Biomedical subjects

Y Takei

Publications and source records attributed to Y Takei.

At least 37 records · Page 2Linked to original sources

PubMed2001

Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin.

BACKGROUND: Studies with gut sterilization and Kupffer cell inactivation support the hypothesis that endotoxin and Kupffer cells are involved in mechanisms of alcohol-induced liver injury. Recently, we found that Kupffer cells isolated from rats treated only once with ethanol were sensitized to endotoxin 24 hr later. Moreover, we established a new, simple animal model of ethanol hepatotoxicity based on Kupffer cell sensitization. The purpose of this study was to determine the mechanisms by which alcohol sensitizes Kupffer cells to lipopolysaccharide (LPS). METHODS: Female Wistar rats were given ethanol (5 g/kg body weight) once every 24 hr intragastrically, and ethanol concentration, ethanol elimination, and portal vein endotoxin were measured. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated 24 hr after ethanol administration in vivo and were cultured in RPMI 1640 with 10% fetal bovine serum. After the addition of LPS, intracellular Ca2+ was measured by using a microspectrofluorometer with the fluorescent indicator fura-2, and tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western analysis. RESULTS: Ethanol levels exhibited a cyclic pattern in ethanol-treated rats. Similar results were obtained in groups given ethanol and antibiotics for 4 weeks. Rates of alcohol elimination were around 3.5 mmol/kg/hr in control rats. After 4 weeks of ethanol treatment with or without antibiotics, elimination rates were not changed. Translocation of horseradish peroxidase was increased about 3-fold in gut segments by treatment with ethanol. This increase was not altered by treatment with antibiotics. Moreover, portal vein endotoxin levels were increased from nearly undetectable levels to 80 pg/ml in plasma of rats treated with ethanol. As expected, this increase was prevented (<20 pg/ml) by antibiotics. In isolated Kupffer cells from rats treated with ethanol for 4 weeks, CD14, LPS-induced intracellular Ca2+, and TNF-alpha all were increased. These phenomena were blocked by antibiotics. CONCLUSIONS: Kupffer cells isolated from rats treated with ethanol for 4 weeks exhibit sensitization to LPS. It is likely that increased permeability of the gut is a prominent event that leads to alcoholic liver injury.

Animals↗

PubMed2001

Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation.

OBJECTIVE: Adult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease were reported in Japan and therefore, this disease has not been well recognised outside this country. The detailed clinical pictures of the patients with type II citrullinaemia are reported and their outcomes after liver transplantation referred to. METHODS: Ten patients with this disease were evaluated. Seven of them underwent liver transplants using a graft obtained from a healthy family member. RESULTS: There were six men and four women; the age of onset of encephalopathy ranged from 17 to 51 years. The initial symptom in nine patients was sudden onset disturbance of consciousness, and one patient had long been regarded as having a chronic progressive psychotic illness. High concentrations of plasma citrulline and ammonia were commonly seen on admission. Although brain CT or MRI lacked any consistent findings, the EEG was abnormal in all patients, showing diffuse slow waves. Additionally, in five patients chronic pancreatitis preceded the onset of encephalopathy. After liver transplantation the metabolic abnormalities, including abnormal plasma concentrations of citrulline and ammonia, were immediately corrected and all neuropsychic symptoms soon disappeared, except for impaired cognitive function in one patient. Six out of these seven patients returned to their previous social lives, including work. CONCLUSIONS: The clinical concept of adult onset type II citrullinaemia coincides well with the range of hepatic encephalopathy, and liver transplantation is a very promising therapeutic approach.

Adolescent↗

PubMed2001

Enhanced expression and release of C-type natriuretic peptide in freshwater eels.

C-type natriuretic peptide (CNP) is recognized as a paracrine factor acting locally in the brain and periphery. To assess the role of CNP in teleost fish, a cDNA encoding a CNP precursor was initially cloned from the eel brain. CNP message subsequently detected by ribonuclease protection assay, using the cDNA as probe, was most abundant in the brain followed by liver, gut, gills, and heart. Expression was generally higher in freshwater (FW) than in seawater (SW) eels, but not in the brain. Plasma CNP concentration measured by a newly developed homologous radioimmunoassay for eel CNP was higher in FW than in SW eels. The CNP concentration was also higher in the heart of FW eels but not in the brain. These results show that CNP is abundantly synthesized in peripheral tissues of FW eels and secreted constitutively into the circulation. Therefore, CNP is a circulating hormone as well as a paracrine factor in eels. Together with our previous demonstration that CNP-specific receptor expression is enhanced in FW eels, it appears that CNP is a hormone important for FW adaptation. Because atrial NP (ANP) promotes SW adaptation in eels, CNP and ANP, despite high sequence identity, appear to have opposite effects on environmental adaptation of the euryhaline fish.

