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Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 649 records · Page 36Linked to original sources

Contribution by bradykinin to the natriuretic response to the angiotensin converting enzyme inhibitor ramiprilat in spontaneously hypertensive rats.

It is well documented that angiotensin converting enzyme inhibitors decrease blood pressure, which is associated with natriuresis in humans and certain animal models of hypertension. However, it is not clear whether these beneficial effects are due solely to blockade of angiotensin-II production and/or also involves any contribution by kinins. The present study was performed in Inactin (5-ethyl-5-(1-methylpropyl)-2-thio-barbiturate sodium)-anesthetized spontaneously hypertensive rats aged 10-13 wks to examine the relative influence of the angiotensin receptor antagonist losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1- [(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl] imidazole potassium salt) and the bradykinin receptor 2 antagonist HOE 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8] bradykinin) on renal and hemodynamic responses to the angiotensin converting enzyme inhibitor ramiprilat. We found that ramiprilat (1 mg/kg, i.v.) caused sustained reduction in mean blood pressure, marked increases in urine output and urinary sodium excretion without alteration in glomerular filtration rate. In a separate group of animals, it was found that losartan (1 mg/kg, i.v.) decreased blood pressure to a similar degree as ramiprilat and the magnitude of blood pressure fall seen following the combined administration of ramiprilat and losartan was similar to that caused by either compound alone. However, the increase in urinary sodium excretion seen following losartan administration was significantly smaller than that following ramiprilat or ramiprilat plus losartan.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗

The development of a small bowel volvulus in the early postoperative period following a distal gastrectomy: report of a case.

A 51-year-old Japanese man who underwent a standard distal gastrectomy for cancer of the stomach developed abdominal pain when oral intake was commenced on the 6th postoperative day after an uneventful postoperative course. Complete obstruction of the jejunum led to a sudden deterioration in his general condition and a laparotomy was performed, revealing counterclockwise rotation of the mesenterium. The necrotic portion of the small intestine was removed, while 10 cm of the upper jejunum and 100 cm of the terminal ileum were preserved. His second postoperative course was uneventful apart from the development of "intestinal hurry," which is now under medical control 9 months after his second laparotomy.

Adult↗

Primary chylopericardium.

To evaluate the surgical treatment of primary chylopericardium, 2 cases of primary chylopericardium are described and previous case reports are reviewed. Enhanced computed tomography combined with lymphangiography is a very reliable diagnostic tool for identifying abnormalities of the thoracic duct and its lymphatic channels connecting to the pericardium. When the course of the thoracic duct was identified exactly, ligation and resection of the thoracic duct with establishment of a pericardial window proved to be the most effective surgical procedure. Because the thoracic duct and the pericardium can be exposed easily, left thoracotomy seems to be the most preferable approach for the operation.

Adolescent↗

New composite graft repair for patients with and without Marfan's syndrome.

We developed a new composite graft repair technique to prevent the complications associated with Bentall-type procedures. The technique consists of the creation of a double proximal suture line and direct coronary artery implantation as a Carrel patch without wrapping. We retrospectively compared the outcome in patients with Marfan's syndrome (n = 16) and other disorders (aortitis, 11 patients; degenerative disease, 18 patients) who had undergone this procedure. In patients with Marfan's syndrome, there was one hospital death and six deaths during long-term follow-up. Among patients with Takayasu's arteritis, there was one hospital death and one late death. There was one late death in the patients with degenerative disease. No mortality or complications directly related to the surgical procedure occurred in any group. The high late mortality in patients with Marfan's syndrome was primarily due to distal aortic dissection or rupture. Thus, the major complications associated with Bentall-type procedures can be prevented through the use of our new composite graft technique. However, close serial follow-up, careful blood pressure control, and early detection and treatment of distal recurrence are mandatory in the postoperative management of patients with Marfan's syndrome.

Adult↗

Effect of interleukin-1 beta on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats.

