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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 253 records · Page 14Linked to original sources

Pentoxifylline in flush solution improves early lung allograft function.

BACKGROUND: Postischemic ischemia reperfusion injury is a frequent and unpredictable problem in clinical lung transplantation. Pentoxifylline (PTX) has a number of effects that could decrease reperfusion injury: reduced neutrophil adhesion to endothelium, decreased production of tumor necrosis factor, decreased platelet aggregation, and increased production of vasodilatory prostaglandins by vascular endothelium. We have demonstrated previously that PTX administered before storage and again during reperfusion reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage or reperfusion effects. METHODS: Fourteen canine left lung allotransplantations were performed. Donor lungs were flushed with modified Euro-Collins solution and stored for 24 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamic indices and arterial blood gas analysis (inspired oxygen fraction 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity was assessed. Bronchoalveolar lavage fluid was obtained from the allograft middle lobe for neutrophil counts. The animals were divided into three groups based on the timing of PTX administration. Group 1 (n = 5) animals received no PTX. Group 2 (n = 4) animals received PTX (20 mg/kg) just before reperfusion as well as continuous infusion (0.1 mg x kg-1 x min-1) during the assessment period. In group 3 (n = 5), donor lungs received PTX (200mg/L) in the flush solution only. RESULTS: Superior gas exchange was noted in the lungs receiving PTX only in the flush solution (group 3). Myeloperoxidase activity in group-3 allografts was significantly reduced. In addition, protein levels and neutrophil counts in the bronchoalveolar lavage fluid were significantly reduced in group-3 allografts. CONCLUSIONS: Pentoxifylline ameliorates lung allograft reperfusion injury when administered in the flush solution. Our data suggest that PTX will prevent graft endothelial dysfunction during 24-hour cold ischemic storage and consequently will prevent neutrophil activation and migration into lung tissue.

Analysis of Variance↗

Effect of insulin on norepinephrine overflow at peripheral sympathetic nerve endings in young spontaneously hypertensive rats.

To determine how the effect of insulin is related to the development of salt-induced hypertension, and whether a hyporesponse to insulin exists in the peripheral sympathetic nerves of a hypertensive model rat, we measured norepinephrine overflow from the periarterial nerve of isolated mesenteric arteries exposed to insulin in spontaneously hypertensive rats (SHR) as well as Wistar-Kyoto rats (WKY) fed diets that were high and low in salt. Salt loading (diet containing 8% salt for 4 weeks) accelerated the development of hypertension in young, spontaneously hypertensive rats (SHR) (157 +/- 5 mm Hg v 198 +/- 4 mm Hg, P < .01) but did not affect the blood pressure of Wistar-Kyoto rats (WKY) (102 +/- 7 mm Hg v 104 +/- 6 mm Hg, P = NS). Basal norepinephrine overflow did not differ in the SHR and WKY rats, but the overflow of norepinephrine after periarterial electrical stimulation (8 Hz 1 min.) was significantly greater in SHR (0.806 +/- 0.079 ng/g) than in WKY (0.723 +/- 0.022 ng/g; P < .01). Although insulin reduced the norepinephrine overflow by periarterial nerve stimulation in both WKY and SHR, the decrease with insulin was significantly greater in the SHR than in WKY (-18.4% +/- 4.0% v -32.0% +/- 4.6%, P < .05). The inhibitory effect of insulin on norepinephrine overflow was reduced by salt loading in SHR (-8.8% +/- 4.0%, P < .05), but not in WKY (-32.5% +/- 4.7%, P = NS). Cocaine and ouabain completely blocked the effect of insulin in all four groups. In contrast to insulin, direct stimulation of Na(+)-K+ ATPase with a high-potassium buffer (12 mmol/L) reduced NE overflow to the same extent among the four groups. These findings show that SHR have a blunted response to the suppression by insulin of norepinephrine overflow. Salt loading reduced the insulin response at peripheral sympathetic nerves of young SHR, but did not affect that of age-matched WKY. Thus, hyporeactivity to insulin may play a role in the development of salt-induced hypertension in young SHR, possibly through a reduced suppression of norepinephrine overflow from sympathetic nerve endings.

Adrenergic alpha-Antagonists↗

MS-271, a novel inhibitor of calmodulin-activated myosin light chain kinase from Streptomyces sp.--I. Isolation, structural determination and biological properties of MS-271.

