Biomedical subjects

M Yunoki

Publications and source records attributed to M Yunoki.

At least 19 recordsLinked to original sources

PubMed2004

Heat sensitivity of a SARS-associated coronavirus introduced into plasma products.

BACKGROUND AND OBJECTIVES: Various measures to inactivate/remove viruses have been implemented for manufacturing plasma-derived products. Here, we examined the heat inactivation ability of an agent of the severe acute respiratory syndrome (SARS), SARS coronavirus (CoV). MATERIALS AND METHODS: The Frankfurt-1 strain of SARS-CoV was incorporated in manufacturing processes of several products by using samples collected immediately before liquid heat treatment at 60 degrees C. RESULTS: SARS-CoV was easily inactivated by this treatment for 60 min in all in-process samples. However, the different composition of the tested samples affected the heat sensitivity of the virus strain: the infectivity of the virus in Antithrombin III preparation still remained after heating for 30 min at 60 degrees C. CONCLUSION: If by rare chance SARS-CoV contaminates source plasma, there should be no or only minor risk of this virus infection, due to sufficient inactivation by the 60 degrees C 10 h liquid heating step, although we must pay attention to the composition used for blood product preparation.

Blood↗

PubMed2003

Heat sensitivity of human parvovirus B19.

BACKGROUND AND OBJECTIVES: To date there has been no published report on a systematic evaluation of the heat sensitivity of human parvovirus B19 (B19) and the related safety of the plasma-derived fractionated products. In this study, we examined the heat sensitivity of B19 by using the infectivity assay with cultured cells. MATERIALS AND METHODS: The heat sensitivity of B19 was examined by measuring the reduction in viral infectivity titres after heating liquid containing B19 at 60 degrees C. Viral infectivity was assayed by detection of viral antigens or viral mRNA in infected cells. As a control, canine parvovirus (CPV) was also heat-treated. RESULTS: B19 displayed quite different inactivation kinetics to CPV when both were heated in liquid at 60 degrees C. In sharp contrast to the latter, B19 was rapidly inactivated within 1 h when the virus was suspended in 5% or 25% human serum albumin solution, phosphate-buffered saline, or complete medium. However, B19 appeared to be resistant to heat inactivation in liquid containing 60% sucrose. CONCLUSIONS: The heat sensitivity of B19 in liquid was clearly different from that of CPV. Significantly, the efficiency to inactivate B19 and reduce its infectivity following heating in liquid was mainly affected by the composition of the solutions used for virus suspension.

Antigens, Viral↗

PubMed2001

Lidocaine potentiates atrial natriuretic peptide-induced relaxation of bovine tracheal smooth muscle.

The effect of lidocaine on the changes in tension and guanosine 3',5'-cyclic monophosphate (cGMP) content induced by atrial natriuretic peptide (ANP) and nitric oxide (NO) was examined in bovine tracheal smooth muscle preparations contracted with methacholine (0.3 microM). Lidocaine (10 microM) did not affect the methacholine-induced tensions, whereas 100 microM lidocaine significantly (P<0.01) attenuated methacholine-induced ones. Treatment of the tracheal preparations with lidocaine (10 and 100 microM) significantly (P<0.05) augmented the relaxant responses to ANP, whereas the same procedure did not alter the responses to sodium nitroprusside, (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR 3) or 8-bromo-cGMP. Lidocaine (100 microM) enhanced cGMP accumulation induced by ANP (0.1 microM) but not by sodium nitroprusside (0.3 microM). In contrast, mexiletine (100 microM), another class Ib antiarrhythmic, did not affect ANP- and sodium nitroprusside-induced relaxations. These results suggest that lidocaine augments ANP-induced relaxation and cGMP accumulation, probably by modulating activation mechanism of particulate guanylyl cyclase.

Animals↗

PubMed2001

Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle.

