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Biomedical subjects

Y Kishi

Publications and source records attributed to Y Kishi.

At least 127 records · Page 7Linked to original sources
PubMed1999

Effect of dipyridamole on QT dispersion in vasospastic angina pectoris.

Life-threatening ventricular arrhythmias have frequently been documented in patients with vasospastic angina. Moreover, the incidence of ventricular arrhythmias has been closely associated with increased QT dispersion. However, the underlying mechanism responsible for this arrhythmogenesis has not been clarified. The effects of dipyridamole and subsequent aminophylline administration on QT dispersion were examined in 35 patients with vasospastic angina and 30 patients with atypical chest pain. None of the patients enrolled in this study revealed any significant stenosis in coronary angiography. QT dispersion during dipyridamole followed by aminophylline administration was compared between the 2 groups. The baseline QT dispersion was similar in both groups (vasospastic angina: 27 +/- 8 ms; atypical chest pain: 28 +/- 7 ms). No significant changes in QT dispersion were observed in patients with atypical chest pain by dipyridamole (23 +/- 9 ms) and subsequent aminophylline administration (23 +/- 5 ms). However, the QT dispersion in patients with vasospastic angina increased significantly by dipyridamole administration (53 +/- 14 ms, p <0.0001) and returned to baseline by subsequent aminophylline administration (26 +/- 10 ms). Our data suggest that the disparity of ventricular repolarization in vasospastic angina may be mediated by increased endogenous adenosine.

Adult↗
PubMed1999

Oral clonidine reduces the requirement of prostaglandin E1 for induced hypotension.

PURPOSE: To determine the effects of preanesthetic oral clonidine on the dose of prostaglandin EI (PGEI) required to produce hypotension during anesthesia. METHOD: Oral placebo, 75 microg or 150 microg clonidine were administered 60 min prior to induction of anesthesia. Anesthesia was maintained with O2:N2O (30:70) and isoflurane 1.0%. After hemodynamic stabilization, an infusion of prostaglandin EI was started (0.05 microg x kg(-1) x min(-1)) and the rate of infusion was adjusted to maintain mean arterial pressure (MAP) between 60-70 mm Hg during operation. RESULTS: Duration of hypotension in placebo, 75 microg and 150 microg preanesthetic oral clonidine treated groups were 132+/-46, 117+/-37 and 129+/-56 min, respectively. The PGEI requirement in each group were 1563+/-180 (28.6+/-3.2), 594+/-197 (10.8+/-3.6) and 283+/-30 (5.5+/-3.6) microg (microg x kg(-1)), respectively. In addition, blood loss in each group were 1461+/-389, 805+/-240 and 931+/-40 ml, respectively. CONCLUSION: Preanesthetic oral clonidine decreased the dose of PGEI required to produce hypotension, and decreased the blood loss during operation.

Administration, Oral↗
PubMed1999

E5531, a synthetic non-toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide.

1. The major pathological responses to Gram-negative bacterial sepsis are triggered by endotoxin or lipopolysaccharide. As endotoxin is shed from the bacterial outer membrane, it induces immunological responses that lead to release of a variety of cytokines and other cellular mediators. As part of a program aimed at developing a therapeutic agent for septic shock, we have developed E5531, a novel synthetic lipopolysaccharide antagonist. 2. As measured by release by tumour necrosis factor-alpha, human monocytes or whole blood can be activated by lipopolysaccharide, lipid A, and lipoteichoic acid (from Gram-positive bacteria). E5531 potently antagonizes activation by all these agents while itself being devoid of agonistic activity. 3. The inhibitory activity of E5531 was dependent on time of addition. When 10 nM E5531 was added simultaneously with lipopolysaccharide or 1 - 3 h before addition of lipopolysaccharide, production of tumour necrosis factor-alpha was inhibited by more than 98%. The addition of E5531 1 h after lipopolysaccharide reduced the efficacy of E5531 by 47%. 4. Antagonistic activity of E5531 was specific for lipopolysaccharide as it was ineffective at inhibiting interferon-gamma mediated NO release of RAW 264.7 cells, phorbor 12-myristate 13-acetate stimulated superoxide anion production in human neutrophils, concanavalin A stimulated mitogenic activity in murine thymocytes and tumor necrosis factor-alpha induced E-selectin expression in human umbilical vein endothelial cells. 5. E5531 as well as MY4, an anti-CD14 antibody, inhibited radiolabelled lipopolysaccharide binding in human monocytes. 6. These results support our contention that E5531 is a potent antagonist of lipopolysaccharide-induced release of tumour necrosis factor-alpha and other cellular mediators and may be an effective therapeutic agent for human septic shock due to Gram-negative bacteria.

