Effects of FR167653 on pulmonary ischemia-reperfusion injury in rats: a preliminary study.
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Animals↗
Biomedical subjects
S Satoh
Publications and source records attributed to S Satoh.
Single center analysis of non-heart-beating cadaveric donors.
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Brain Death↗
Dehydroepiandrosterone (DHEA) ameliorates the insulin sensitivity in older rats.
To evaluate whether dehydroepiandrosterone (DHEA) ameliorates the decreased insulin sensitivity in older rats, hyperinsulinemic euglycemic clamp studies were performed in rats of various age groups previously treated with DHEA. The glucose metabolic clearance rate (MCR) of the control rats showed a gradual decline with the advancing ages (MCR = 13.05 - 0.027*age (days), r2=0.683, p < 0.01, n = 18). The glucose MCR of the DHEA-treated rats also showed a gradual decline with the aging process (MCR = 12.67 - 0.011*age (days), r2=0.429, p < 0.01, n = 18). However, the MCR of the DHEA-treated rats were significantly higher than that of control rats. As glucose MCR is a parameter which indicates the insulin sensitivity in various tissues, especially in muscles and body composition, was not changed after the injection of DHEA, DHEA is considered to work on muscles to increase insulin sensitivity.
Aging↗
Pharmacological characterization of a nonpeptide bradykinin B2 receptor antagonist, FR165649, and agonist, FR190997.
1. The nonpeptide bradykinin (BK) B2 receptor antagonist, FR165649 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N-methylamino]benzyloxy]-2-methylquinoline), and agonist, FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridyl methoxy)quinoline) have been identified. These compounds have a common chemical structure, and the 2-pyridylmethoxy group is the only structural difference between them. 2. Both FR165649 and FR190997 displaced [3H]-BK binding to B2 receptors in guinea-pig ileum membranes, with an IC50 of 4.7 x 10(-10) M and 1.5 x 10(-9) M, respectively. They also displaced [3H]-BK binding to B2 receptors in human lung fibroblast IMR-90 cells, with an IC50 of 1.6 x 10(-9) M and 9.8 x 10(-10) M, respectively. 3. In guinea-pig isolated ileum-preparations, FR165649 had no agonistic effect on contraction and caused parallel rightward shifts of the concentration-response curves to BK on contraction. Analysis of the data produced a nominal pA2 value of 9.2+/-0.1 (n=5) and a slope of 1.4+/-0.1 (n=5). On the other hand, FR190997 induced concentration-dependent contraction of guinea-pig ilea with a pD2 of 7.9+/-0.2 and the contraction was inhibited by a specific peptide bradykinin B2 receptor antagonist, Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]BK) in a non-competitive manner. 4. In IMR-90 cells, FR165649 had no agonistic effect on phosphatidyl inositol (PI) hydrolysis and caused parallel rightward shifts (approximately 200 fold shift at 10(-7) M) of the concentration-response curves to BK on PI hydrolysis. FR190997 induced concentration-dependent PI hydrolysis in IMR-90 cells with a pD2 of 8.4+/-0.1, and this effect was inhibited by Hoe 140. 5. These results indicate that FR165649 and FR190997 are, respectively, a potent bradykinin B2 receptor antagonist and agonist, and that the agonistic activity depends on the small part of the nonpeptide ligand. FR165649 and FR190997 may be useful tools for studying the relationship between ligands and receptors.
Animals↗
Early detection of AML1/MTG8 fusion mRNA by RT-PCR in the bone marrow cells from a patient with isolated granulocytic sarcoma.
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Adult↗
Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene.
KAI1 is a potential metastatic suppressor gene for prostate cancer. We found by Northern blot analysis that six of ten (60%) gastric and colon cancer cell lines exhibited undetectable or very low expression level of KAI1 mRNA. The effects of KAI1 on the adhesion, motility and invasiveness of colon cancer cells was therefore investigated by using two kinds of stable transfectants, i.e., antisense transfectants of BM314 cells whose KAI1 mRNA expression was suppressed by transfer of antisense KAI1 cDNA and sense transfectants of DLD-1 cells with the enhanced KAI1 mRNA by sense cDNA transfer. The following results were obtained: (1) KAI1 gene expression had no significant effect on in vitro cell growth rate of colon cancer BM314 and DLD-1 cells; (2) Cell aggregation assay showed that KAI1 enhanced the Ca++-independent aggregatability of those colon cancer cells; (3) It was revealed by cell motility and invasion assays that KAI1 suppressed both the motility and in vitro invasiveness of those cells and (4) Furthermore, both the binding to fibronectin and the migration on fibronectin-coated plates of those cells were inhibited by KAI1 expression. These suggest that reduced KAI1 gene expression may contribute to the invasiveness and metastatic ability of colon cancer cells.