Airway responsiveness (AR) to inhaled acetylcholine and bradykinin and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred male Brown-Norway rats actively sensitized to ovalbumin and later given 500 U interleukin-1 beta (IL-1 beta) intratracheally. We examined animals 14 to 21 days after initial sensitization at 18 to 24 hours after the intratracheal administration of IL-1 beta. We evaluated AR to acetylcholine as -log PC200, which is -log10 transformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increase in lung resistance. BALF was examined as an index of inflammatory changes within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals that were given IL-1 beta demonstrated a significant increase of AR to bradykinin at 18 to 24 hours and a significant increase of neutrophil counts in BALF, which was already observed by 4 to 6 hours. There was a significant correlation between AR to bradykinin and neutrophil counts in BALF in all animals (r = 0.644; p < 0.0005). We conclude that intratracheal administration of IL-1 beta induces the inflammatory changes, which are characterized by an increase in neutrophil counts in BALF, and increased AR to bradykinin, and that active sensitization per se does not potentiate the effect of IL-1 beta on AR to acetylcholine or bradykinin or on airway inflammation.

Acetylcholine↗

Discrimination by added ions of ligands at ionotropic excitatory amino acid receptors insensitive to N-methyl-D-aspartate in rat brain using membrane binding techniques.

The addition of potassium thiocyanate almost quadrupled binding of [3H]DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) to an AMPA-sensitive subclass of brain excitatory amino acid receptors in rat brain synaptic membranes, treated with Triton X-100. Among several ligands tested, quisqualic acid (QA) was the most potent displacer of [3H]AMPA binding in the absence of added SCN- ions, followed by AMPA, 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), glutamic (Glu) and kainic (KA) acids in a rank order of decreasing potency. The addition of SCN- ions was effective in significantly reducing the potencies of antagonists such as DNQX and CNQX, without affecting those of agonists including QA, AMPA, Glu and KA. On the other, the addition of Ca2+ ions significantly inhibited [3H]KA binding in a concentration-dependent manner at concentrations of above 2.5 mM. Calcium ions were also effective in significantly potentiating potencies to displace [3H]KA binding of antagonists such as DNQX and CNQX, with concomitant reduction of those of agonists including KA, QA and Glu. However, N-methyl-D-aspartic acid (NMDA) did not affect binding of both radioligands at concentrations of below 0.1 mM. These results suggest that both SCN- and Ca2+ ions may be useful to discriminate agonists and antagonists among a variety of displacers of ligand binding to the non-NMDA receptors in the brain.

Animals↗

Effects of low-power laser irradiation on multiple unit discharges induced by noxious stimuli in the anesthetized rabbit.

This study discusses the effects of low-power laser irradiation upon multiple unit discharges within a peripheral nerve that were induced by a noxious stimulation in anesthetized rabbits. Responding to a pinch stimulation of plantar skin, transitory increase of neuronal discharges was induced in the sural nerve. This was reduced within a minute, and persistent increases, which continued during a period of the stimulation, occurred. These increases became significantly smaller than the control value during a low-power laser irradiation that was applied to the exposed sural nerve distal to the recording site. These results suggested an inhibitory effect of low-power laser irradiation on the impulse conduction within a peripheral nerve. Possible analgesic effects of low-power irradiation are discussed.

Animals↗

Expression of octopus rhodopsin in Escherichia coli.

Apoproteins, having various molecular weights, of octopus rhodopsin (oRh, 455 amino acids), which is a typical transmembrane protein, were expressed in Escherichia coli with an inducible expression system using promoter phi 10 of the T7 phage. Fifteen synthetic genes (212-1,365 bp) for oRh (1) were cloned downstream from gene 10 of the T7 phage (846 bp), under the control of promoter phi 10. An expression vector for mature oRh containing no extra peptide resulting from gene 10 was also constructed. Protein productivities were mainly evaluated by ELISA using monoclonal antibodies. The expression level in E. coli of the fused oRh genes varied between 1 and 200 mg/liter of the culture medium (from approximately 0.25 to 50% of the total cell protein, respectively), depending on the fused oRh genes. The amount of mature oRh protein expressed in E. coli was approximately 0.1 to 1 mg/liter. Hydropathy index analysis of gene products showed a significant negative correlation (rho = - 0.63) between expression level of oRh gene products in E. coli and their hydrophobic characteristics. Wavelength shifting of the absorption maximum by exogenous addition of retinal to apoprotein similar to that of authentic oRh was demonstrated in the membrane fraction of E. coli expressing mature opsin.

