Codon usage tabulated from the GenBank genetic sequence data.
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Amino Acids↗
Biomedical subjects
K Wada
Publications and source records attributed to K Wada.
Purification of an endothelin receptor from human placenta.
We have identified an endothelin (ET) binding protein on the membranes of human placenta and purified it to homogeneity. It is a polypeptide with an apparent Mol. Wt. of 40,000 and is a major protein to be labeled by cross-linking with either 125I-ET-1, -2, or -3. Binding studies with Scatchard analysis indicated the presence of a single class, high-affinity binding site with Kds of 57 pM, 480 pM and 40 nM for 125I-labeled ET-1, ET-2 and ET-3, respectively. These results suggest that the 40K protein is a major ET receptor in placenta and, most likely, can bind differentially to ET-1, ET-2 and ET-3.
Affinity Labels↗
Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders.
In order to assess the thrombin and plasmin generation in vivo in disseminated intravascular coagulation (DIC), plasma levels of thrombin-antithrombin III (ATIII) complex (TAT) and plasmin-alpha 2-antiplasmin (a2AP) complex (PAP) were measured together with standard coagulation and fibrinolytic parameters in 80 patients with DIC. Both TAT and PAP were markedly elevated in patients with DIC. When plotted by the underlying disease categories, differences in the magnitude of the elevations of these complexes were recognized among groups. Patients with acute promyelocytic leukemia (APL) had the highest PAP, the lowest TAT/PAP ratio, low a2AP, and low fibrinogen, indicating that the most excessive fibrinolysis can occur in APL. Similar profiles, although less marked, were observed in patients with other leukemias and vascular diseases. Patients with sepsis showed the highest TAT/PAP ratio and the lowest PAP with no decrease in a2AP or fibrinogen, demonstrating a relatively impaired fibrinolysis. Patients with cancer had a relatively high TAT and high TAT/PAP ratio. In addition, both TAT and PAP were markedly elevated in patients with shock. From these, it was suggested that, although laboratory manifestations in DIC are extremely variable from patient to patient, underlying disorders are, at least in part, responsible for the observed variations. Recognition of this variable activation of coagulation and fibrinolysis would be helpful for the proper management of patients with DIC.
Adolescent↗
Fibrinolysis and fibrinogenolysis in liver disease.
Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin-antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.
Antithrombin III↗
Histological features and clinical course of large regenerative nodules: evaluation of their precancerous potentiality.
Seventeen patients with cirrhosis and histologically defined, ultrasonically detected, large regenerative nodules of the liver were followed without treatment for more than 1 yr (range = 13 to 51 mo). During the follow-up period, none of the nodules were demonstrated sonographically to have enlarged. Computed tomography and/or hepatic angiography were also performed in 14 patients, but there was no evidence of malignant transformation in these lesions. None of the 17 patients showed acute elevation of serum alpha-fetoprotein levels. Furthermore, four nodules became undetectable by these imaging procedures. Follow-up biopsy performed in seven patients revealed no significant histological changes from the first biopsy sample. However, HCCs developed apart from these large regenerative nodules in four patients. These HCCs suddenly appeared and did not seem to have been derived from preexisting large regenerative nodules. From these observations, it was not possible to regard a large regenerative nodule having no cytological atypia as a high-potential premalignant lesion. Their precancerous potentiality needs to be compared with that of ordinary pseudolobules.
Angiography↗
Difference in effects of sodium fluoride and cholecystokinin on diacylglycerol accumulation and calcium increase in guinea pig gastric chief cells.
In isolated guinea pig gastric chief cells, sodium fluoride (NaF) stimulated a monophasic increase in diacylglycerol accumulation, while cholecystokinin (CCK) strongly stimulated its biphasic accumulation. NaF evoked an increase in initial Ca2+ influx rate with a slow increase in intracellular free Ca2+ concentration [( Ca2+]i), while CCK stimulated a rapid increase in [Ca2+]i followed by a late sustained phase of the [Ca2+]i increase. Lanthanum chloride (La3+) effectively blocked NaF-stimulated increase in [Ca2+]i, but it blocked only CCK-stimulated late sustained phase of [Ca2+]i increase. The effect of NaF on pepsinogen secretion was enhanced in the presence of 100 microM AlCl3. Furthermore, pertussis toxin did not affect NaF-evoked diacylglycerol accumulation at all. These results suggest that NaF may activate a pertussis-toxin insensitive guanine nucleotide regulatory protein (G protein) coupled to a signal transducing mechanism which seems to be distinct from that activated by CCK, thereby inducing increases in diacylglycerol accumulation, Ca2+ influx and pepsinogen secretion in guinea pig gastric chief cells.