A novel cyclic peptide, MS-271, was isolated from the culture broth of an actinomycete, Streptomyces sp. M-271 as an inhibitor of smooth muscle myosin light chain kinase (MLCK). MS-271 inhibited the MLCK from chicken gizzard with an IC50 value of 8 microM. MS-271 did not inhibit cyclic AMP-dependent protein kinase, protein kinase C or calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase at concentrations up to 400 microM. The primary structure of MS-271 was identical to that of siamycin I, an anti-HIV peptide isolated from a microbial source.

Adenosine Triphosphate↗

Nitroprusside ameliorates lung allograft reperfusion injury.

BACKGROUND: Nitric oxide is believed to play a critical role in the maintenance of vascular integrity through its interaction with neutrophils, platelets, and cellular components of the vessel wall. It has been reported that endogenous nitric oxide level was depressed after ischemia, reperfusion, or both. Furthermore, exogenous as well as endogenous nitric oxide decreases reperfusion-induced vascular dysfunction. We hypothesized that nitroprusside, a potent nitric oxide donor, might enhance lung preservation and reduce posttransplantation lung allograft dysfunction. METHODS: Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (inspired oxygen fraction, 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity and wet-to-dry weight ratio were assessed. Group 1 (n = 5) animals received no nitroprusside. In group 2 (n = 5), the donor lung received nitroprusside in the flush solution (10 mg/L) and recipient animals received 0.2 mg/kg just before reperfusion as well as a continuous infusion (0.11 +/- 0.01 mg.kg-1. h-1) during the assessment period. RESULTS: Superior gas exchange and hemodynamics were noted in lungs receiving nitroprusside. Although allograft myeloperoxidase activity and the total amount of fluid suctioned from the allograft were significantly reduced in group 2, protein levels in bronchoalveolar lavage fluid were not statistically different. CONCLUSIONS: Nitroprusside administration in the flush solution and during reperfusion improves lung allograft function and blood flow, and reduces pulmonary vascular resistance and myeloperoxidase activity in the transplanted lung. Nitroprusside reduces lung allograft reperfusion injury.

Animals↗

Sibling occurrence of biliary atresia and biliary dilatation.

Familial occurrence of extrahepatic biliary atresia (EHBA) or biliary dilatation has been reported; however, the genetic influences on these disorders are still obscure. The authors previously reported the occurrence of biliary dilatation and EHBA in sisters, which is extremely rare. Recently, a similar pair of sisters was treated; one had pancreaticobiliary maljunction with minimal dilatation of the common bile duct, and the other also had EHBA. The authors' investigations suggest that there may be common etiologic factors for EHBA and biliary dilatation, such as pancreaticobiliary maljunction; however, other factors are required to complete the process and cause biliary atresia.

Bile Ducts↗

Pancreaticobiliary maljunction associated with nondilatation or minimal dilatation of the common bile duct in children: diagnosis and treatment.

It is known that the etiology of congenital biliary dilatation (CBD) is closely associated with pancreaticobiliary maljunction (PBMJ). Treatment of CBD today is primary excision of the cyst followed by hepaticoenterostomy. However, PBMJ without dilatation of the biliary tract has recently been reported and its treatment is still controversial. In adults, simple cholecystectomy without biliary reconstruction is often performed, because it usually presents as an anomaly of the gallbladder. Over 30 years, we have encountered 8 patients with PBMJ without dilatation of the common bile duct in 180 pediatric cases of CBD. The presenting symptoms of these patients were those of pancreatitis i.e. abdominal pain associated with elevation of serum amylase levels. Five cases presented with jaundice or a history of pale colored stools. Endoscopic retrograde cholangiopancreatography was performed to confirm the diagnosis. Five (62.5%) of these 8 patients were found to have dilatation of the common channel, which was seen in 50 (29%) of the 172 other cases with biliary tract dilatation. Three cases (37.5%) had proven protein plugs or debris at the level of the common channel, and this was observed in 28 (16%) of the 172 other cases. It is strongly suggested that the manifestation of clinical symptoms in these patients results from stasis or obstruction at the level of the common channel. In children who present with recurrent pancreatitis, PBMJ must be suspected even if the common bile duct appears to be normal. It is difficult to resolve these anomalies without operative repair. The authors consider that radical treatment of PBMJ is required in these children to prevent serious long-term complications.

Abdominal Pain↗

Time courses of changes in cerebral blood flow and blood-brain barrier integrity by focal proton radiation in the rat.

