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T Taniguchi

Publications and source records attributed to T Taniguchi.

1,007 records · Page 56Linked to original sources
PubMedDate not supplied

Unique structure of murine interleukin-2 as deduced from cloned cDNAs.

Interleukin-2 (IL-2) is a lymphokine originally described as a humoral factor required for the continued proliferation of activated T-cell clones. It also seems to be involved in the mitogenic response of thymocytes, in augmenting natural killer cell activity, in the generation of cytotoxic T cells and in the induction of other lymphokines such as gamma-interferon and a B-cell growth factor (BCGF-1). More recently, there has been evidence for the involvement of IL-2 per se in the stimulation of B-cell growth (ref. 10 and T. Kishimoto and J. Vilcek, personal communications). We have reported previously the cloning and expression of a human IL-2 complementary DNA. The cDNA encodes biologically active IL-2 which would consist of 153 amino acids, including a signal sequence. Because so much of the work on IL-2 has been done in the human and mouse, we sought to obtain cDNA encoding murine IL-2, and we now report the cloning, expression and sequence analysis of murine IL-2 cDNAs. The longest cDNA insert encodes a polypeptide of 169 amino acids, containing unique repeats of a CAG sequence which would encode 12 consecutive glutamine residues within the active IL-2 molecule.

Amino Acid Sequence↗
PubMedDate not supplied

Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG.

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Reconstitution of functional receptor for human interleukin-2 in mouse cells.

Interleukin-2 (IL-2) has a key role in the antigen-specific clonal growth of T lymphocytes, by virtue of its interaction with a specific cell-surface receptor (IL-2R). The growth signal seems to be delivered by IL-2 bound to the high-affinity, but not the low-affinity, receptor. Genes encoding IL-2 and its receptor (that is, Tac-antigen) have been cloned and analysed in detail. We have now achieved cell-type-specific reconstitution of the high-affinity human IL-2R by expressing the complementary DNA cloned from normal lymphocytes. A mouse T-lymphocytic line, EL-4, expressed human IL-2R with high (dissociation constant (Kd) = 160-220 pM) and low (Kd = 2.1-2.2 nM) affinity for recombinant human IL-2, while mouse L929 cells expressed only a single class of the IL-2R with lower affinity (Kd = 34.5 nM) for the ligand. We also show that the human IL-2R expressed in EL-4 cells responds to IL-2 and mediates reversed signal transduction: growth of the EL-4 cells harbouring the IL-2R is inhibited specifically by human recombinant IL-2. The approach described here may provide a general experimental framework for elucidating the molecular basis of signal transduction mediated by specific receptor-ligand interaction.

Animals↗
PubMedDate not supplied

Relaxations of isolated rabbit coronary artery by purine derivatives: A2-adenosine receptors.

The pharmacological nature of purinoceptors in the rabbit coronary artery was investigated by comparing the extent of vasorelaxation induced by various purine derivatives, with or without amino group at C6 and with or without ribose at N9 in the purine structure. These derivatives were grouped according to structure--adenosine, inosine, adenine, and hypoxanthine analogs. The vasorelaxations produced by adenosine analogs were inhibited by aminophylline, while relaxations produced by the other three groups were unaffected. In the case of adenosine analogs, modification of amino group at C6 to secondary amine resulted in reduction of the potency of the vasorelaxing effect. The order of potency was as follows: adenosine greater than N6-(L)-phenylisopropyladenosine greater than N6-(D)-phenylisopropyladenosine greater than N6-cyclohexyl-adenosine greater than N6-(2,5-dioxo-3-pyrrolidinyl)-adenosine greater than kinetine riboside greater than N6-methyladenosine. On the other hand, the aminophylline-resistant relaxations of adenine analogs were augmented by modification of amino group at C6 to secondary or to tertiary amine. The order of potency was as follows: 6-cyclohexylaminopurine greater than 6-dimethylaminopurine greater than kinetine greater than 6-methylaminopurine adenine. Of adenosine, N6-cyclohexyladenosine, adenine, C6-cyclohexylaminopurine, and inosine, N6-cyclohexylaminopurine was the most potent phosphodiesterase inhibitor of crude enzyme prepared from rabbit aorta. From the order of potency of relaxations produced by adenosine analogs, adenosine receptors in the rabbit coronary artery seem to be of the A2-subtype. The relaxation induced by aminophylline-resistant adenine analogs may be due to activation of an unknown but specific site, since there is a structure-activity relationship in the relaxations produced by this group. Such relaxations may be linked to inhibition of phosphodiesterase in the rabbit coronary artery.

