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Biomedical subjects

Takeshi Yokoyama

Publications and source records attributed to Takeshi Yokoyama.

At least 19 recordsLinked to original sources
PubMed2007

Age and sex-related differences in dose-dependent hemodynamic response to landiolol hydrochloride during general anesthesia.

OBJECTIVE: Landiolol hydrochloride is a new ultra-short-acting beta(1)-adrenergic receptor blocking agent that is used for patients with tachycardia during general anesthesia. The hemodynamic response to a beta-adrenergic receptor blocking agent is generally dependent on the subject. In the present investigation we investigated the effects of age and sex on the hemodynamic response to different doses of landiolol. METHODS: Following a persistence of tachycardia for more than 1 min, landiolol was infused at 0.03125, 0.0625 and 0.125 mg kg(-1) min(-1) for 1 min followed by 0.01, 0.02 and 0.04 mg kg(-1)min(-1) for 10 min in groups L, M and H, respectively. Heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) were recorded each minute during the procedure. The respective changes were evaluated using logistic analysis with the equation Y(t) = p + (q - p)/[1 + exp {4m/(q - p))(k - t)}], where p, q, m and k indicate the upper asymptote, lower asymptote, maximum slope and time at the maximum slope. RESULTS: Parameters q and k for HR in group H were smaller than those in group L, whereas the parameters for sBP and dBP were unchanged among the three groups. Parameter q for HR in group H decreased with age of the patient. There was no significant difference in the landiolol-induced change in HR between males and females. CONCLUSION: The hemodynamic response to landiolol is reliably modeled by the logistic function, especially in terms of HR. Landiolol causes a rapid and dose-dependent decrease in HR, whereas landiolol-induced changes in sBP and dBP are independent of dose. The landiolol-induced decrease in HR becomes larger with aging, but shows no sex difference. The logistic model may be useful for studying hemodynamic responses to landiolol based on age and sex differences, and may allow development of an improved monitoring system. IMPLICATION STATEMENT: The logistic function reliably represents the hemodynamic responses to landiolol. Landiolol reduces HR rapidly and in a dose-dependent manner whereas landiolol-induced changes in sBP and dBP are independent of dose. A larger decrease in HR is caused by landiolol in elderly patients, but there is no sex difference in the landiolol-induced change in HR.

Adrenergic beta-Antagonists↗
PubMed2006

Crystal structure of oxidized cytochrome c(6A) from Arabidopsis thaliana.

Compared with algal and cyanobacterial cytochrome c(6), cytochrome c(6A) from higher plants contains an additional loop of 12 amino acid residues. We have determined the first crystal structure of cytochrome c(6A) from Arabidopsis thaliana at 1.5 Angstrom resolution in order to help elucidate its function. The overall structure of cytochrome c(6A) follows the topology of class I c-type cytochromes in which the heme prosthetic group covalently binds to Cys16 and Cys19, and the iron has octahedral coordination with His20 and Met60 as the axial ligands. Two cysteine residues (Cys67 and Cys73) within the characteristic 12 amino acids loop form a disulfide bond, contributing to the structural stability of cytochrome c(6A). Our model provides a chemical basis for the known low redox potential of cytochrome c(6A) which makes it an unsuitable electron carrier between cytochrome b(6)f and PSI.

Arabidopsis↗
PubMed2006

1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms.

The most recent refinement of the crystallographic structure of oxyhaemoglobin (oxyHb) was completed in 1983, and differences between this real-space refined model and later R state models have been interpreted as evidence of crystallisation artefacts, or numerous sub-states. We have refined models of deoxy, oxy and carbonmonoxy Hb to 1.25 A resolution each, and compare them with other Hb structures. It is shown that the older structures reflect the software used in refinement, and many differences with newer structures are unlikely to be physiologically relevant. The improved accuracy of our models clarifies the disagreement between NMR and X-ray studies of oxyHb, the NMR experiments suggesting a hydrogen bond to exist between the distal histidine and oxygen ligand of both the alpha and beta-subunits. The high-resolution crystal structure also reveals a hydrogen bond in both subunit types, but with subtly different geometry which may explain the very different behaviour when this residue is mutated to glycine in alpha or beta globin. We also propose a new set of relatively fixed residues to act as a frame of reference; this set contains a similar number of atoms to the well-known "BGH" frame yet shows a much smaller rmsd value between R and T state models of HbA.

Amino Acid Sequence↗
PubMed2006

Artificial baroreflex: clinical application of a bionic baroreflex system.

BACKGROUND: We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial baroreflex system to automatically regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we tested its efficacy in a model of sudden hypotension during surgery. METHODS AND RESULTS: The BBS consisted of a computer-controlled negative-feedback circuit that sensed arterial pressure (AP) and automatically computed the frequency (STM) of a pulse train required to stimulate sympathetic nerves via an epidural catheter placed at the level of the lower thoracic spinal cord. An operation rule was subsequently designed for the BBS using a feedback correction with proportional and integral gain factors. The transfer function from STM to AP was identified by a white noise system identification method in 12 sevoflurane-anesthetized patients undergoing orthopedic surgery involving the cervical vertebrae, and the feedback correction factors were determined with a numerical simulation to enable the BBS to quickly and stably attenuate an external disturbance on AP. The performance of the designed BBS was then examined in a model of orthostatic hypotension during knee joint surgery (n=21). Without the implementation of the BBS, a sudden deflation of a thigh tourniquet resulted in a 17+/-3 mm Hg decrease in AP within 10 seconds and a 25+/-2 mm Hg decrease in AP within 50 seconds. By contrast, during real-time execution of the BBS, the decrease in AP was 9+/-2 mm Hg at 10 seconds and 1+/-2 mm Hg at 50 seconds after the deflation. CONCLUSIONS: These results suggest the feasibility of a BBS approach for central baroreflex failure.