Animals↗
RNA levels of neuronal nicotinic acetylcholine receptor subunits are differentially regulated in axotomized facial motoneurons: an in situ hybridization study.
In situ hybridization histochemistry using complementary RNA probes revealed that alpha 3 and beta 2 neuronal nicotinic acetylcholine receptor subunit mRNAs were expressed in 12% and 40% of facial motoneurons of the rat, respectively. The alpha 3 subunit mRNA signals disappeared in response to axotomy, whereas the beta 2 subunit mRNA signal was remarkably enhanced, suggesting that mRNA levels of receptor subunits are differentially regulated in axotomized motoneurons.
Animals↗
Giant G+C% mosaic structures of the human genome found by arrangement of GenBank human DNA sequences according to genetic positions.
To determine the overall variation in the G+C% distribution over long ranges of the human genome, DNA sequences of human genes, which were closely linked genetically or physically, were surveyed from the GenBank Data Bank. A total of 72 sequences longer than 2 kb, which were mutually linked within 500 kb, were identified. The sequences belonged to 17 linkage groups and were ordered in each group according to their genetic positions. Analyses of the G+C% distribution along the ordered sequences showed that sequences within each group almost always had similar G+C% levels, but those belonging to different groups often had different levels. Similar analyses of more distantly linked sequences (e.g., greater than 10 Mb) showed mosaic structures of G+C% distribution. These findings are consistent with predictions made from the "isochore" structures found by CsCl equilibrium centrifugation, in that the structures having homogeneous base compositions stretched over at least several hundred kilobases. A possible boundary of the giant G+C% mosaic structures was identified between X-linked G6PD and F8C.
Base Composition↗
Purification and Characterization of a Ferredoxin-NADP Oxidoreductase-Like Enzyme from Radish Root Tissues.
An enzyme able to reduce cytochrome c via ferredoxin in the presence of NADPH, was isolated, purified from radish (Raphanus sativus var acanthiformis cultivar miyashige) roots and characterized. The enzyme was purified by DEAE-cellulose, Blue-Cellulofine, Ferredoxin-Sepharose 4B, and Sephadex G-100 column chromatography. Molecular mass of the enzyme was estimated to be 33,000 and 35,000 daltons by Sephadex G-100 gel filtration and SDS-PAGE, respectively. Its absorption spectrum suggested that the enzyme contains flavin as a prosthetic group. The K(m) values for NADPH and ferredoxin were calculated to be 9.2 and 1.2 micromolar, respectively. The enzyme required NADPH and did not use NADH as an electron donor. The optimal pH was 8.4. The enzyme also catalyzed the photoreduction of NADP(+) in the spinach leaf thylakoid membranes depleted of ferredoxin and ferredoxin-NADP(+) oxidoreductase. The effect of NaCl and MgCl(2) concentration on the activity and amino acid composition of the enzyme were demonstrated. The results suggest that the enzyme is similar to ferredoxin-NADP(+) oxidoreductase from chloroplasts and cyanobacteria and is the key enzyme catalyzing the electron transport between NADPH, generated by the pentose phosphate pathway, and ferredoxin in plastids of plant heterotrophic tissues.
Journal Article↗
Neurotoxins distinguish between different neuronal nicotinic acetylcholine receptor subunit combinations.
Neuronal and muscle nicotinic acetylcholine receptor subunit combinations expressed in Xenopus oocytes were tested for sensitivity to various neurotoxins. Extensive blockade of the alpha 3 beta 2 neuronal subunit combination was achieved by 10 nM neuronal bungarotoxin. Partial blockade of the alpha 4 beta 2 neuronal and alpha 1 beta 1 gamma delta muscle subunit combinations was caused by 1,000 nM neuronal bungarotoxin. The alpha 2 beta 2 neuronal subunit combination was insensitive to 1,000 nM neuronal bungarotoxin. Nearly complete blockade of all neuronal subunit combinations resulted from incubation with 2 nM neosurugatoxin, whereas 200 nM neosurugatoxin was required for partial blockade of the alpha 1 beta 1 gamma delta muscle subunit combination. The alpha 2 beta 2 and alpha 3 beta 2 neuronal subunit combinations were partially blocked by 10,000 nM lophotoxin analog-1, whereas complete blockade of the alpha 4 beta 2 neuronal and alpha 1 beta 1 gamma delta muscle subunit combinations resulted from incubation with this concentration of lophotoxin analog-1. The alpha 1 beta 1 gamma delta muscle subunit combination was blocked by the alpha-conotoxins G1A and M1 at concentrations of 100 nM. All of the neuronal subunit combinations were insensitive to 10,000 nM of both alpha-conotoxins. Thus, neosurugatoxin and the alpha-conotoxins distinguish between muscle and neuronal subunit combinations, whereas neuronal bungarotoxin and lophotoxin analog-1 distinguish between different neuronal subunit combinations on the basis of differing alpha subunits.