Animals↗

The role of MRSA (methicillin-resistant Staphylococcus aureus) adherence and colonization in the upper respiratory tract of geriatric patients in nosocomial pulmonary infections.

The mechanism of nosocomial respiratory infections caused by MRSA (methicillin-resistant Staphylococcus aureus) in geriatric patients was investigated. Seriously ill patients (SIP) undergoing naso-gastric tube feeding or intravenous hyperalimentation and moderately ill patients (MIP) who were orally fed, were examined for their colonization and infection by Staphylococcus aureus (S. aureus) in the respiratory tract. Colonization of MRSA in the upper respiratory tract in SIP was from six to ten times higher than that in MIP and was associated with a high incidence of MRSA pulmonary infections. In vitro S. aureus adherence to nasal or oropharyngeal cells demonstrated that bacteria binding to nasal cells was higher, which probably can be interpreted as an elevated occurrence of S. aureus colonization in the nasal cavity than in the throat. The binding activity of MRSA was not superior to that of MSSA (methicillin-sensitive S. aureus). Though MRSA binding to the nasal cells from SIP was not higher than those from MIP, MRSA colonization in the upper respiratory tract was more frequently seen in SIP (P < 0.01). A higher incidence of total infectious episodes (P < 0.02-0.001) and more frequent use of antibiotics (P < 0.02-0.001), which were potent against MSSA might be the basis for selection of MRSA in these patients. In fact, the rate of MRSA colonization on the skin (pressure sores) was also higher in SIP (P < 0.01). A low nutritional state in SIP (P < 0.01-0.02) might also be associated with MRSA colonization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Attenuation of adenylate cyclase-induced increases in renal sodium excretion by the dopamine D-2 receptor agonist SK&F 89124.

1. Although the existence of D-2 receptor binding sites in kidney has been identified, their functional significance in terms of influencing renal sodium excretion is not clear. In the present study we have examined the renal effects of a selective D-2 receptor agonist, SK&F 89124, in anaesthetized rats. 2. Intravenous infusion of SK&F 89124 (0.3, 1 and 3 micrograms kg-1 min-1 respectively) produced dose-dependent decreases in mean arterial blood pressure, heart rate and renal blood flow without causing any significant changes in urine output, urinary sodium excretion, renal vascular resistance or glomerular filtration rate. The changes in blood pressure, heart rate and renal blood flow caused by SK&F 89124 were abolished by a selective D-2 receptor antagonist, domperidone (50 micrograms kg-1 i.v. bolus; 10 micrograms kg-1 min-1). 3; Treatment with 3-isobutyl-1-methylxanthine (IBMX, 1 mg kg-1 bolus i.v.) or forskolin (200 micrograms kg-1 bolus i.v.) produced increases in heart rate, urine output and urinary sodium excretion, but there was no change in mean blood pressure. The natriuretic and diuretic response, but not tachycardiac response to IBMX or forskolin, was attenuated by SK&F 89124 (0.3 micrograms kg-1 min-1). 4. These results suggest that the selective D-2 receptor agonist, SK&F 89124, produced a significant decrease in blood pressure and heart rate via prejunctional D-2 receptor-mediated inhibition of noradrenaline release from postganglionic sympathetic nerve terminals. Although activation of renal tubular D-2 receptors had no significant effect on renal excretory function under basal conditions, it is likely that these receptors may exert an opposing effect on cAMP-mediated increases in renal sodium and water excretion.

1-Methyl-3-isobutylxanthine↗

E-selectin and vascular cell adhesion molecule-1 as critical adhesion molecules for infiltration of T lymphocytes and eosinophils in atopic dermatitis.