Amino Acid Sequence↗

PubMed2001

Antidipsogenic effects of eel bradykinins in the eel Anguilla japonica.

A peptide with bradykinin (BK)-like immunoreactivity was isolated from an incubate of heat-denatured eel plasma with porcine pancreatic kallikrein. The purified peptide had the following amino acid sequence: Arg-Arg-Pro-Pro-Gly-Ser-Trp-Pro-Leu-Arg. This decapeptide, named eel [Arg(0)]BK, was identical to two previously identified BK homologs from cod and trout. High conservation of the BK sequence among distant teleost species suggests an important function in this vertebrate group. Bolus intra-arterial injections of eel [Arg(0)]BK, BK, and [Arg(0)]-des-Arg(9)-BK (1-10 nmol/kg) caused significant (P < 0.05) inhibition of drinking in seawater-adapted eels. The potency of the inhibition was ranked in the following order: [Arg(0)]BK > [Arg(0)]-des-Arg(9)-BK = BK. The BK peptides also produced an immediate, transient increase followed by a sustained increase in arterial blood pressure and an initial decrease followed by an increase in heart rate. Strong tachyphylaxis occurred for the cardiovascular effect but not for the antidipsogenic effect. The order of the potency of the cardiovascular actions, [Arg(0)]BK > BK > [Arg(0)]-des-Arg(9)-BK, was different from that of the antidipsogenic action. Slow infusions of eel [Arg(0)]BK in the dose range 1-1,000 pmol x kg(-1) x min(-1) produced concentration-dependent inhibition of drinking without changes in arterial pressure, plasma osmolality, and hematocrit. At the infusion rate of >100 pmol x kg(-1) x min(-1), plasma concentrations of angiotensin II, a potent dipsogenic hormone in eels, increased, suggesting an interaction of the kallikrein-kinin and renin-angiotensin systems. In mammals, BK is dipsogenic and vasodepressor, so that our data demonstrate opposite effects on fluid and cardiovascular regulation of BK in the eel and suggest a new physiological role for the kallikrein-kinin system in teleost fish.

Angiotensin II↗

PubMed2001

Micrometastatic p53-positive cells in the lymph nodes of early stage epithelial ovarian cancer: prognostic significance.

We used immunohistochemical staining of p53 protein to detect micrometastasis in regional lymph nodes that were judged tumor-free by conventional histopathological methods in 58 patients with stage I or II (pT1 or 2, N0) epithelial ovarian cancer. Overexpression of p53 protein in the primary lesions of ovarian cancer was observed in 31 patients (53%), and p53 protein-positive cells were detected in the regional lymph nodes (micrometastasis-positive) in 19 of 31 patients with p53 protein overexpression (61%). In patients with micrometastasis, the prognosis was significantly poorer than that in those without micrometastasis (p < 0.05). Detection of micrometastasis of the regional lymph nodes of ovarian cancer by immunohistochemical staining of p53 protein may be useful in predicting the prognosis of patients with stage I or II epithelial ovarian cancer.

Adult↗

PubMed2001

Relative potency of three homologous natriuretic peptides (ANP, CNP and VNP) in eel osmoregulation.

Evidence has accumulated that atrial natriuretic peptide (ANP) plays important roles in sea-water adaptation in eels. However, the roles of the other two natriuretic peptides (CNP and VNP) in osmoregulation have not been examined yet. In the present study, the effects of homologous ANP, CNP and VNP were compared on plasma Na+ concentration (an indicator of plasma osmolality), hematocrit (an approximate indicator of blood volume) and drinking rate in freshwater- and seawater-adapted eels. In seawater eels, ANP and VNP, but not CNP, infused at 5 pmol/kg/min decreased plasma Na+ concentration and drinking rate and increased hematocrit. In freshwater eels, ANP and VNP failed to decrease plasma Na+ concentration but increased hematocrit to the same extent as in seawater eels. Inhibition of drinking was not detectable in freshwater eels because of little drinking before NP infusions. These results show that the effects of NPs on plasma Na+ concentration, drinking rate and hematocrit are mediated by NPR-A, since only ANP and VNP that bind with higher affinity to NPR-A are effective in seawater eels. The mechanisms of regulation of plasma Na+ concentration and hematocrit are unknown, but NPR-A is present in the responsible tissues for regulation of hematocrit in both freshwater and seawater eels. However, NPR-A may be absent in the tissues of freshwater eels that are responsible for regulation of plasma Na+ concentration.