Adenine↗
PubMedDate not supplied

Heterogeneity of N-linked sugar chains of apolipoprotein B-100 in Watanabe heritable hyperlipidemic and fasting rabbits.

We have elucidated the structures of N-linked sugar chains of human apolipoprotein (apo) B-100 (Arch Biochem Biophys 1989; 273:197-205). To investigate the role of the carbohydrate moieties of apolipoprotein B-100, we determined the structures of the N-linked sugar chains of apo B-100 purified from low density lipoprotein (LDL) of a Watanabe heritable hyperlipidemic (WHHL) rabbit and compared them with those of fasting Japanese White rabbits. The N-linked oligosaccharides of apo B-100 were liberated by hydrozinolysis, followed by NaB3H4 reduction, and were fractionated by paper electrophoresis and Bio-Gel P-4 column chromatography. These consisted of one neutral fraction (N) and two acidic fractions (A1 and A2) in both WHHL and fasting rabbits. N contained high mannose type oligosaccharides consisting of Man5GlcNAc2 to Man9GlcNAc2. A1 and A2 contained monosialylated and disialylated biantennary complex type oligosaccharides, respectively. The molar ratios of N, A1, and A2 were 5:2:2 in the WHHL rabbit and 4:2:5 in fasting rabbits. The content of sialic acid residues in the WHHL rabbit was calculated to be 0.64 by taking the value of that in fasting rabbits as 1.0. These results show the heterogeneity of N-linked sugar chains of apo B-100 in WHHL and fasting rabbits and suggest the possibility that the characteristics of LDL in WHHL rabbits may be altered by making the surface charge more positive than in fasting rabbits.

Acids↗
PubMedDate not supplied

Alterations in alpha adrenergic receptors in human cerebral arteries after subarachnoid hemorrhage.

The nature of alpha adrenergic receptors in human cerebral arteries was characterized and alteration of these receptors after subarachnoid hemorrhage (SAH) was examined using a radioligand binding assay. The specific 3H-prazosin binding to human cerebral arteries was saturable and of high affinity (KD = 4.1 nM) with a Bmax of 92 fmol/mg protein. Specific 3H-yohimbine binding to these tissues was also saturable and of high affinity (KD = 23 nM) with a Bmax 250 fmol/mg protein. IC50 values of adrenergic agents for 3H-prazosin binding were as follows: prazosin, 1.2 X 10(-10) M; phentolamine, 1.3 x 10(-6) M; yohimbine, 1.2 x 10(-5); norepinephrine, 4.9 x 10(-4) M; epinephrine greater than 1 x 10(-3) M. IC50 values of adrenergic agents for 3H-yohimbine binding were as follows: phentolamine, 1.7 x 10(-7) M; yohimbine, 4.2 x 10(-7) M; prazosin, 1.9 x 10(-5) M; epinephrine, 4.4 x 10(-5) M; norepinephrine, 7.9 x 10(-4) M. KD and Bmax of 3H-prazosin and 3H-yohimbine binding after SAH were compared with findings in the non-SAH group. KD and Bmax of 3H-prazosin binding of SAH group were 6 +/- 3 nM and 90 +/- 10 fmol/mg protein, respectively (N = 3). KD and Bmax of 3H-yohimbine binding of SAH group were 42 +/- 6 nM and 460 +/- 30 fmol/mg protein, respectively (N = 5). On the other hand, KD and Bmax of 3H-prazosin binding in the non-SAH group were 4 +/- 1 nM and 90 +/- 20 fmol/mg protein, respectively (N = 5), KD and Bmax of 3H-yohimbine binding of non-SAH group were 20 +/- 5 nM and 260 +/- 30 fmol/mg protein, respectively (N = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Characterization of beta adrenergic receptors in human cerebral arteries and alteration of the receptors after subarachnoid hemorrhage.