Animals↗
Danazol suppresses the production of interleukin-1 beta and tumor necrosis factor by human monocytes.
The effects of estradiol (E2), progesterone (P), and danazol on the production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) by OK-432 (a streptococcal preparation)-stimulated monocytes were examined. E2 and P at physiologic concentrations enhanced IL-1 beta and TNF production by monocytes from donors with lower control levels (without steroids added) of IL-1 beta and TNF. However, E2 and P at physiologic concentrations did not affect IL-1 beta and TNF production by monocytes from donors with higher control levels of IL-1 beta and TNF. Danazol inhibited IL-1 beta and TNF production by monocytes in a dose-dependent manner from not only donors with lower control levels of IL-1 beta and TNF but also donors with higher control levels of IL-1 beta and TNF. Danazol at a concentration of 10(-6) M significantly suppressed IL-1 beta and TNF production in the presence of E2 and/or P at concentrations giving peak responses of IL-1 beta production. These findings suggest possible new mechanisms of action for danazol in the treatment of endometriosis and infertility associated with immune abnormalities.
Adult↗
Prostaglandin protects isolated guinea pig chief cells against ethanol injury via an increase in diacylglycerol.
We studied cellular processes activated by prostaglandins (PG) that are involved in the protection of gastric chief cell injury estimated in terms of dye exclusion test, release of lactate dehydrogenase (LDH), or 51Cr from prelabeled chief cells. Pretreatment of chief cells with 3 x 10(-6) M PGE2 or PGE1 at 37 degrees C and pH 7.4 for 15 min maximally reduced not only ethanol- but also taurocholic acid-caused LDH release from chief cells. PGs equipotently stimulated increases in the accumulation of diacylglycerol and cyclic AMP without elevating intracellular Ca2+ concentrations in gastric chief cells. The rank order of the potency was equal to that of PGs to reduce the injury. Pretreatment of chief cells with synthetic 1-oleoyl-2-acetyl-sn-glycerol (OAG) or 12-o-tetradecanoyl phorbol 13-acetate (TPA) reduced the injury of chief cells, while 4 alpha-phorbol 12,13-didecanoate, an inactive phorbol ester, failed to reduce the injury and 1-(5-isouinolinylsulfonyl)-2-methylpiperazine (H7) blocked the protective action of PGE2. On the other hand, forskolin and dbcAMP had no effect on ethanol-caused LDH release and diacylglycerol formation in chief cells. These results suggest that PGE2 and PGE1 possess the direct protective action against ethanol- or taurocholic acid-caused injury in chief cells, presumably through the activation of the diacylglycerol/protein kinase C signaling pathway.
Animals↗
Isolation, localization, and cloning of a kainic acid binding protein from frog brain.
Excitatory amino acids (EAA) are major neurotransmitters in the vertebrate central nervous system. EAA receptors have been divided into three major subtypes on the basis of electrophysiological and ligand binding studies: N-methyl-D-aspartate, kainate, and quisqualate receptors. To understand their molecular properties, we undertook a project aimed at isolation and cloning of these receptor subtypes. We purified a kainate binding protein (KBP) from frog brain, in which kainate binding sites are about fortyfold more abundant than in rat brain, using domoic acid affinity chromatography, and made monoclonal and polyclonal antibodies to the purified protein. These antibodies immunoprecipitate the frog KBP but not KBPs from other species. Immunocytochemical analyses show that KBP has a synaptic and extrasynaptic localization in frog optic tectum, with most labeling being extrasynaptic. The cDNA encoding frog brain KBP was isolated by screening a frog brain cDNA library with oligonucleotide probes that were based on the amino acid sequence of the purified protein. The deduced amino acid sequence of the KBP has a hydrophobic profile similar to those of other ligand-gated ion channel subunits, such as the nicotinic acetylcholine receptor, the GABAA receptor, and the glycine receptor. Frog brain KBP is very similar (36% amino acid identity to the carboxyl half) to rat brain kainate receptor, suggesting that these two proteins evolved from a common ancestor. The function of KBP in frog brain remains a major question. Preliminary results showed that Xenopus laevis oocytes injected with KBP RNA did not produce a detectable electrophysiological response when perfused with kainate. These results suggest that additional subunits may be required to form a functional receptor or that KBP is not functionally related to a neurotransmitter receptor.