To study the temporal and spatial relationship between infiltrating T-cell subsets or eosinophils and cell adhesion molecules on endothelial cells in skin lesions of atopic dermatitis (AD), we undertook immunohistochemical analysis using monoclonal antibodies against surface markers of T cells, eosinophil granule proteins and cell adhesion molecules. Predominant mononuclear cells in acute and chronic skin lesions were CD3, CD4 and CD45RO positive helper-inducer/memory T cells. Their number was significantly and strongly correlated with the intensity of E-selectin expression. Eosinophils and deposition of eosinophil-derived granule proteins such as eosinophil cationic protein (ECP), major basic protein (MBP) and eosinophil peroxidase (EPO) were found constantly in acute lesions and only occasionally in chronic lesions. The total number of immunoreactive eosinophils and deposits of MBP, EPO and ECP were significantly and strongly correlated with the staining intensity of VCAM-1. In chronic lesions significant reduction of VCAM-1 expression paralleled occasional infiltration of eosinophils. Our results demonstrate the possibility that E-selectin and VCAM-1 are the critical adhesion molecules for trafficking of memory T cells and eosinophils, respectively, into skin lesion of AD. Persistent expression of the adhesion molecules may be related to prolongation of the skin lesion in AD.

Adolescent↗

Inactivation of the macrolide antibiotics erythromycin, midecamycin, and rokitamycin by pathogenic Nocardia species.

A survey of five Nocardia spp. with respect to susceptibility towards three macrolides (erythromycin, rokitamycin, and midecamycin) showed that the Nocardia spp. have different susceptibility profiles. Most of the resistance was due to the inactivation of the macrolides by phosphorylation, glycosylation, reduction, deacylation, or a combination thereof.

Biotransformation↗

Circadian variation in fibrinolytic activity in patients with variant angina.

BACKGROUND: Coronary artery spasm induces activation of the coagulation system. Turnover and maintenance of thrombus depend not only on formation but also on lysis. The relation between coronary spasm and fibrinolytic system has not been elucidated. OBJECTIVE: To examine whether there is impairment of or a circadian variation in fibrinolytic activity in patients with variant angina. METHODS: Plasminogen activator inhibitor (PAI) activity and concentrations of tissue plasminogen activator (t-PA) antigen were measured in venous plasma samples taken at 2200, 0600, and 1400 and 24 h Holter tapes were recorded in 15 patients with variant angina, 12 patients with stable exertional angina, and 12 controls. RESULTS: There were significant circadian variations in PAI activity and t-PA antigen with peak values at 0600 in all three groups. Mean (SEM) PAI activity (IU/ml) at 2200, 0600, and 1400 was 6.1 (1.1), 11.0 (1.3), and 4.4 (0.6) in the variant angina group; 1.8 (0.7), 5.6 (1.1), and 1.2 (0.3) in the stable exertional angina group; and 1.1 (0.5), 4.5 (0.8), and 0.7 (0.3) in the control group. Furthermore, both plasma PAI activity and t-PA antigen concentrations were significantly higher in the variant angina group than in the stable exertional angina group and the control group at each sampling time. CONCLUSIONS: In patients with variant angina there was a circadian variation in fibrinolytic activity, which was lowest in the early morning, and impaired fibrinolytic activity particularly in the early morning, when attacks of angina occur most frequently.

Aged↗

Role of cyclooxygenase and 5-lipoxygenase metabolites, platelet-activating factor and 5-hydroxytryptamine in allergen-induced airway responses in the brown Norway rat.

We determined the effects of selective inhibition of arachidonic acid metabolism via the cyclooxygenase and 5'-lipoxygenase pathways using flurbiprofen and BWA4C, respectively, of 5-hydroxytryptamine (5-HT) using methysergide and of platelet-activating factor (PAF) using WEB 2086 on the airway responses to ovalbumin (OA) aerosol in OA-sensitized Brown Norway rats. Twenty-one days after intraperitoneal injection of OA, rats were exposed to a 1% OA or saline aerosol. Only methysergide (10 mg/kg i.p.; 3 doses over 24 h) provided significant protection of the immediate response to OA. The increase in airway responsiveness to acetylcholine after OA exposure was not significantly altered by methysergide, flurbiprofen (10 mg/kg i.p.), BWA4C (50 mg/kg i.p.) and WEB 2086 (50 mg/kg i.p.) all given over 24 h prior to OA challenge. In addition, there was no effect on the increased recovery of eosinophils and lymphocytes in bronchoalveolar lavage fluid at 24 h. We conclude that 5-HT is an important mediator of the acute response to OA, but that 5-HT, lipoxygenase and cyclooxygenase products and PAF are unlikely to be involved in OA-induced airway hyperresponsiveness and inflammation in the Brown Norway rat.