Adaptation, Physiological↗

PubMed2001

Rhabdomyolysis triggered by an asthmatic attack in a patient with McArdle disease.

We describe a patient with McArdle disease who developed rhabdomyolysis triggered by a bronchial asthmatic attack. A 64-year-old man had chronic pulmonary emphysema with asthma, and an asthmatic attack led to severe rhabdomyolysis that required continuous hemodiafiltration. After 2 years, a physical examination revealed atrophy of the extremities compared with previous examinations, especially of the intercostal muscles. During that time, he suffered two severe bronchial asthmatic attacks. His serum level of creatinine kinase remained between 4,000 and 7,000 IU/l when he did not suffer from asthmatic attacks and rhabdomyolysis had abated. Therefore, we suspected that his recent muscle atrophy was caused by asthmatic attacks, and discussed the possibility of his respiratory muscle weakness due to McArdle disease in relation to his severe bronchial asthmatic attacks as well as chronic obstructive pulmonary disease.

Asthma↗

PubMed2001

Recurrent cerebral embolism in a familial amyloid polyneuropathy patient who received partial liver transplantation from a living donor.

Cerebral embolism in relation to cardiac amyloidosis has not been widely noted. A 47-year-old woman who had been suffering from familial amyloid polyneuropathy (FAP) for 7 years was treated with partial liver transplantation from a living donor and her early postoperative course was uneventful. During the 391st to 613th postoperative day she experienced recurrent cerebral infarctions, but clinical examinations revealed no disorders capable of producing cerebral embolism. At autopsy splenic infarction and intracardiac thrombi adhering to the mitral valve and left atrium were found, and these areas showed severe amyloid deposition. Amyloid heart is considered to be one possible cause of systemic embolism.

Amyloid Neuropathies↗

PubMed2001

Hypothalamic encephalitis with bradycardia.

A 74-year-old man developed fever, somnolence, hyponatremia, and life-threatening sinus bradycardia for three weeks. He showed a slight elevation of lymphocyte count and protein level in the cerebrospinal fluid. A brain CT scan revealed a diffuse low density area around the hypothalamus which was identified as a high intensity signal by flair MR imaging. Marked sinus bradycardia developed with no abnormality in the echocardiograph or cardiac enzymes. Over the next 6 weeks he became alert and normal sinus rhythm resumed. The results of endocrine tests were compatible with hypothalamic insufficiency with partial hypopituitarism and the syndrome of inappropriate secretion of ADH.

Aged↗

PubMed2001

Various cooking methods and the flavonoid content in onion.

Onion is a major source of flavonoids and is cooked in various ways in the world. The major flavonoids in onion are two quercetin glycosides, quercetin 4'-O-beta-glucoside (Q4'G) and quercetin 3,4'-O-beta-diglucosides (Q3,4'G), which are recognized as bioactive substances that are good for our health. We have investigated the effect of cooking procedures on the content of antioxidants. We selected quercetin conjugates, total phenol compounds, and ascorbic acid to estimate the amount of flavonoid ingestion from onion. We examined the following cooking methods: boiling, frying with oil and butter, and microwave cooking. Various cooking methods do not consider the degradation of quercetin conjugates when cooking onion. Microwave cooking without water better retains flavonoids and ascorbic acid. Frying does not affect flavonoid intake. The boiling of onion leads to about 30% loss of quercetin glycosides, which transfers to the boiling water. At that time, the effect of additives on the quercetin conjugates is different according to the compounds. The hydrolysis of quercetin glycosides for daily cooking might occur with the addition of seasonings such as glutamic acid. Additional ferrous ions accelerated the loss of flavonoids.

Antioxidants↗

PubMed2001

[Post-genome challenges against inflammatory bowel diseases].