Amino Acid Sequence↗
Isolation of limonin and obacunone from phellodendri cortex shorten the sleeping time induced in mice by alpha-chloralose-urethane.
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Animals↗
Pharmacological activity of angiotensin-II modified by tyrosine sulfation.
An angiotensin-II analogue with a sulfated tyrosine residue was prepared by arylsulfotransferase treatment of synthetic human angiotensin-II. Its biological activities were studied in isolated smooth muscles, and its effect on blood pressure was determined. The sulfated angiotensin-II (AII-S) was about 15-30 fold less potent than angiotensin-II (AII) for ileum contraction and gallbladder contraction. The hypertensive potency of AII-S was about 30-fold less than that of AII.
Angiotensin II↗
[Effect of teprenone and H2-receptor antagonists on phosphatidylcholine synthesis in the isolated guinea pig gastric glands].
To better understand the mechanism of phosphatidylcholine synthesis in the stomach, [3H] choline incorporation into phosphatidylcholine in response to the drugs which have been commonly used for treating the patients with gastric ulcer was examined using isolated guinea pig gastric glands. Teprenone stimulated [3H] choline incorporation into phosphatidylcholine in gastric glands, up to 146 +/- 11% of control (n = 6, P less than 0.05). On the other hand famotidine, ranitidine and cimetidine significantly decreased the incorporation to 73 +/- 8%, 72 +/- 11%, 67 +/- 11% of control, respectively (n = 6, P less than 0.05, P less than 0.05, P less than 0.05). When the glands were pulsed with [3H] choline followed by incubation in the presence of teprenone or each H2RA for 180 min to see the effects of the agents on the limiting step of the phosphatidylcholine synthesis, teprenone also significantly stimulated [3H] choline incorporation into phosphatidylcholine, but each H2RA did not affect phosphatidylcholine biosynthesis any more. Teprenone stimulated CTP:phosphocholine cytidylyltransferase (CTF) from a basal value of 0.92 +/- 0.10 to 1.69 +/- 0.39 (nmol/min/mg protein) (n = 3, P less than 0.05). These results suggest that teprenone may stimulate phosphatidylcholine biosynthesis through the activation of CTF, a late-limiting enzyme of PC biosynthesis, and H2RA may affect phosphatidylcholine synthesis by inhibiting choline transport or choline kinase in gastric glands.
Animals↗
Possibility of anti-estrogen action from estriol specific binding sites in rabbit uterus.
1. This study was designed to investigate the clomiphene or tamoxifen binding to receptor sites for estradiol-17 beta (E2R) and estriol (E3R) in the rabbit uterus. 2. Those so-called anti-estrogenic compounds tended to inhibit E2-E2R and E3-E3R bindings equally. 3. The inhibitor constant of clomiphene for E2R was approximately 3.8 x 10(-8) M at 4 degrees C and that for E3R approximately 1.8 x 10(-8) M at 4 degrees C in a given case, determined by charcoal assay. 4. It is suggested that the anti-estrogenic compounds demonstrate their effects after binding either to E2R or to E3R. 5. There were some tissue differences of the contents between E2R and E3R. For example, the uterus and the cortex contained E2R, and the pituitary E3R more than the other.
Animals↗
[Effects of ethanol on pepsinogen release from isolated guinea pig gastric chief cells].
The effects of ethanol on pepsinogen release from isolated guinea pig gastric chief cells were investigated. Ethanol, at concentrations of 300 mM to 900 mM, dose-dependently stimulated increases in pepsinogen release, initial Ca influx rate and intracellular free Ca concentration ([Ca2+]i) without affecting chief cells' viability. The increases in all parameters were inhibited by La3+ or EGTA, but not by nifedipine or verapamil. COOH-terminal octapeptide of cholecystokinin (CCK8) also stimulated increases in pepsinogen release, initial Ca influx rate and [Ca2+]i. However, the increases were dependent on not only extracellular Ca2+ but also intracellular Ca2+ mobilization. These results suggest that ethanol stimulates Ca2+ influx via the mechanism different from that of CCK8 and thereby stimulates pepsinogen release from isolated guinea pig gastric chief cells.
Animals↗