Antigens, CD↗
Pemphigus with features of both vulgaris and foliaceus variants, associated with antibodies to 160 and 130 kDa antigens.
We report an unusual variant of pemphigus in a 44-year-old man. He presented with scaly and crusted erosions associated with pruritic vesicles and erythema mainly on the chest, abdomen, back and face. Histology showed acantholysis with neutrophilic spongiosis in the granular layer and subcorneal region of the epidermis. Intercellular IgG in the epidermis was positive on direct immunofluorescence. Indirect immunofluorescence showed intercellular antibodies at a titre of 1 : 2 in the suprabasal epidermis. Circulating autoantibodies to 130 kDa and 160 kDa antigens were detected in the patient's serum by immunoblot analysis using epidermal extracts. These two antibodies eluted from individual nitrocellulose membranes reacted with the intercellular space in the epidermis on indirect immunofluorescence. This observation suggests that these antibodies correspond to desmogleins 3 and 1, respectively. The clinical symptoms almost completely disappeared after 28 days treatment with oral prednisolone (30 mg/day), leaving brown pigmented flecks on the lesional sites. These findings suggest that this patient's pemphigus has features of both the vulgaris and foliaceus variants, with antibodies against desmogleins 3 and 1.
Adult↗
Succinylated collagen crosslinked by thermal treatment for coating vascular prostheses.
Vascular prostheses coated with collagen carefully prepared to avoid contamination were tested to see if it could induce endothelial cell lining throughout the graft surface in a natural way. The collagen fibers were succinylated. Hydrogel produced with the succinylated collagen was used for the sealant to reduce the amount of solid substance. To avoid contamination and the side effects of chemical reagents, the collagen thermally crosslinked under sterile conditions. A suspension of the collagen fibers was enmeshed in the interstices of Dacron fibers of fabric prostheses, which were then thermally crosslinked at 130 degrees C for 20 h. The prostheses were porous when the collagen fiber network was dry. Under wet conditions, however, the water permeability of the grafts was reduced to 0.1 ml/min from the 1,250 ml/min of the original prostheses. Three weeks after implantation in the abdominal aortas of dogs, 81.2 +/- 11% of the luminal surface was macroscopically thrombus free, and 56 +/- 14% was endothelialized. More than 95% of the coated collagen had been absorbed. Numerous fibroblasts had migrated into the graft walls, and capillary blood vessels had infiltrated the inside of the graft walls without foreign body reaction. In the controls, thrombus free areas averaged 9.0 +/- 5%, and endothelialized areas averaged 5.2 +/- 4%. Many giant cells, plasma cells, and lymphocytes had migrated into the graft walls, but no fibroblasts. These results suggest that rapid endothelialization is possible when clean collagen is used.
Animals↗
Choice, isolation, and preparation of cells for bioartificial vascular grafts.
Preparation of cells and tissues for bioartificial vascular grafts is discussed from the viewpoint of tissue engineering. In general, a neointima is not formed on vascular prostheses except at the anastomotic sites. Graft surfaces do not heal and are covered with fresh thrombi for a long period of time after implantation. The delayed healing is, so to speak, an intractable ulcer of the vascular wall. To overcome this problem, we have developed a tissue fragment transplantation method. We consider that neointima formation of vascular prostheses after implantation is a product of tissue engineering in vivo. Therefore, 3 essential elements for tissue engineering, i.e., cells, extracellular matrices, and cytokines, are required for neointima formation. Synthetic vascular prostheses lack one or more of these elements. In this study we demonstrated a standard healing process of fabric vascular prostheses and an antithrombogenic polymer graft using animal models. Then we showed the tissue fragment transplantation method using venous tissues, adipose tissues, and bone marrow. This method provided the 3 essential elements to the prostheses. To allow these elements to be actively engaged in neointima formation, we treated cells and tissues as clumps without enzymatic digestion. We also took advantage of the in vivo environment. With the results we demonstrate our way of thinking in relation to bioartificial vascular grafts.