Advancement of genome analysis might give great impact to the treatment of inflammatory bowel diseases(IBD). IBD patients are treated by sulfadrugs, steroids and anti-immune drugs. For difficult cases, leukocytapheresis, beclomethasone dipropionate, anti-TNF therapy, anti-LTB4 therapy and other new methods are applied. Developing epoch-making drugs will be achieved by finding new molecular targets. Histologic identification of dysplasia is important in the surveillance of long-standing ulcerative colitis. The molecular diagnosis is required for the distinction of dysplasia from the regenerative inflammatory changes. P53 immunostaining have been proved useful. Various molecular targets will be taken into discussion as additional procedures. Recent genome analysis have revealed some genetic factors contribute to pathogenesis of IBD, which are HLA, IL4, MUC3, IBD1 locus, IBD2 locus and so on. More information about genes concerning IBD will be provided by analyzing dense SNP map using DNA tip. They will open the way to the tailored therapy.

Biomarkers↗

PubMed2001

Comparative molecular biology of natriuretic peptide receptors.

Analysis of the mammalian natriuretic peptide system has established the presence of three types of receptors with distinct structural and functional features and tissue distributions. To clarify the physiological role of each subtype, we studied the natriuretic peptide system in animals with specialized anatomical and physiological features. In this review, following a brief description of the comparative and evolutionary aspects of the ligands, we will analyze the structure and distribution of natriuretic peptide receptors in lower vertebrates, as well as those of rats with essential and salt-sensitive hypertension, and discuss the evolutionary aspects of the natriuretic peptide systems in mammals and fishes. Emphasis is placed on our series of studies with eel receptors that revealed (i) interesting variations in the pattern of intra- and inter-molecular disulfide bonding; (ii) dense chondrocyte localization of NPR-C, which opened a new field of study for natriuretic peptides and bone metabolism; and (iii) the presence of a new receptor subtype, NPR-D, which is abundant in the brain and a member of the receptor subfamily with a short cytoplasmic C-terminal tail.

Amino Acid Sequence↗

PubMed2001

Long-term alcohol exposure changes sensitivity of rat Kupffer cells to lipopolysaccharide.

BACKGROUND: Chronic ethanol treatment enhances Kupffer cell sensitivity to lipopolysaccharide (LPS). In this model, CD14 in Kupffer cells was increased significantly 4 weeks after ethanol. Moreover, it was shown that prostaglandin E2 produced by activated Kupffer cells participated in the mechanism of ethanol-induced fatty liver. This study was designed to elucidate the temporal effect of chronic ethanol exposure on Kupffer cell sensitization to LPS. METHODS: Rats were given ethanol every 24 hr intragastrically for up to 12 weeks, and Kupffer cells were isolated 24 hr after the final ethanol administration and cultured in RPMI 1640 with 10% fetal bovine serum. After addition of LPS to Kupffer cells, intracellular calcium ([Ca2+]i) was measured. RESULTS: CD14 in Kupffer cells was increased approximately 2-fold, and then it decreased and returned to control levels. The LPS-induced increases in [Ca2+]i and tumor necrosis factor-alpha by Kupffer cells were also increased approximately 3-fold over control values, but they also returned to control levels. Triglyceride content increased with the duration of chronic ethanol treatment. At 8 weeks, prostaglandin E2 produced by Kupffer cells increased approximately 3-fold over control values and triglycerides by approximately 4-fold before gradually decreasing to basal levels. After 12 weeks of ethanol exposure, LPS-induced increases in [Ca2+]i and tumor necrosis factor-alpha production were only approximately 50% as high as peak levels at 4 weeks. Liver triglyceride content at 12 weeks was reduced significantly compared with values at 8 weeks. CONCLUSIONS: Kupffer cells at the early stage of chronic ethanol exposure exhibited sensitization to LPS, but this sensitivity was blunted later. This correlated with triglyceride accumulation in the liver. These data indicate that long-term alcohol exposure changes the sensitivity of rat Kupffer cells to LPS but that the magnitude of the effect is time dependent.

Animals↗

PubMed2001

[Placement of the inferior vena cava filter proximal to the renal vein in a patient with left-sided inferior vena cava complicated by pulmonary embolism: a case report].

A 55-year-old man was admitted to our hospital complaining of dyspnea and chest pain. Transthoracic echocardiography showed dilation of the right ventricle. Chest computed tomography with contrast medium showed multiple emboli in the pulmonary arteries. Venography of the lower extremities showed multiple thrombi in the right popliteal vein and the presence of left-sided vena cava. This unusual case of left-sided vena cava was complicated by deep vein thrombosis due to hemostasis. A Greenfield filter was placed in the vena cava proximal to the right renal vein in a right internal jugular vein approach.