In order to know the pathophysiological mechanisms underlying radiation brain injury, cerebral blood flow and blood-brain barrier integrity were studied using N-isopropyl-p-[123l]iodoamphetamine (IMP) and [14C]-alpha-aminoisobutyric acid (AIB), respectively, in the rat focal proton radiation model (a single dose of 30 or 60 Gy radiation with 70 MeV proton beams). One, 2, 4, and 5.5 months after irradiation, [123l]IMP and [14C]AIB were intravenously injected and uptake of IMP and AIB in the cerebral cortex, striatum, hippocampus, and thalamus was measured. Significant decreases in IMP uptake were observed in the cerebral cortex and thalamus of the irradiated side at 4 and 5.5 months after 60 Gy irradiation; the effects at 5.5 months were more prominent than those at 4 months. AIB uptake markedly increased in all the brain regions of the irradiated side at 5.5 months after 60 Gy irradiation, and at 4 months, only in the hippocampus. The results suggest that there are dose- and time-dependent responses in radiation effects and regional differences in tissue vulnerability to radiation. Proton focal radiation model appears to be a useful model for studies of radiation brain injury in small animals such as rats.

Aminoisobutyric Acids↗

Binding of anti-band 3 autoantibody to sialylated poly-N-acetyllactosaminyl sugar chains of band 3 glycoprotein on polyvinylidene difluoride membrane and sepharose gel: further evidence for anti-band 3 autoantibody binding to the sugar chains of oxidized and senescent erythrocytes.

Binding specifically of naturally occurring anti-band 3 IgG antibody isolated from human plasma was investigated in a cell-free binding system. 125I-labeled human anti-band 3 IgG specifically bound to band 3 glycoprotein and lactoferrin, a glycoprotein that has poly-N-acetyllactosamine-type sugar chains like band 3, on the polyvinylidene difluoride blotting membrane. Binding was decreased by 50-70% when band 3 and lactoferrin were pretreated with N-glycosidase F, endo-beta-galactosidase, or neuraminidase. Binding of 125I-anti-band 3 IgG to band 3-Sepharose gel was partially inhibited by band 3 oligosaccharides or lactoferrin, but was less inhibited by them after they had been treated with N-glycosidase F or endo-beta-galactosidase. A significant part of 125I-anti-band 3 IgG that bound to the band 3-Sepharose gel was released upon treatment of the gel with N-glycosidase F or endo-beta-galactosidase. IgG that binds to lactoferrin (anti-lactoferrin IgG) was isolated from normal human plasma. 125I-Anti-lactoferrin IgG bound to the band 3-Sepharose gel as effectively as to the lactoferrin-Sepharose. The antibody specifically bound to the band 3- and lactoferrin-blotted membrane depending on the poly-N-acetyllactosaminyl sugar chains of the blotted glycoproteins. The results indicate that a major part (about 70%) of anti-band 3 IgG recognizes the sialylated poly-N-acetyllactosaminyl sugar chains of band 3 and lactoferrin, and the remaining part (about 30%) of the antibody may recognize the polypeptide portion of band 3. This was supported by the observation that anti-band 3 IgG effectively bound to lactoferrin-Sepharose but 33% of the antibody did not. Anti-band 3 IgG with the carbohydrate-binding property was equally obtained whether fully denatured or barely denatured band 3 was used for isolation of anti-band 3 IgG by affinity chromatography. These results provide further evidence for our proposal that the binding sites of anti-band 3 IgG to oxidized and senescent erythrocytes reside on the locally condensed sialylated poly-N-acetyllactosaminyl sugar chains of band 3 on the cell surface.

Anion Exchange Protein 1, Erythrocyte↗

Endothelin-1 kinetics in plasma, urine, and blister fluid in burn patients.

Endothelin-1, a peptide isolated from vascular endothelial cells, facilitates the constriction of vascular smooth muscle and various pharmacological actions including vasodilation, the proliferation of smooth muscle cells and fibroblasts, and the stimulation of arachidonic acid metabolism. In this study, plasma, urine, and blister fluid endothelin-1 concentrations were determined in burn patients and changes in vasoactive substances derived from endothelial cells secondary to burns were investigated. Plasma endothelin-1 concentrations in burn patients were significantly lower than those in healthy individuals at rest. However, extremely high blister fluid endothelin-1 concentrations were observed within 30 hours of a burn. The amounts of endothelin-1 excreted in urine by burn patients over 24 hours also were higher than those in healthy individuals. The finding of high concentrations of endothelin-1 in blister fluids suggests that endothelin-1 is produced at wound regions in burn victims. Clinically, it appears that endothelin-1 is involved in circulation at the wound surface or in the healing of burns.