Adipose Tissue↗
Root-specific expression of genes for novel glycine-rich proteins cloned by use of an antiserum against xylem sap proteins of cucumber.
Candidate cDNAs for xylem sap proteins (XSPs) were isolated by screening of a cucumber cDNA library prepared from poly(A)+ RNA of cucumber roots with an antiserum raised against the XSPs of cucumber. The patterns of expression of corresponding transcripts and the sequences of the cDNAs were examined. Two cDNAs with a glycine-rich domain in each deduced amino acid sequence and whose transcripts were expressed predominantly in roots were selected for further analysis. Both cDNAs encoded proteins with a putative signal sequence, with similar non-glycine-rich domains at the amino terminal of the encoded polypeptides. The corresponding mRNAs accumulated concurrently with the formation of adventitious roots from cuttings of cucumber hypocotyls and the development of vascular tissues, and strong expression of the mRNAs was detected in the root-hair zone of tap roots. These data suggest that the production of the two novel glycine-rich proteins, which are putative XSPs, might be associated with the functions of the vascular tissues in roots.
Amino Acid Sequence↗
Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy.
OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.
Adolescent↗
Effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker, on adrenal catecholamine secretion in anesthetized dogs.
We investigated the effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker possessing blocking actions on N-type and L-type voltage-dependent Ca2+ channels (VDCCs), in comparison with the L-type VDCC blocker nifedipine, on adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. Ca2+ channel blockers and cholinergic agonists were infused and injected, respectively, into the adrenal gland through the phrenicoabdominal artery. Cilnidipine (0.3-3 microg/min) inhibited increases in both epinephrine (EPI) and norepinephrine (NE) output induced by SNS (2 Hz), ACh (1.5 microg), and DMPP (0.2 microg). However, cilnidipine inhibited increase in NE output induced by muscarine (1 microg) without affecting increase in EPI output. Nifedipine (0.3-3 microg/min) inhibited the ACh- and DMPP-induced increases in EPI and NE output without affecting the SNS- and muscarine-induced increases in EPI and NE output. From these results, it seems likely that the inhibition by cilnidipine of the SNS-induced EPI and NE secretion and of the muscarine-induced NE secretion is related to its blocking action on N-type VDCCs.
Acetylcholine↗
Nd:YAG laser photodisruption for preretinal hemorrhage due to retinal macroaneurysm.
PURPOSE: To document the clinical course of Nd:YAG laser photodisruption for eyes with preretinal hemorrhage following rupture of a retinal macroaneurysm. METHODS: We reviewed six eyes of five patients with preretinal hemorrhage due to retinal macroaneurysm that received Nd:YAG laser photodisruption. Nd:YAG laser created a focal opening in the anterior surface of the preretinal hemorrhage, permitting the blood to enter the vitreous cavity where it would be absorbed more rapidly. RESULTS: Three eyes showed both subhyaloid hemorrhage, which was resorbed without treatment within 2 months, and hemorrhagic detachment of the internal limiting membrane (ILM), which required Nd:YAG laser photodisruption. All eyes showed disappearance of the preretinal hemorrhage and improvement of vision within 1 week of Nd:YAG laser photodisruption. Visual recovery was less prominent in eyes associated with subretinal macular hemorrhage. CONCLUSION: Preretinal hemorrhage due to a ruptured retinal macroaneurysm could be dispersed into the vitreous cavity with Nd:YAG laser photodisruption. It should be considered in the decision of Nd:YAG laser photodisruption that the visual increment may be limited in eyes that also have subretinal hemorrhage in the macula and that the hemorrhage beneath the ILM tends to remain longer than the subhyaloid hemorrhage.
Aged↗
Charge collection and radiation hardness of a SOI microdosimeter for medical and space applications.
The first results obtained using a SOI device for microdosimetry applications are presented. Microbeam and broadbeam spectroscopy methods are used for determining minority carrier lifetime and radiation damage constants. A spectroscopy model is presented which includes the majority of effects that impact spectral resolution. Charge collection statistics were found to substantially affect spectral resolution. Lateral diffusion effects significantly complicate charge collection.