We examined the relaxant effects of N-acetylprocainamide, the major hepatic metabolite of procainamide, on bovine tracheal smooth muscle, focusing on the possible involvement of K+ channels. N-acetylprocainamide produced a concentration-dependent and full inhibition of the tension development elicited by methacholine (0.3 or 1 microM). The potency of N-acetylprocainamide in diminishing methacholine-elicited tension development was one-half of that of procainamide. By comparison, N-acetylprocainamide inhibited high-K+ (40 mM)-induced contraction more potently than procainamide though both inhibitions were largely reduced when compared to those against methacholine-induced contraction. Iberiotoxin (30 nM), Ba(2+) (1 mM) or a combination of both agents significantly attenuated the relaxant effect of N-acetylprocainamide on methacholine-induced contraction, whereas apamin (100 nM), 4-aminopyridine (300 microM), and glibenclamide (10 microM) did not affect it. These results suggest that N-acetylprocainamide, similar to procainamide, elicits tracheal smooth muscle relaxation mainly through the activation of plasma membrane K+ channels.

Acecainide↗

PubMed2001

Mexiletine inhibits pharmacological actions of salbutamol through blockade of beta2-adrenoceptors in bovine tracheal smooth muscle.

We examined the effects of mexiletine, a class Ib antiarrhythmic drug, on the changes in tension and adenosine 3',5'-cyclic monophosphate (cAMP) content induced by salbutamol and forskolin in bovine tracheal smooth muscle. Salbutamol (0.0001-1 microM) produced concentration-dependent relaxation in bovine tracheal smooth muscle contracted with methacholine (0.3 microM). Mexiletine (5-500 microM) caused the rightward shifts of concentration-response curves for the relaxant responses to salbutamol in a concentration-dependent manner. Mexiletine (5, 50 or 500 microM) did not change basal cAMP levels, whereas it concentration-dependently attenuated the salbutamol (0.1 microM)-induced cAMP accumulation. On the other hand, mexiletine (500 microM) did not change the concentration-response curves for the relaxant responses to forskolin (0.001-10 microM). Mexiletine slightly but significantly (P<0.05) increased forskolin (1 microM)-induced cAMP accumulation. In radioligand binding experiments, mexiletine concentration-dependently displaced the specific binding of [125I]cyanopindolol to beta-adrenoceptors on bovine tracheal smooth muscle membranes. By contrast, lidocaine, another class Ib antiarrhythmic drug, did not change the binding of [125I]cyanopindolol. These results demonstrate that mexiletine prevents the binding of beta2-adrenoceptor agonists to their receptors and thereby suppresses manifestation of subsequent pharmacological responses.

Adrenergic beta-Antagonists↗

PubMed2000

Involvement of K(+) channel in procainamide-induced relaxation of bovine tracheal smooth muscle.

The relaxant effect of procainamide, a class Ia antiarrhythmic agent, was examined in bovine tracheal smooth muscle. Procainamide produced concentration-dependent decreases in tension and full relaxation in the preparations contracted with methacholine (0.3 microM). By comparison, in preparations contracted with 40 mM K(+), procainamide had only slight relaxant effects. The relaxant effects of cromakalim and salbutamol on 40 mM K(+)-contracted preparations were significantly (P<0.01) smaller than those on 0.3 microM methacholine-contracted ones. On the other hand, the concentration-response relationships for quinidine, lidocaine, mexiletine and propafenone were not so dramatically different between 0.3 microM methacholine- and 40 mM K(+)-contracted preparations. Tetraethylammonium (300 microM), iberiotoxin (30 nM) and Ba(2+) (1 mM) significantly (P<0.05) attenuated the relaxant effects of procainamide on methacholine-induced contractions, whereas apamin (100 nM), 4-aminopyridine (300 microM), and glibenclamide (10 microM) did not affect them. The inhibitory effect of a combination of iberiotoxin and Ba(2+) was greater than that of iberiotoxin or Ba(2+) alone (P<0.01). These results suggest that the activation of at least two types of K(+) (maxi-K(+) and inward rectifier K(+)) channels contributes to the procainamide-induced relaxation of bovine tracheal smooth muscle.

Albuterol↗

PubMed2000

Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle.