Allergens↗

Prevention of arterial reocclusion after thrombolysis with activated protein C. Comparison with heparin in a canine model of coronary artery thrombosis.

BACKGROUND: Reocclusion of recanalized coronary arteries often limits the efficacy of coronary thrombolytic therapy in patients with acute myocardial infarction. Activated protein C (APC) is an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the effect of APC on thrombolysis with recombinant tissue-type plasminogen activator (rTPA) was studied in a canine model of coronary artery thrombosis. METHODS AND RESULTS: Continuous artery flow monitoring in the left anterior descending coronary artery of 30 anesthetized adult beagles was performed by a magnetic flowmeter. Localized thrombosis was produced in the left anterior descending coronary artery and administration of rTPA (alteplase, 0.45 mg/kg IV) was done for 30 minutes. The dogs were randomly assigned to receive one of the following intravenous adjunctive therapies: (1) control group (n = 10): human albumin at a rate of 0.83 mL/min; (2) APC group (n = 10): human plasma-derived APC (0.6 mg/kg) with human albumin as a vehicle at a rate of 0.83 mL/min; and (3) heparin group (n = 10): heparin (200 U/kg) with saline at a rate of 0.83 mL/min. Each adjunctive therapy was started simultaneously with rTPA and lasted for 60 minutes. Coronary recanalization occurred in all dogs of each adjunctive treatment group in 19.1 +/- 1.9 minutes (mean +/- SEM). In a 120-minute observation after the termination of rTPA, reocclusion developed in all the dogs in the control and heparin groups but in only 3 of the 10 dogs in the APC group (P < .002 versus control and heparin). Time from recanalization to reocclusion (minutes, mean +/- SEM) was prolonged in the APC group (103.2 +/- 14.2) as compared with the control (10.2 +/- 2.3, P < .001) and heparin (30.3 +/- 11.8, P < .002) groups. Activated partial thromboplastin time was prolonged similarly in each group after thrombolytic therapy. On the other hand, bleeding time was prolonged in only the heparin group after the treatment. Serious hemorrhagic side effects were not observed in all three groups. CONCLUSIONS: APC prevents coronary artery reocclusion after recanalization with rTPA in a canine model of coronary artery thrombosis. This finding suggests that APC may be useful as an adjunctive treatment to enhance the effects of thrombolytic therapy in patients with acute myocardial infarction.

Animals↗

Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced airway effects.

We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide (neurokinin) NK1 and NK2 receptor antagonists, respectively, against bronchoconstriction and airway microvascular leakage induced by inhaled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea. Each antagonist inhibited significantly the maximal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimulation alone.

Administration, Inhalation↗

Expression of platelet-activating factor receptor mRNA in human and guinea pig lung.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of several inflammatory pulmonary diseases, and specific binding sites have been demonstrated in human and guinea pig lung membranes by radioligand binding experiments. Both human and guinea pig PAF receptors (PAFR) have recently been cloned. We have used molecular probes to study the gene expression of PAFR in human and animal lung and in situ hybridization to determine the distribution of PAFR mRNA in peripheral lung. Northern blot analysis of total lung RNA from human lung parenchyma, using a 1.1-kb SmaI-EcoRI fragment of human PAFR cDNA or a 0.9-kb SmaI-SmaI fragment of guinea pig PAFR cDNA, demonstrated the expression of PAFR mRNA in human lung, with a single transcript of 4 kb. There was a significant increase in PAFR mRNA in the lungs of asthmatic patients and a significant decrease in PAFR mRNA in the lungs of cigarette smokers compared with normal patients. Similarly, the expression of PAFR mRNA on guinea pig and rat lung was detected as a single transcript of 3 kb, using both guinea pig and human PAFR cDNA probes. A full-length 1.8-kb human leukocyte PAFR cDNA probe was used as the DNA template for producing 35S-labeled antisense and sense cRNA probes for use in in situ hybridization studies of human peripheral lung. These studies revealed high levels of PAFR mRNA hybridization in blood vessels, moderate levels of hybridization in alveolar walls and peripheral airway smooth muscle, but no specific signal in airway epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