Alpha Particles↗
Effects of zaprinast on renal nerve stimulation-induced anti-natriuresis in anaesthetized dogs.
1. We examined whether zaprinast, a putative cGMP-specific phosphodiesterase inhibitor, affects neural control of renal function in pentobarbital-anaesthetized dogs. 2. Renal nerve stimulation (1 Hz, 1 ms duration) reduced urine flow rate, urinary Na+ excretion (UNaV) and fractional excretion of Na+ (FENa) with little change in either renal blood flow (RBF) or glomerular filtration rate (GFR). 3. Intrarenal arterial infusion of zaprinast (10 and 100 micrograms/kg per min) increased basal urine flow rate, UNaV and FENa but not RBF or GFR. Zaprinast infusion (100 micrograms/kg per min) also increased renal venous plasma cGMP concentration and urinary cGMP excretion. 4. Renal nerve stimulation-induced reductions in UNaV and FENa were attenuated during zaprinast infusion, whereas the reduction in urine flow rate was resistant to zaprinast. 5. Renal nerve stimulation increased the renal venous plasma noradrenaline concentration and renal noradrenaline efflux, which remained unaffected during infusion of zaprinast (100 micrograms/kg per min). 6. The results of the present study suggest that zaprinast induces natriuresis and counteracts adrenergically induced antinatriuresis by acting on renal tubular sites in the dog kidney in vivo.
3',5'-Cyclic-GMP Phosphodiesterases↗
Pancreatic exocrine dysfunction associated with mitochondrial tRNA(Leu)(UUR) mutation.
We report on pancreatic exocrine dysfunction in families that have the mitochondrial tRNA(Leu)(UUR) gene mutation. These families exhibited maternally inherited diabetes mellitus (DM) and an A to G substitution at nt 3243 of the mitochondrial tRNA(Leu)(UUR) gene (A3243G mutation). Pancreatic necropsy samples from one proband showed accumulation of degenerated mitochondria in pancreatic acinar cells. Pancreatic exocrine dysfunction was recognised by a functional pancreatic study. This study indicates that exocrine pancreatic dysfunction may be associated with the A3243G mutation.
4-Aminobenzoic Acid↗
Role of K+ channels in adrenal catecholamine secretion in anesthetized dogs.
We examined the role of K+ channels in the secretion of adrenal catecholamine (CA) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. K+ channel blockers and the cholinergic agonists were infused and injected, respectively, into the adrenal gland. The voltage-dependent K+ channel (KA type) blocker mast cell degranulating (MCD) peptide infusion (10-100 ng/min) enhanced increases in CA output induced by SNS (1-3 Hz), but it did not affect increases in CA output induced by ACh (0.75-3 micrograms), DMPP (0.1-0.4 microgram), or muscarine (0.5-2 micrograms). The small-conductance Ca(2+)-activated K+ (SKCa) channel blocker scyllatoxin infusion (10-100 ng/min) enhanced the ACh-, DMPP-, and muscarine-induced increases in CA output, but it did not affect the SNS-induced increases in CA output. These results suggest that KA channels may play an inhibitory role in the regulation of adrenal CA secretion in response to SNS and that SKCa channels may play the same role in the secretion in response to exogenously applied cholinergic agonists.
Acetylcholine↗
Role of nitric oxide in adrenal catecholamine secretion in anesthetized dogs.
We examined the role of nitric oxide (NO) in adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS) and exogenous acetylcholine (ACh) in anesthetized dogs. The NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e (NOC 7), and ACh were administered intra-arterially into the adrenal gland. The increases in catecholamine output induced by ACh (0.75-3 microgram) were enhanced by L-NAME (0.1-1 mg/min) and inhibited by NOC 7 (0.2-2 microgram/min). Inhibition by NOC 7 (2 microgram/min) was observed during treatment with L-NAME (1 mg/min). The increases in catecholamine output induced by SNS (1-2 Hz) were inhibited by L-NAME and by NOC 7. No inhibitory effect of NOC 7 was observed during treatment with L-NAME. These results suggest that NO may play an inhibitory role in the regulation of adrenal catecholamine secretion in response to exogenous ACh.
Acetylcholine↗