We examined how (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632), an inhibitor of Rho-associated coiled coil-forming protein kinase (ROCK I) and Rho kinase (ROCK II), affects the relaxant responses to beta(2)-adrenoceptor agonists in bovine tracheal smooth muscle preparations precontracted with methacholine. Y-27632 (0.3-30 microM) caused a concentration-dependent attenuation of precontraction with methacholine (0.3-3 microM). Pretreatment with Y-27632 (1 microM) significantly (P<0.05) augmented salbutamol (0.3-100 nM) and terbutaline (0.3 nM-1 microM)-induced relaxations. These results suggest that the ROCK inhibitor could become a new type bronchodilator and its combination with beta(2)-adrenoceptor agonists may become a novel strategy for the long-term treatment of asthma.

Adrenergic beta-Agonists↗

PubMed2000

Lidocaine potentiates the relaxant effects of cAMP-elevating agents in bovine tracheal smooth muscle.

The effect of lidocaine on the relaxation and accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) induced by salbutamol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) was examined in bovine tracheal smooth muscle preparations precontracted with methacholine (0.3 microM). Lidocaine attenuated the methacholine-induced contraction in a concentration-dependent manner. Pretreatment of the preparations with lidocaine (100 microM) caused significant leftwards shifts of concentration/response curves for the relaxant responses to salbutamol, forskolin, and IBMX, whereas it did not change the responses to diltiazem. Similar leftwards shifts were observed when the preparations were treated with procaine (6 microM) or bupivacaine (40 microM). Lidocaine (100 microM) augmented cAMP accumulation induced by salbutamol (10 nM) and forskolin (1 microM). These results suggest that lidocaine augments the relaxant responses to cAMP-elevating agents through enhancement of cAMP accumulation.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Ischemic tolerance in the rat neocortex following hypothermic preconditioning.

OBJECT: Ischemic neuronal damage associated with neurological and other types of surgery can have severe consequences for functional recovery after surgery. Hypothermia administered during and/or after ischemia has proved to be clinically beneficial and its effects often rival or exceed those of other therapeutic strategies. In the present study the authors examined whether transient hypothermia is an effective preconditioning stimulus for inducing ischemic tolerance in the brain. METHODS: Adult rats were subjected to a 20-minute period of hypothermic preconditioning followed by an interval ranging from 6 hours to 7 days. At the end of this interval, the animals were subjected to transient focal ischemia induced by clamping one middle cerebral artery and both carotid arteries for 1 hour. The volume of cerebral infarction was assessed 1 or 7 days postischemia. In the first series of experiments, hypothermic preconditioning (28.5 degrees C) with a postconditioning interval of 1 day reduced the extent of cerebral infarction measured 1 and 7 days postischemia. In the second series, hypothermic preconditioning (31.5 degrees C) with postconditioning intervals of 6 hours, 1 day, or 2 days (but not 7 days) reduced the extent of cerebral infarction measured 1 day postischemia. Treatment with the protein synthesis inhibitor anisomycin blocked the protective effect of hypothermic preconditioning. In a final series of experiments, in vitro brain slices prepared from hypothermia-preconditioned (nonischemic) animals were shown to tolerate a hypoxic challenge better than slices prepared from unconditioned animals. CONCLUSIONS: These findings indicate that hypothermic preconditioning induces a form of delayed tolerance to focal ischemic damage. The time course over which tolerance occurs and the ability of a protein synthesis inhibitor to block tolerance suggest that increased expression of one or more gene products is necessary to establish tissue tolerance following hypothermia. The attenuation of hypoxic injury in vitro following in vivo preconditioning indicates that tolerance is due, at least in part, to direct effects on the brain neuropil. Hypothermic preconditioning could provide a relatively low-risk approach for improving surgical outcome after invasive surgery, including high-risk neurological and cardiovascular procedures.

Animals↗

PubMed1999

Hypothermia-induced ischemic tolerance.