The nature of beta adrenergic receptors in human cerebral arteries was characterized and alteration of these receptors after subarachnoid hemorrhage was examined using a radioligand binding assay. The specific 3H-dihydroalprenolol, a beta adrenergic antagonist, binding to human cerebral arteries was saturable and of high affinity (KD = 12.3 nM) with a Bmax of 790 fmol/mg protein. Ki values and Hill coefficients of adrenergic agents for 3H-dihydroalprenolol were as follows; propranolol, 4.1 X 10(-8)M, 1.01; isoproterenol, 1.7 X 10(-6)M, 0.80; epinephrine, 8.3 X 10(-6)M, 0.48; norepinephrine, 2.3 X 10(-5)M, 0.45; metoprolol, 6.8 X 10(-8)M and 7.9 X 10(-6)M, 0.62; butoxamine, 2.2 X 10(-8)M and 2.1 X 10(-6)M, 0.43. The analysis of inhibition of specific 3H-dihydroalprenolol binding by these adrenergic agents suggests that human cerebral arteries contain a high density of beta adrenergic receptors and that the receptors are classified into two types, namely beta 1 and beta 2 adrenergic receptors. The calculated beta 1/beta 2 ratio from Hofstee plots was approximately 4/6. KD and Bmax of 3H-dihydroalprenolol binding to the cerebral arteries after subarachnoid hemorrhage were compared with those of control group. KD and Bmax of 3H-dihydroalprenolol binding of subarachnoid hemorrhage group were 13.9 nM and 1140 fmol/mg protein, respectively. The calculated beta 1/beta 2 ratio was approximately 6/4. These data suggest that the density of total beta adrenergic receptors increased without any significant change in the affinity after subarachnoid hemorrhage and that the increase of beta 1 adrenergic receptors was dominant.

Acebutolol↗
PubMedDate not supplied

Characterization of muscarinic cholinergic receptors in human and dog cerebral arteries.

Various concentrations of acetylcholine (ACh) produced dose dependent relaxations of isolated, helical preparations of human cerebral arteries and these responses were blocked by atropine. The median effective concentration (EC50) of ACh was 6.1 +/- 0.2 X 10(-6)M. ACh produced dual responses in isolated dog cerebral arteries. ACh in low concentrations produced relaxation, and contraction occurred when the concentration was raised to 1 X 10(-5)M. The EC50 of ACh which produced relaxation, in dog cerebral arteries was 7.2 +/- 0.2 X 10(-7)M. Muscarinic cholinergic receptors in these arteries were analyzed directly using 3H-QNB as the ligand. The specific 3H-QNB binding to the arteries was saturable and of KD = 1.5 nM and Bmax = 93 fmol/mg protein in human cerebral arteries and KD = 0.59 nM, Bmax = 340 fmol/mg protein in dog cerebral arteries. Specific binding of 3H-QNB was displaced by muscarinic cholinergic agents. Ki values and Hill coefficients were as follows: QNB, 1.0 X 10(-9)M, 0.89; atropine, 1.1 X 10(-8)M, 0.95; ACh, 0.8 X 10(-8)M and 2.1 X 10(-6)M, 0.54; carbachol, 1.2 X 10(-7)M and 4.3 X 10(-5)M, 0.33 in human cerebral arteries and QNB, 0.55 X 10(-9)M, 0.85; atropine 0.9 X 10(-9)M, 1.00; ACh, 0.9 X 10(-9)M and 1.1 X 10(-6)M, 0.43; carbachol 6.3 X 10(-8)M and 1.1 X 10(-5)M, 0.36 in dog cerebral arteries. Endogenous choline acetyltransferase (ChAT) activity was 1.6 +/- 0.4 nmol/mg protein/hr in human cerebral arteries and 3.7 +/- 0.1 nmol/mg protein/hr in dog cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMedDate not supplied

Purification and some properties of alpha-L-fucosidase isolated from Streptococcus sanguis.

alpha-L-Fucosidase acting on naturally occurring substrates was highly purified from the growth culture of Streptococcus sanguis ATCC 10557. The molecular weight of the enzyme was approximately 120,000 and the optimal pH was at 5.5. The purified enzyme showed specificity toward the linkage of alpha-(1 leads to 2) fucosides in oligosaccharides and glycoproteins. The enzyme released L-fucose from glycoprotein in human parotid saliva.