E-Selectin↗
PubMed1999

Flavonoids from Cleome droserifolia suppress NO production in activated macrophages in vitro.

The effect of an Egyptian medicinal plant, Cleome droserifolia (Forssk.) Del. on nitric oxide (NO) production in bacillus Calmette-Guérin-induced mouse peritoneal macrophages activated by lipopolysaccharide was investigated in vitro. The methanol extract of C. droserifolia reduced the NO production, and two flavonoids were isolated as the active components. The new one was determined to be 5,4'-dihydroxy-6,7,8,3',5'-pentamethoxyflavone (1) and the other was identified as 5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone (8-methoxycirsilineol; 2). Compound 1 concentration-dependently suppressed the NO production and was effective at a non-toxic concentration (12.5 micrograms/ml). The suppressive activity of 2 was weaker than that of 1.

Animals↗
PubMed1999

Long lasting spasticity in controlled vasospastic angina.

OBJECTIVE: To evaluate changes in coronary artery spasticity in patients with vasospastic angina who had been stable for years under continuous drug treatment. METHODS: Follow up coronary angiography was performed under intracoronary ergonovine provocation in 27 well controlled patients with vasospastic angina and no organic stenosis; the tests were done > 24 months after the initial coronary angiography, in which occlusive spasm had been induced by the same regimen of ergonovine provocation. RESULTS: The mean (SD) follow up period was 47.2 (21.6) months. All patients had been free from angina attack for more than 24 months under treatment with antianginal drugs. During this follow up period, organic stenosis developed in only one case. Occlusive spasm was observed during follow up coronary angiography in 23 patients. Spasm with 90% narrowing was observed in three other patients, and diffuse significant narrowing was seen in the final patient. No significant difference was found in spasticity (p = 0.75) between the initial and the follow up tests. CONCLUSIONS: Repeated ergonovine provocation during coronary angiography after a controlled period of several years showed that coronary spasm remains inducible in most patients. Discontinuance of drug treatment during the remission from anginal attacks achieved by medication may put the patient at high risk.

Adult↗
PubMed1999

New method of estimating myocardial infarct size using technetium-99m pyrophosphate and thallium-201 dual single photon emission computed tomography imaging.

A new method was devised to estimate infarct size using dual single photon emission computed tomography with thallium-201 and technetium-99m pyrophosphate. Designating the ratio of infarct area to whole myocardial volume as %MI, the correlation of %MI with other markers of left ventricular dysfunction was examined: peak creatine kinase, ejection fraction and left ventricular asynergy. As %MI correlated well with these markers, it is considered that %MI will be useful for estimating infarct size and predicting the severity of left ventricular dysfunction in the early stage of acute myocardial infarction.

Adult↗
PubMed1999

Microvascular changes after placement of titanium implants: scanning electron microscopy observations of machined and titanium plasma-sprayed implants in dogs.

BACKGROUND: The purpose of this study was to clarify the osseointegration process of titanium implants through study of the vascular architecture and bone apposition. The smooth machined-surface implant is tightly fixed to the bone by its threads. The rough titanium plasma-sprayed (TPS) coated implants give a scaffold for new bone. METHODS: Twelve beagle dogs were used, and 2 surface types of implants were inserted in the mandible. Vascular injection was given 14, 30, and 120 days after surgery. The soft tissue was digested by proteinase solution, and specimens were examined by scanning electron microscope (SEM). RESULTS: Fourteen days after placement of machined implants, new vessels could be seen branching out from the vascular network of the bone marrow. In TPS implants, a vascular network was seen between the bone-implant interface. At 30 days, the vessels were arranged in a groove corresponding to the machined fixture. With TPS implants, new bone was visible along the surface of the fixture, and the vascular network was buried in the bone. At 120 days after placement of machined implants, bone had formed a smooth surface. A few blood vessels were arranged along the bone surface. With TPS implants, a rough bone surface and flat vessels were observed on its surface. CONCLUSIONS: Implants become osseointegrated in different ways, depending on their structures and the characteristics of their surfaces. From the microcirculation point of view, the vessels are an important factor for the remodeling of bone.

Alveolar Process↗
PubMed1999

Alpha-lipoic acid: effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy.