Humans↗

PubMed2000

Multiplicity, structures, and endocrine and exocrine natures of eel fucose-binding lectins.

Lectins, a group of proteins that bind to cell surface carbohydrates and play important roles in innate immunity, are widely used experimentally to distinguish cell types and to induce cell proliferation. Eel serum lectins have been useful as anti-H hemagglutinins and also in lectin histochemistry as fucose-binding lectins (fucolectins), but their structures have not been determined. Here we report the primary structures and the sites of synthesis of eel fucolectins. Eel serum fucolectins were separated by two-dimensional gel electrophoresis and sequenced. cDNA cloning, based on the amino acid sequence information, and Northern blot analysis indicated that 1) the fucose-binding lectins are secretory proteins and have unique structures among the lectins, exhibiting only weak similarities to frog pentraxin, horseshoe crab tachylectin-4, and fly fw protein; 2) there are at least seven closely related members; and 3) their messages are abundantly expressed in the liver and in significant levels in the gill and intestine. The lectin-producing hepatic cells were identified by immunostaining; in the gill, exocrine mucous cells were stained, suggesting that serum fucolectins derive from the liver. Using primary culture of eel hepatocytes, the message levels were shown to be increased by lipopolysaccharide, suggesting a role for fucolectins in host defense. SDS-polyacrylamide gel electrophoresis analysis showed that eel fucolectins have a SDS-resistant tetrameric structure consisting of two disulfide-linked dimers.

Amino Acid Sequence↗

PubMed2000

Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes.

Tau and MAP1B are the main members of neuronal microtubule-associated proteins (MAPs), the functions of which have remained obscure because of a putative functional redundancy (Harada, A., K. Oguchi, S. Okabe, J. Kuno, S. Terada, T. Ohshima, R. Sato-Yoshitake, Y. Takei, T. Noda, and N. Hirokawa. 1994. Nature. 369:488-491; Takei, Y., S. Kondo, A. Harada, S. Inomata, T. Noda, and N. Hirokawa. 1997. J. Cell Biol. 137:1615-1626). To unmask the role of these proteins, we generated double-knockout mice with disrupted tau and map1b genes and compared their phenotypes with those of single-knockout mice. In the analysis of mice with a genetic background of predominantly C57Bl/6J, a hypoplastic commissural axon tract and disorganized neuronal layering were observed in the brains of the tau+/+map1b-/- mice. These phenotypes are markedly more severe in tau-/-map1b-/- double mutants, indicating that tau and MAP1B act in a synergistic fashion. Primary cultures of hippocampal neurons from tau-/-map1b-/- mice showed inhibited axonal elongation. In these cells, a generation of new axons via bundling of microtubules at the neck of the growth cones appeared to be disturbed. Cultured cerebellar neurons from tau-/-map1b-/- mice showed delayed neuronal migration concomitant with suppressed neurite elongation. These findings indicate the cooperative functions of tau and MAP1B in vivo in axonal elongation and neuronal migration as regulators of microtubule organization.

Aging↗

PubMed2000

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage.

The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.

Amino Acid Sequence↗

PubMed2000

Viability of Q-wave infarcted myocardium with restored positive and persistent negative T waves after optimal revascularization compared with dobutamine stress echocardiography.

To clarify the clinical difference in viability of myocardium with negative and positive T waves in Q-wave anterior or anteroseptal myocardial infarction, we performed low-dose dobutamine stress echocardiography in 17 patients with negative T waves and in 13 patients with positive T waves with optimal revascularization of infarct-related arteries in the chronic phase of infarction. At baseline the wall motion score (WMS) of the negative and positive T groups was 25.8 +/- 3.0 and 22.3 +/- 2.2 points (p <0.05), respectively. At peak stress WMS in each group was 27.2 +/- 4.2 and 19.8 +/- 2.4 points (p <0.0001), respectively. With dobutamine stress WMS in the positive T group was more decreased than that of the negative T group (p <0.0001). We conclude that the restored positive T waves in Q-wave myocardial infarction indicate a significantly greater amount of viable myocardium than the negative T waves, showing better regional wall motion improvement with low-dose dobutamine stress.

Aged↗