of high-affinity receptors with a Kd of 59.2 pM and a Bmax of 67.9 fmol/mg protein. The Kd value is within the range of plasma ANP concentration of the eel. Kd and Bmax did not differ between freshwater (FW)- and seawater (SW)-adapted fish. The gill receptors exhibited similar affinity for eANP, eVNP and eCNP, and ANP binding was almost completely displaced by C-ANF, a specific ligand for guanylate cyclase-uncoupled receptors. The presence of this type of receptor (natriuretic peptide receptor (NPR)-C and NPR-D) was also indicated in eel gill by affinity labelling. cGMP production was stimulated by the addition of eCNP but not by eANP and eVNP, and this was observed only in FW eels. Thus, most ANP receptors in eel gill are NPR-C and NPR-D, but a small number of the NPR-B type are also present in FW eels. In addition to the gill, specific ANP receptors were detected in the red body of the swim bladder, the brain, digestive tracts, kidney, head kidney and urinary bladder, in most of which ANP action has been reported. The density of ANP receptors decreased in most tissues after adaptation to SW except the gill, brain, atrium and spleen.

Adaptation, Physiological↗

Effects of homologous atrial, brain, and C-type natriuretic peptides on isolated heart and blood vessels of bullfrog.

The cardiovascular effects of homologous natriuretic peptides (fNPs) were examined in the bullfrog, Rana catesbeiana. Synthetic bullfrog atrial natriuretic (fANP), brain natriuretic (fBNP) and C-type natriuretic peptides (fCNP I and fCNP II), were tested in vitro and compared under the same experimental conditions. All frog NPs produced a significant, and concentration-dependent, reduction in tension (relaxant effect) in the isolated dorsal aorta. Frog CNP II exhibited similar vasorelaxation profile as that of fANP, while fBNP and fCNP I had lower activity than fANP. Frog NPs inhibited norepinephrine induced contraction and fCNP II was most potent. In isolated preparations of atrium and ventricle, fCNP I and II produced a significant, and concentration-dependent, reduction in tension, but neither fANP nor fBNP produced any significant effects. Frog CNP II is most potent among fNPs in relation to reduce the cardiac output. Chronotropic responses of the heart to administrations of NPs were insignificant. The present results for the first time showed that fNPs play roles in the control of cardiovascular system, both blood vessels and heart, in the bullfrog.

Animals↗

Cloning, sequence analysis, tissue-specific expression, and prohormone isolation of Eel atrial natriuretic peptide.

A complementary DNA (cDNA) encoding eel atrial natriuretic peptide (ANP) precursor was specifically amplified from eel atrial mRNAs by rapid-amplification polymerase chain reaction. The sequence analysis of the cDNA using multiple clones revealed that the preproANP consists of 140 amino acid residues carrying a signal sequence at its N-terminus and a mature ANP at its C-terminus. An additional glycine residue was attached to the C-terminus of previously isolated eel ANP. The glycine residue may be used for amidation of the C-terminus or removed after processing. The cleavage site of a signal peptide with 22 amino acid residues was confirmed by isolation of proANP protein from eel atria. The proANP sequence deduced from the cDNA was also confirmed for 71% of the isolated protein. Sequence comparison with other natriuretic peptides revealed that eel ANP is more similar to mammalian ANP than to B-type natriuretic peptide (BNP) at both amino acid and nucleotide sequence levels. The eel ANP gene was a single copy gene as shown by Southern blot analysis. Northern blot analysis showed that eel ANP mRNA is approximately 0.8 kb in size and exclusively detected in the atrium. Thus, eel ANP is a true atrial hormone judging from both the sequence and the site of production. However, reverse transcription-polymerase chain reaction detected ANP message in the brain, gill, cardiac ventricle, red body of swim bladder (rete mirabilis), intestine, head kidney (including interrenal and chromaffin tissues) and kidney. Most of these tissues are involved in ion and/or gas exchange in fishes.

Amino Acid Sequence↗

Endothelin-1 in the gastric mucosa in stress ulcers of critically ill patients.

OBJECTIVE: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators causing this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1), a potent vasoconstrictive peptide, in stress ulcers in critically ill patients. METHODS: Using sandwich enzyme immunoassay, we measured ET-1 content in plasma and the gastric mucosa of 16 critically ill patients with traumatic head injury on admission and of 11 healthy subjects. Gastric mucosal samples were obtained endoscopically. When gastric drainage contained occult blood, endoscopic examination was performed again, and ET-1 concentrations in injured and adjacent normal mucosa were compared. RESULTS: Plasma and mucosal ET-1 concentrations were significantly higher in critically ill patients on admission (6.1 +/- 0.6 pg/ml and 13.8 +/- 1.6 ng/g, respectively) compared with values in control subjects (2.7 +/- 0.4 pg/ml and 8.2 +/- 0.5 ng/g, respectively) (p < 0.01). The mucosal ET-1 concentration tended to be elevated in patients who had experienced hypoxia compared with those who had not (p = 0.07). In five patients who were again examined endoscopically, the ET-1 concentration in the injured mucosa was significantly higher than that in adjacent mucosa (19.2 +/- 3.2 and 10.1 +/- 1.6 ng/g, respectively; p < 0.05). CONCLUSIONS: These results suggest that endogenous ET-1 plays an important role in the local pathogenesis of stress ulcers, especially those caused by hypoxia.