The peripheral nerve of experimental diabetic neuropathy (EDN) is reported to be ischemic and hypoxic, with an increased dependence on anaerobic metabolism, requiring increased energy substrate stores. When glucose stores become reduced, fiber degeneration has been reported. We evaluated glucose uptake, nerve energy metabolism, the polyol pathway, and protein kinase C (PKC) activity in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid (0, 10, 25, 50, 100 mg/kg). Duration of diabetes was 1 month, and alpha-lipoic acid was administered intraperitoneally 5 times per week for the final week of the experiment. Nerve glucose uptake was reduced to 60, s 37, and 30% of control values in the sciatic nerve, L5 dorsal root ganglion, and superior cervical ganglion (SCG), respectively, in rats with EDN. Alpha-lipoic acid supplementation had no effect on glucose uptake in normal nerves at any dose, but reversed the deficit in EDN, with a threshold between 10 and 25 mg/kg. Endoneurial glucose, fructose, sorbitol, and myo-inositol were measured in sciatic nerve. Alpha-lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In EDN, endoneurial glucose, fructose, and sorbitol were significantly increased, while myo-inositol was significantly reduced. Alpha-lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose-dependently increased myo-inositol. Sciatic nerve cytosolic PKC was increased in EDN. ATP, creatine phosphate, and lactate were measured in sciatic nerve and SCG. Alpha-lipoic acid prevented the reduction in SCG creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose-dependently reversed by alpha-lipoic acid, a change associated with an improvement in peripheral nerve function.

Animals↗
PubMed1998

Subclavian steal syndrome secondary to Takayasu arteritis.

We present a case of 'subclavian steal syndrome' secondary to Takayasu arteritis, in a 32-year-old, Japanese woman, whose clinical manifestations result from severe ocular and brain ischemia, refractory to high dose systemic corticosteroids. Surgical management using two bypass-grafts was carried out. The first one, a GoreTex, 8 mm in diameter, thin wall, stretch type with ring-bypass graft, from the left external iliac artery to the ipsilateral axillary artery. The second one, an autologous reverse saphenous vein graft from the left subclavian artery to the ipsilateral common carotid artery. The result was a remarkable improvement of the patient's general condition and symptoms. Patency of the extra-anatomic conduits was established by digital subtraction angiography (DSA), and transcranial Doppler evaluation, as well as flow velocity assessment revealed an objective improvement of the blood supply to the ischemic areas. The present surgical approach was justified since the inflammatory process extended to the aortic arch. The development of new and efficient operatory techniques, and continuous improvement of the graft-materials provide better expectations for the long-term outcome of refractory syndromes.

Adult↗
PubMed1998

The effects of preanesthetic oral clonidine on total requirement of propofol for general anesthesia.

STUDY OBJECTIVE: To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. DESIGN: Randomized double-blinded study. SETTING: Operating room ASA physical status I and II room and recovery room of the cancer center. PATIENTS: 80 breast cancer patients scheduled for surgery. INTERVENTIONS: Patients were randomized to one of four treatment groups (placebo, clonidine 75 micrograms, or 150 micrograms of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O2): nitrous oxide (N2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. MEASUREMENTS AND MAIN RESULTS: Preanesthetic oral clonidine (150 micrograms) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 micrograms, clonidine 150 micrograms, and 10 mg of diazepam groups were 841 +/- 70 (9.0 +/- 0.3), 720 +/- 63 (7.1 +/- 0.4), 491 +/- 39 (5.6 +/- 0.2), and 829 +/- 77 mg (7.9 +/- 0.4 mg/kg/h), respectively. The cost of propofol in these groups was $51.0 +/- 3.8, $45.5 +/- 3.2, $33.5 +/- 2.3, and $50.5 +/- 4.4, respectively. CONCLUSIONS: Preanesthetic oral clonidine (150 micrograms) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 micrograms of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.

Administration, Oral↗
PubMed1998

Total synthesis and stereochemistry of cytoblastin.

The first total synthesis and stereochemical assignment of cytoblastin were reported. Key steps included the palladium-mediated coupling of N-SEM-7-bromoindolactam V ((-)-11) with allylstannane c-13, and osmium tetroxide-mediated dihydroxylation of 14, both of which were stereoselective. The stereochemistry of cytoblastin was determined as 1A via spectroscopic analysis of the pentacyclic derivative 21 of cytoblastin. A connection was then made between the stereochemistry so elucidated and the Kishi/Rando hypothesis for the structural correlation between (S)-1,2-diacylglycerol and tumor promoters for the process of protein kinase C activation.

Carcinogens↗
PubMed1998

Differentiation of Chlamydia species by combined use of polymerase chain reaction and restriction endonuclease analysis.

To differentiate Chlamydia spp., a primer pair designed to generate a genus-specific region of the major outer membrane protein (MOMP) gene was used in a PCR to amplify a single DNA fragment of 245-259 bp. In the PCR, the expected single DNA fragment was amplified from strains of Chlamydia trachomatis, C. psittaci, C. pneumoniae and C. pecorum, respectively. By restriction endonuclease analysis with AluI and PvuII, the amplified products exhibited four distinct patterns, corresponding to the four species. It is, therefore, concluded that one-step PCR followed by restriction endonuclease analysis as described in this study could be a valuable method for the detection and differentiation of Chlamydia species.