Chromatography, Gas↗
PubMedDate not supplied

Elevated pulmonary arterial pressure in pulmonary lymphangiomyomatosis.

Pulmonary lymphangiomyomatosis (LAM) is characterized by proliferation of smooth muscles around lymphatics and bronchovascular bundles, presenting clinical manifestations of obstructive or restrictive lung disease with greatly impaired gas exchange. To date, little attention has been paid in the literature to the pathophysiology of pulmonary hypertension related to this disorder. A case of a 39-year-old woman with the characteristic clinical and histological features of pulmonary LAM is presented. She was found to have moderate pulmonary hypertension. Possible mechanisms for the development of pulmonary hypertension are discussed.

Adult↗
PubMedDate not supplied

p53 as an indicator of lymph node metastases in invasive early colorectal cancer.

We examined whether overexpression of p53 can be used as a new genetic marker to predict the presence of lymph node metastases of early invasive colorectal cancer. Forty-nine patients with primary colorectal adenocarcinomas invading to the submucosa (sm-CRC) were analyzed and 7 patients were found to have lymph node metastases. Immunostaining was used to detect the p53 overexpression; 43% of sm-CRC stained positive for p53 and all the cancer cells metastasized to lymph nodes were p53 positive. Both lymph node involvement and tumor budding were significantly more frequent in p53 positive than p53 negative tumors (p < 0.05, respectively), and multivariate analysis showed that p53 overexpression constituted a higher relative lisk for lymph node metastases of sm-CRC than either histologic type, level of sm invasion, macroscopic type, tumor budding or vascular invasion, although the difference was not significant (p = 0.086). We concluded that p53 overexpression is a useful biological marker of lymph node metastases of sm-CRC, and that p53 negative status may be an indicator for limited surgery, such as local excision of sm-CRC.

Adenocarcinoma↗
PubMedDate not supplied

Pathological changes in chicks inoculated with the picornavirus "avian nephritis virus".

One-day-old chicks were inoculated intraperitoneally with a newly isolated picornavirus. The inoculated chicks showed no clinical signs until 28 days postinoculation (PI), but discoloration of the kidneys was recognized from 7 to 21 days PI at autopsy. Histologically, focal lesions were observed in the cortex of the kidneys from 3 to 21 days PI. The lesions were characterized by interstitial lymphocytic infiltration and degeneration of epithelial cells of the proximal convoluted tubules. The degenerated cells contained acidophilic granules in their cytoplasm. Electron-microscope examination of the cytoplasm revealed electron-dense amorphous areas, phagosomal areas with viral particles, and isolated crystal arrays of the virus particles, 23 to 30 nm in size. Granular antigen was also detected by fluorescent-antibody technique in the cells.

Animals↗
PubMedDate not supplied

Pathogenicity and distribution of egg-drop syndrome-1976 virus (JPA-1) in inoculated laying hens.

Rhode Island Red laying hens that lacked hemagglutination-inhibition antibody were inoculated orally with the JPA-1 strain of adenovirus isolated from a flock affected with egg-drop syndrome-1976 in Japan and observed for 80 days. Inoculated hens laid abnormal eggs, such as shell-less, soft-shelled, and cracked eggs and those with loss of pigmentation, from 8 days postinoculation (PI). Fifteen out of 16 hens laid abnormal eggs. Egg-production rte fell from 94% to 50% between 13 and 16 days PI. When the abnormal eggs were excluded, egg production was 17%; then it recoverd slowly, reaching 67% by the end of the experiment. The virus was recovered from various organs of inoculated hens from 3 to 7 days PI. Fluorescent antigens of the virus were observed in the epithelial cells and desquamated cells from the epithelium of the uterus and isthmus 10 and 14 days PI.