Adult↗

Cutaneous myiasis due to Dermatobia hominis in Japan.

A 29-year-old man with a furuncle-like lesion brought in a maggot on the next day after his first visit to our clinic. He said it moved out from the eruption spontaneously. He had previously visited Parana and Sao Paulo in Brazil before he noticed the symptom. The maggot was confirmed to be a third instar larva of Dermatobia hominis. Japanese cases of cutaneous myiasis are reviewed.

Adolescent↗

A novel dipeptidyl aminopeptidase from Pseudomonas sp. strain WO24.

An activity similar to that of dipeptidyl aminopeptidase I (DAP I) which releases dipeptide from Gly-Arg-p-nitroanilide (Gly-Arg-pNA) was detected in a Pseudomonas sp. An enzyme was isolated and purified about 400-fold by a series of column chromatographies. The enzyme, named DAP BI (DAP from bacteria, type I), was revealed to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing. The molecular mass was estimated to be 82 kDa by SDS-PAGE and 65 kDa by gel filtration, suggesting that the enzyme may be a monomer. The enzyme had an isoelectric point of 4.7. It is optimally active at pH 9.0. The Km and Vmax of the enzyme for Gly-Arg-pNA were 0.25 mM and 195 micromol/min/mg, respectively. The purified enzyme did not hydrolyze Gly-Phe-pNA, which was also a substrate for DAP I, whereas it hydrolyzed Arg-Arg-4-methoxy-beta-naphthylamide (Arg-Arg-MNA), a model substrate for DAP III. The Km and Vmax for Arg-Arg-MNA were 0.019 mM and 145 micromol/min/mg, respectively. This purified enzyme can also catalyze the removal of Asp-Arg from the N termini of angiotensins I and II. The enzyme activity was completely inhibited by Zn(II) (0.5 mM), tosyl-L-Lys-chloromethyl ketone (0.1 mM), and leupeptin (0.1 mM) and partially inhibited by Co(II) (0.5 mM) and chymostatin (0.1 mM), whereas the enzyme was not affected by general serine protease inhibitors (phenylmethylsulfonyl fluoride and diisopropylfluorophosphate) and thiol protease inhibitors. The substrate specificity, classification of catalytic site, and other enzymatic properties demonstrate that this enzyme is distinct from the previously described mammalian DAPs I and III and Saccharomyces cerevisiae DAP III. These results indicate that DAP BI may be a new type of the DAP family.

Amino Acid Sequence↗

Role of intracellular alkalinization in inhibition of acetylcholine-induced relaxation by FMLP in rat aorta.

N-formylmethionyl-leucyl-phenylalanine (FMLP), a chemotactic tripeptide, is known to cause intracellular alkalinization. Moreover, there is a specific receptor for FMLP in vascular endothelial cells but not in vascular smooth muscle cells. Because we have already reported that intracellular alkalinization inhibits acetylcholine (ACh)-induced relaxation, we examined whether FMLP alters the vasodilation of endothelial cells through intracellular alkalinization. FMLP reduced ACh-induced relaxation in aortic rings from Sprague-Dawley rats but did not affect nitroglycerin-induced relaxation. N-t-butoxycarbonyl-phenylalanyl -D-leucyl-phenylalanyl-D-leucyl-phenylalanine, a specific formyl receptor antagonist, reversed the impairment of ACh-induced relaxation, as did the protein kinase C inhibitors sphingosine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). The sodium/proton antiport inhibitor amiloride and the proton ionophore nigericin normalized the attenuated ACh-induced relaxation. FMLP-induced impairment was normalized by the phospholipase A2 inhibitor quinacrine, the cyclooxygenase inhibitor indomethacin, and the antagonists of the prostaglandin H2 and/or thromboxane A2 receptor, ONO-3708 and S-1452, respectively. Superoxide dismutase inhibited the effect of FMLP. In conclusion, FMLP attenuated ACh-induced relaxation, possibly through intracellular alkalinization. Increased production of vasoconstrictor prostaglandin(s) and superoxide may contribute to the inhibitory effect of FMLP-induced alkalinization on ACh-induced relaxation.