Delayed resistance to ischemic injury can be induced by a variety of conditioning stimuli. This phenomenon, known as delayed ischemic tolerance, is initiated over several hours or a day, and can persist for up to a week or more. The present paper describes recent experiments in which transient hypothermia was used as a conditioning stimulus to induce ischemic tolerance. A brief period of hypothermia administered 6 to 48 hours prior to focal ischemia reduces subsequent cerebral infarction. Hypothermia-induced ischemic tolerance is reversed by 7 days postconditioning, and is blocked by the protein synthesis inhibitor anisomycin. Electrophysiological studies utilizing in vitro brain slices demonstrate that hypoxic damage to synaptic responses is reduced in slices prepared from hypothermia-preconditioned animals. Taken together, these findings indicate that transient hypothermia induces tolerance in the brain parenchyma, and that increased expression of one or more gene products contributes to this phenomenon. Inasmuch as hypothermia is already an approved clinical procedure for intraischemic and postischemic therapy, it is possible that hypothermia could provide a clinically useful conditioning stimulus for limiting injury elicited by anticipated periods of ischemia.

Animals↗

PubMed1999

Identification and expression of the genes encoding a reactivating factor for adenosylcobalamin-dependent glycerol dehydratase.

Adenosylcobalamin-dependent glycerol dehydratase undergoes inactivation by glycerol, the physiological substrate, during catalysis. In permeabilized cells of Klebsiella pneumoniae, the inactivated enzyme is reactivated in the presence of ATP, Mg2+, and adenosylcobalamin. We identified the two open reading frames as the genes for a reactivating factor for glycerol dehydratase and designated them gdrA and gdrB. The reactivation of the inactivated glycerol dehydratase by the gene products was confirmed in permeabilized recombinant Escherichia coli cells coexpressing GdrA and GdrB proteins with glycerol dehydratase.

Bacterial Proteins↗

PubMed1999

MR findings in degenerated ovarian leiomyoma.

Leiomyoma is one of the rarest solid tumours of the ovary. We report a case of a degenerated ovarian leiomyoma associated with pregnancy. MR findings are identical to those of degenerated uterine leiomyoma and it is difficult to differentiate between them. Ovarian leiomyoma should therefore be included in the differential diagnosis of subserosal uterine leiomyoma.

Adult↗

PubMed1998

Effects of lecithinized SOD on sequential change in SOD activity after cerebral contusion in rats.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic brain injury (TBI) in rats, we studied the SOD activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern blot analysis. As determined by the specific gravity method, the administration of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr after contusion. SOD activity, without lecithinized SOD administration, increased at the peripheral portion at 30 min after contusion, but decreased to normal level at 6 hr after TBI. By administration of lecithinized SOD, the increase of SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA increased in the core lesion, peripheral portion, and contralateral hemisphere until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD. These results support the hypothesis that superoxide anions may play an important role in the development of brain edema after TBI, and that leciyhinized SOD appears to prevent brain edema through a protective effect against superoxide anions.

Animals↗

PubMed1997

Detection of lipid peroxidation and hydroxyl radicals in brain contusion of rats.

To examine the relationship between the free radicals and brain tissue damage, we investigated the intensity of brain hydroxyl (OH) radical generation and lipid peroxidation in the rat contusion injury model. A unilateral contusion was induced by a weight-drop method. All rats were decapitated six hours after the injury, and brain samples were taken from three portions (core, peripheral, and distal) to examine the specific gravity as an indicator of brain edema, generation of OH using an electron paramagnetic resonance spectrometer (EPR), and malondialdehyde (MDA) and 4-hydroxyalkenals production. Analysis of the specific gravity revealed cerebral edema on the ipsilateral side in the injured group. The signal intensity of EPR in the core and peripheral portions in the contusion group was significantly higher than that in the distal portion of the contusion group and that of all portions in the control animals. No significant difference was observed between the core and peripheral portions of the contusion group. The MDA and 4-hydroxyalkenals production was significantly higher in the core and peripheral portions than in the distal portion of the contusion group and that of all portions of the control group. The degree of posttraumatic brain edema was closely correlated with the increase of DMPO-OH adduct, MDA, and 4-hydroxyalkenals. These results support the current concept that free radical production following traumatic brain injury may induce lipid peroxidation and may be the direct cause of edema formation.