Adult↗

Influence of blood substrate levels on myocardial kinetics of iodine-123-BMIPP.

UNLABELLED: To evaluate the influence of blood substrate levels on myocardial uptake of 123I-labeled beta-methyl-iodophenyl-pentadecanoic acid (BMIPP), we examined the correlation between myocardial BMIPP uptake and blood levels of free fatty acid (FFA), glucose, insulin, triglyceride and total cholesterol. METHODS: In 180 patients, venous blood samples were obtained, and the early and late myocardial uptakes (MU15 and MU150) were determined on planar images at 15 and 150 min after injection at rest, respectively, and the clearance rate of BMIPP from the myocardium was calculated. Dynamic SPECT with BMIPP, PET with [18F]fluoro-deoxyglucose and determination of myocardial carnitine contents were performed in 15, 1 and 3 patients, respectively. RESULTS: In the 180 patients, MU15 correlated with blood insulin (r = 0.22, p = 0.005) and FFA (r = -0.19, p = 0.02) levels, whereas MU150 did not correlate with blood levels of any variables that were measured (p > 0.05). The clearance rate correlated with blood insulin (r = 0.28, p < 0.001), glucose (r = 0.17, p = 0.03) and FFA (r = -0.40; p < 0.001) levels. The correlations were, however, weak, and five patients (2.8%) with no myocardial BMIPP uptake, all of whom had anterior myocardial infaction, had no characteristics regarding the blood substrate levels. Although dynamic SPECT demonstrated rapid myocardial extraction of BMIPP in 13 patients with myocardial BMIPP uptake, it demonstrated no myocardial BMIPP extraction in two patients with no myocardial BMIPP uptake. One of the five patients with no myocardial BMIPP uptake showed increased myocardial [18F]fluorodeoxyglucose uptake and decreased myocardial carnitine content. CONCLUSION: The influence of blood substrate levels on myocardial BMIPP uptake is not very significant, although high serum FFA levels may be associated with slow clearance of BMIPP from the myocardium. The complete absence of myocardial BMIPP uptake is not rare and may not be associated with changes in blood substrate levels or early back diffusion of BMIPP.

Adolescent↗

Protection by Carolina rinse solution, acidotic pH, and glycine against lethal reperfusion injury to sinusoidal endothelial cells of rat livers stored for transplantation.

The critical injury causing graft failure after prolonged liver storage involves reperfusion-induced killing of sinusoidal endothelial cells and activation of Kupffer cells. Treatment of stored livers with Carolina rinse solution (CRS) prevents endothelial cell killing, reduces Kupffer cell activation, and improves graft survival. Accordingly, our aim was to evaluate the components of CRS and other agents for protection against reperfusion injury to rat livers stored 24 hr in University of Wisconsin solution. CRS virtually abolished endothelial cell killing, prevented denudation of the sinusoidal lining, and decreased structural changes in Kupffer cells indicative of activation. The only component of CRS preventing endothelial cell killing was acidic pH of 6.5. However, when pH was subsequently increased to 7.4, antioxidants (allopurinol, deferoxamine mesylate, and glutathione), vasodilators (adenosine and nicardipine), and possibly energy substrates (fructose, glucose, and insulin) partially blocked pH-dependent cell killing (pH paradox). Na+/H+ exchange inhibition, protease inhibition, and Ca(2+)-free buffer did not decrease reperfusion injury, but the amino acid glycine protected strongly. Strychnine, which binds to glycine receptors in the central nervous system, protected equally well. Protection by glycine and CRS was synergistic, virtually.

Animals↗

Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation.

Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.

Adult↗

Helicobacter pylori extract stimulates inflammatory nitric oxide production.

This study examined whether an extract of Helicobacter pylori had the ability to stimulate an inflammatory synthesis of nitric oxide, a mutagen and precursor of nitrosocompounds. Macrophages and neutrophils were prepared from rat and incubated with the Helicobacter pylori extract. L-Arginine-dependent nitric oxide production in these cells was significantly stimulated by the co-incubation with the Helicobacter pylori extract. This ability of the extract was strongly attenuated by protease digestion or heating. These results indicate that Helicobacter pylori induces production of nitric oxide and participates in development of gastritis and gastric carcinogenesis.

Animals↗