Chlamydia↗
PubMed1998

Suppression of murine endotoxin response by E5531, a novel synthetic lipid A antagonist.

As a consequence of blood-borne bacterial sepsis, endotoxin or lipopolysaccharide (LPS) from the cell walls of gram-negative bacteria can trigger an acute inflammatory response, leading to a series of pathological events and often resulting in death. To block this inflammatory response to endotoxin, a novel lipid A analogue, E5531, was designed and synthesized as an LPS antagonist, and its biological properties were examined in vitro and in vivo. In murine peritoneal macrophages, E5531 inhibited the release of tumor necrosis factor alpha (TNF-alpha) by Escherichia coli LPS with a 50% inhibitory concentration (IC50) of 2.2 nM, while E5531 elicited no significant increases in TNF-alpha on its own. In support of a mechanism consistent with antagonism of binding to a cell surface receptor for LPS, E5531 inhibited equilibrium binding of radioiodinated LPS ([125I]2-(r-azidosalicylamido)-1, 3'-dithiopropionate-LPS) to mouse macrophages with an IC50 of 0.50 microM. E5531 inhibited LPS-induced increases in TNF-alpha in vivo when it was coinjected with LPS into C57BL/6 mice primed with Mycobacterium bovis bacillus Calmette-Guérin (BCG). In this model, the efficacy of E5531 was inversely correlated to the LPS challenge dose, consistent with a competitive antagonist-like mechanism of action. Blockade of the inflammatory response by E5531 could further be demonstrated in other in vivo models: E5531 protected BCG-primed mice from LPS-induced lethality in a dose-dependent manner and suppressed LPS-induced hepatic injury in Propionibacterium acnes-primed or galactosamine-sensitized mice. These results argue that the novel synthetic lipid A analogue E5531 can antagonize the action of LPS in in vitro and suppress the pathological effects of LPS in vivo in mice.

Animals↗
PubMed1998

High levels of actin tyrosine phosphorylation: correlation with the dormant state of Dictyostelium spores.

Upon removal of nutrients, the amoebae of the cellular slime mold Dictyostelium discoideum differentiate into dormant spores which survive starvation stress. In this study, we demonstrate that half of the actin molecules in the spores are tyrosine-phosphorylated. The phosphorylated actin is distributed around immobile crenate mitochondria and vesicles, as well as in the cytoplasm of the spores. The actin isolated from spore lysates contains phosphorylated and unphosphorylated forms at the same molar ratio as that of the original whole spore lysate. Under actin polymerizing conditions they form actin filaments and then they are completely depolymerized under actin depolymerizing conditions, indicating that tyrosine phosphorylation of actin may not prohibit actin polymerization nor stimulate depolymerization. The phosphorylation levels increase at the end of the culmination stage when spores have matured morphologically and physiologically, and reach maximum levels after an additional 12 hours of development. The levels are stable for 20 days following spore maturation, and decline to undetectable levels within the next 10 days. Spores having high levels of phosphorylation show high viability, and vice versa. Following activation of spores with nutrient medium containing spore germination promoters, the phosphorylation levels quickly decrease with a half-life of about 5 minutes. After 20 minutes spores begin to swell. At this later time, most of the phosphorylated actin already has been dephosphorylated. Also, in heat-activated spores actin dephosphorylation occurs prior to spore swelling. However, addition of phosphatase inhibitors following heat-activation, prevented spore swelling and dephosphorylation of actin. Our data indicate that the high levels of actin tyrosine phosphorylation, specific to the spore stage, may be required for maintaining dormancy to withstand starvation stress. The rapid dephosphorylation of actin leads to a reactivated dynamic actin system which participates in spore swelling, vesicle movement, and mitochondrial shape changes during the spore germination process.

Actins↗
PubMed1998

Long-term patency of an aorta-aortic graft bypass in a patient with Takayasu arteritis.

A 39-year-old woman was diagnosed by means of angiography as Takayasu arteritis complicated with severe systemic hypertension due to atypical coarctation of the aorta. Aorta-aortic bypass graft surgery was carried out successfully and hypertension remarkably improved. An evaluation of the graft 23 years later confirmed an almost perfect condition with a very satisfactory clinical status. Extensive long-term follow-up studies have been conducted among young people after surgical repair of aortic coarctation showing encouraging results, however the situation seems to be different for the atypical coarctation in Takayasu patients, since not only the age at the time of intervention affects the outcome, but the different circumstances mainly related to the natural history of the disease. We evaluated the long-term outcome based on similar cases with particular consideration to the extremely rare coexistence of familiar hypercholesterolemia.

Adult↗