Adenoviridae Infections↗
PubMedDate not supplied

Susceptibility of chickens to avian nephritis virus at various inoculation routes and ages.

Factors that influence the response of chickens to avian nephritis virus (ANV) were studied. Day-old specific-pathogen-free chicks were inoculated with the G-4260 strain of ANV by oral, subcutaneous, intratracheal, intramuscular, and intracerebral routes at a dose of 10(5.0) plaque-forming units (PFUs) per chick. Inoculation induced only nephritis, and contact infection ANV occurred very easily. When 1-, 14-, 28-, 56-, and 300-day-old chickens were inoculated orally with 10(5.0) PFUs of the virus, the day-old chicks appeared to be most susceptible; histopathological responses to the virus became weak as chicks aged. The serological response of 28-day-old chickens to ANV was stronger that those of other groups. Pathologically, the adult chickens hardly responded to the virus, but they produced antibodies against the virus.

Age Factors↗
PubMedDate not supplied

Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats.

Clarithromycin and its metabolites have been examined for their abilities to induce specific form(s) of cytochrome P-450 and metabolite complex formation in rats. Pretreatment of rats with clarithromycin,N-demethyl clarithromycin, clarithromycin N-oxide, and decladinosyl clarithromycin resulted in 48-75% decreases in the amount of 2C11 and 100-600% increases in the amount of 3A1. Clarithromycin and N-demethyl clarithromycin, but not decladinosyl clarithromycin, produced a metabolite complex with cytochrome P-450 in vivo. Activities of testosterone 2 beta- and 6 beta-hydroxylases were increased by administration of clarithromycin and N-demethyl clarithromycin when these activities were measured in the presence of ferricyanide, but not significant induction was observed when measured in the absence of ferricyanide. Clarithromycin N-oxide treatment resulted in the increase in hydroxylation of testosterone not only at the 2 beta- and 6 beta-positions (430 and 190%, respectively), but also at 7 alpha-position (60%), regardless of the presence or absence of ferricyanide. In vitro experiments with hepatic microsomes of dexamethasone-pretreated rats indicated that the metabolites that were modified at the tertiary amino group more efficiently produced the metabolite complex with cytochrome P-450 compared with the parent compound. In contrast, decladinosyl and hydroxylated metabolites had similar or lower capacities for metabolite complex formation than did the parent compound. Clarithromycin and its N-modified metabolites were able to induce 3A1 and form a metabolite complex with cytochrome P-450 in vivo in varying extents. Decladinosyl clarithromycin has a weak inducibility of 3A1 and did not form a metabolite complex with cytochrome P-450 in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Effect of chronic cardiac pacing on cross-bridge activation rate in the human left ventricle].

Our active cross-bridge model has theoretically established that the cross-bridge activation rate constant of the left ventricular myocardium (Ka), which may correspond to the rate constant for the binding of Ca2+ with troponin C, can be approximately expressed as a simple formula: Ka = 3/electromechanical systole (sec-1). To determine whether this constant has the potential to be used as a clinical index of cardiac adrenergic tone, we investigated the chronic effect of cardiac pacing on the value of Ka in 15 subjects with a pacemaker in full pacing rhythm. The value of Ka (7.10 +/- 0.50 vs 6.62 +/- 0.39 sec-1, p < 0.05) and that of Ka corrected for heart rate (Kac) (7.63 +/- 0.50 vs 6.60 +/- 0.41 sec-1, p < 0.01) were both decreased significantly at one month or more after permanent pacemaker implantation. Another eight subjects were investigated to evaluate the effect on Kac of acute left bundle branch block due to intermittent right ventricular pacing. Intermittent pacing did not cause a significant change of the Kac value (7.46 +/- 0.43 vs 7.29 +/- 0.39 sec-1). The decrease of Kac during chronic cardiac pacing might reflect reduced cardiac adrenergic activity, since acute left bundle branch block due to intermittent right ventricular pacing did not affect this parameter.

Adult↗