Acetylcholine↗

Local renin-angiotensin system in sympathetic overactivity of spontaneously hypertensive rats.

The present study was designed to clarify whether modulation of norepinephrine (NE) release by vascular angiotensin (Ang) II is involved in the increased peripheral sympathetic activity of spontaneously hypertensive rats (SHR). In the perfusion system of isolated mesenteric vascular beds, periarterial nerve stimulation (PNS)-evoked NE overflow was significantly greater in SHR than Wistar-Kyoto rats (WKY). Administration of Ang II increased PNS-induced NE overflow, which could be reversed by pretreatment with the AT1 receptor antagonist CV-11974 in both types of rats; the facilitation by Ang II was more potent in SHR. Moreover, CV-11974 by itself could attenuate PNS-evoked NE overflow, the extent of which was also significantly greater in SHR, suggesting an augmented sympatho-facilitatory effect of endogenous Ang II in SHR. Consistently, sympatho-facilitation by Ang I, which could be abolished by the angiotensin converting enzyme (ACE) inhibitor imidaprilat, was apparently greater than that of Ang II in SHR, despite no difference in WKY. These findings suggest that the increased peripheral sympathetic activity in SHR is attributed not only to the elevated sensitivity of nerve endings to Ang II but also to the increased local generation of Ang II, an effect possibly mediated by augmented vascular ACE activity.

Angiotensin II↗

An immunohistochemical study on the innervation of two peptidergic (NPY and VIP) nerves in the cerebral arterial tree and choroid plexus of the newt (Amphibia: Urodela).

The pattern of neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) innervation was investigated in the cerebral arterial tree and choroid plexus of the newt by the use of an indirect immunofluorescence technique combined with chemical sympathectomy (6-OHDA). The data presented here, in conjunction with histochemical data reported previously, showed the following characteristic features of cerebrovascular innervation in this urodelan species. (1) The cerebral arterial tree and choroid plexus had unbalanced NPY-IR and VIP-IR innervation, characterized by the absence or a markedly lesser density of VIP-IR nerves. (2) All or nearly all of the NPY-IR nerves were sympathetic in nature. (3) A few cerebral perivascular NPY-IR nerves in some individuals originated from the sympathetic NPY-IR nerve cells intrinsic to the major cerebral arteries of the anterior circulatory system. (4) Acetylcholinesterase-positive neurons lacking both NPY and VIP immunoreactivities are a major nerve type in cerebrovascular parasympathetic innervation. The preferential NPY-IR innervation of the plexus microvascular-epithelial regions must be considered in relation to its special functions, such as the regulation of microcirculation, and cerebrospinal fluid (CSF) production and transportation. CSF is vital for the movement of nutrients and metabolites in the newt brain.

Acetylcholinesterase↗

Cloning of mRNA sequences for two antibacterial peptides in a hemipteran insect, Riptortus clavatus.

Escherichia coli injection rapidly induced bactericidal activity in the hemolymph of a hemipteran insect, Riptortus clavatus. This activity reached its maximum at 9 hr after injection and thereafter declined slowly. Two types of cDNA clones involved in this response were isolated by differential screening. The predominant type encoded for an open reading frame of 678 amino acids, which consisted of fourteen tandem repeats. Each repeat was rich in charged residues and had a proline-rich region which had striking sequence similarities to proline-rich antibacterial peptides from other insect species, indicating these clones encode a multipeptide precursor of antibacterial peptides. The other type encoded for a glycine-rich peptide similar to a known antibacterial peptide as well. Northern blot analyses revealed rapid induction of mRNAs corresponding to these clones after the injection. To our knowledge, this is the first report on the mRNA sequences of antibacterial peptides of hemimetabolous insects, and the second report on the occurrence of multipeptide precursor structure in insect antibacterial peptides.

Animals↗

RES-1149-1 and -2, novel non-peptidic endothelin type B receptor antagonists produced by Aspergillus sp. I. Taxonomy of producing strain, fermentation, isolation, and physico-chemical and biological properties.

RES-1149-1 and -2, novel and non-peptidic endothelin antagonists, were isolated from the cultured broth of a fungus, Aspergillus sp. RE-1149. RES-1149-1 and -2 selectively inhibited the ET-1 binding to endothelin type B receptor (ETB receptor) with IC50 values of 1.5 microM and 20 microM, respectively. Taxonomy of producing strains, fermentation, isolation, and physico-chemical properties of RES-1149-1 and -2 are described.

Animals↗