Animals↗

PubMed1997

Effects of lecithinized SOD on contusion injury in rats.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic injury, the expression of Cu,Zn-SOD mRNA was examined after contusion in rat using Northern blotting. As determined by specific gravity, lecithinized SOD decreased brain edema. The expression of Cu,Zn-SOD mRNA increased at the core, peripheral and contralateral hemisphere of injury. These increases were then suppressed by lecithinized SOD. Our results support the hypothesis that superoxide may play an important role in edema formation after contusion, and that lecithinized SOD appears to prevent brain edema through a protective effect against superoxide injury.

Animals↗

PubMed1997

Effects of lecithinized superoxide dismutase on traumatic brain injury in rats.

Only small amounts of superoxide dismutase (SOD) are present in the extracellular space to scavenge excess amounts of superoxide anions (02-) released after traumatic brain injury (TBI). Experiments were performed in rats with cerebral contusion produced by weight-drop technique. We investigated the effects of exogenous lecithinized SOD (PC-SOD) on accumulation of 02- produced in our model, by measuring the level of SOD activity (using the NBT-reducing method) and the expression of copper, zinc-SOD (Cu, Zn-SOD) mRNA (by Northern blot analysis). As determined by tissue-specific gravity, administration of PC-SOD reduced brain edema in the periphery of the lesion 6 h after contusion. SOD activity increased in the peripheral region at 30 min after contusion, but returned to normal levels at 6 h after TBI. Administration of PC-SOD increased SOD activity up to 6 h after TBI. The expression of Cu, Zn-SOD mRNA increased in the core region, peripheral portion, and contralateral hemisphere up to 6 h after TBI, then was suppressed in all three regions by PC-SOD. Our results confirm the important role of 02- in the development of brain edema after TBI and indicate that PC-SOD diminishes brain edema through a protective effect against 02-.

Animals↗

PubMed1996

Lymph nodes in the hepatoduodenal ligament: US appearances with CT and MR correlation.

OBJECTIVE: To examine the ultrasound (US) appearances of the lymph nodes in the hepatoduodenal ligament in patients with and without hepatic diseases. PATIENTS AND METHODS: US appearances of elliptical nodules around the common hepatic artery and/or the portal vein were prospectively examined in 156 sequential patients referred for US scans. Retrospective review of CT (n=5) and MR (N=9) appearance of this structure was also performed. RESULTS: Hepatoduodenal lymph nodes were seen by US in 48 of 157 patients (31%). They were visualized in 25 of 103 patients without liver disease (24%) and 12 of 17 patients with viral hepatitis and/or cirrhosis (71%). Patients with viral hepatitis and/or cirrhosis had significantly larger hepatoduodenal nodes than patients without these diseases (P<0.01). An echogenic focus or line representing the lymphatic hilus was noted in 28 patients. The lymph nodes were hyperintense relative to the liver on T2-weighted MR images. CONCLUSION: US visualization of the lymph nodes in the hepatoduodenal ligament is not uncommon even in patients without known liver disease. Enlargement of these nodes is frequently seen in patients with viral hepatitis and/or cirrhosis.

Adult↗

PubMed1996

[Contrast enhanced CT].

Although CT is one of major diagnostic imaging methods, the role of CT in the detection and diagnosis of early carcinomas depends on the organ and character of the tumors. Because difference in attenuation between lung parenchyma and carcinomas is large, contrast enhanced CT is not effective to diagnose early lung carcinoma. However, difference in attenuation between parenchyma and tumor is small and change of the contour of the organ is not seen in many cases of small carcinomas in the liver, pancreas and kidneys, therefore helical (spiral) CT with contrast enhancement has markedly improved the diagnostic capability of small carcinomas in these organs. In the biliary tract, bladder, uterus and prostate small carcinomas can not be detected even on enhanced helical CT.

Bile Duct Neoplasms↗