Aged↗
PubMed2006

Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in abdominal surgery.

PURPOSE: Ulinastatin is well known to inhibit the activity of polymorphonuclear leukocyte elastase (PMNE). The PMNE concentration correlates with the activities of coagulation and fibrinolysis. The purpose of the present study was to investigate the effects of ulinastatin, a protease inhibitor, on coagulation and fibrinolysis in abdominal surgery. METHODS: Thirty patients, aged 40 to 70 years, with American Society of Anesthesiologists (ASA) physical status I or II, scheduled for major abdominal surgery, were enrolled. Anesthesia was induced with midazolam and thiopental, and was maintained with sevoflurane, nitrous oxide in oxygen, and an epidural block. An infusion of ulinastatin, 6000 units x kg(-1) in 30 min, was started 1 h after the start of surgery in the ulinastatin group (15 patients). In the control group (15 patients), no protease inhibitors were infused. White blood cell count; platelet count; prothrombin time; activated partial thromboplastin time; and plasma concentrations of PMNE, antithrombin (AT), fibrin/fibrinogen degradation product (FDP), fibrinogen, plasminogen, plasmin-(alpha2) plasmin inhibitor complex (PIC), and thrombin-antithrombin complex (TAT) were measured before, at the end of, and 12 h after surgery. RESULTS: TAT, PIC, and FDP after surgery were significantly lower in the ulinastatin group than in the control group. AT was decreased in the control group but not in the ulinastatin group, with significant differences between the two groups. CONCLUSION: Ulinastatin could inhibit coagulation and fibrinolysis in abdominal surgery.

Abdomen↗
PubMed2006

Rounding up: Engineering 12-membered rings from the cyclic 11-mer TRAP.

The protein TRAP (trp RNA binding attenuation protein) forms a highly thermostable ring-shaped 11-mer. By linking in tandem two, three, or four DNA sequences encoding TRAP monomers, we have engineered new rings that consist of 12 TRAP subunits and bind 12 ligand molecules. The hydrogen bonding pattern and buried surface area within and between subunits are essentially identical between the 11-mer and 12-mer crystal structures. Why do the artificial proteins choose to make single 12-mer rings? The 12-mer rings are highly sterically strained by their peptide linkers and far from thermostable. That proteins choose to adopt a strained conformation of few subunits rather than an unstrained one with 11 subunits demonstrates the importance of entropic factors in controlling protein-protein interactions in general.

Bacterial Proteins↗
PubMed2006

Implementation of a 20-nm pore-size filter in the plasma-derived factor VIII manufacturing process.

BACKGROUND AND OBJECTIVES: Virus inactivation and removal are important prerequisites to ensure the safety of plasma derivatives. For virus inactivation and removal in our coagulation factor VIII (FVIII) product, CROSS EIGHT M, the production process consists of solvent-detergent (S/D) treatment, two chromatography steps and virus filtration with a 35-nm pore-size filter. However, the clearance of non-enveloped viruses was not as good as that of enveloped viruses because non-enveloped viruses are resistant to S/D treatment and are too small to be removed by the filter. In this study, in order to improve the viral safety of the FVIII products, we attempted to replace the 35-nm pore-size virus filter with a 20-nm filter. MATERIALS AND METHODS: The virus-filtration process was validated for the removal of enveloped and non-enveloped model viruses. Several factors that might affect the FVIII yield on filtration were investigated to obtain a higher recovery. The biochemical properties of the FVIII products produced with the 20-nm pore-size filter were compared with those produced by the 35-nm filter. RESULTS: Virus filters of 20-nm pore size effectively removed the small non-enveloped viruses when compared with the 35-nm pore-size virus filter. The permeability of FVIII through the 20-nm pore-size filter was inversely proportional to the concentration of FVIII at filtration, and directly proportional to the amount of postfiltration solution. No differences were observed in the biochemical properties of both FVIII products, such as the structure and stability of the FVIII, the contents and multimeric structure of von Willebrand factor (vWF), and FVIII activation by thrombin. CONCLUSIONS: The virus-clearance efficiency of the FVIII product, CROSS EIGHT M, was markedly increased, in particular against small non-enveloped viruses, by changing the virus filter pore size from 35 nm to 20 nm. It was possible to implement the 20-nm pore-size filter without variation of the biochemical properties or a serious loss of FVIII.

Factor VIII↗
PubMed2006

[A case of sudden occurrence of complete left bundle branch block during emergency surgery].

We experienced a case of sudden occurrence of complete left bundle branch block during emergency surgery. A 59-year-old man suffered from facial bone fracture and eye ball injury. Repair of facial bone and removal of eye ball surgery were scheduled. Chest X-ray, echocardiography, blood counts and laboratory data were within normal limits. Awake intubation was performed. Anesthesia was maintained with 2-3% sevoflurane in 1 l x min(-1) of oxygen and 2 l x min(-1) of nitrous oxide. After induction of anesthesia, tracheostomy was performed with combined use of local anesthesia with 6 ml of 1% lidocaine with 1/200000 epinephrine. Then removal of eye ball surgery was started and finished uneventfully. During repair of facial bone fracture, we found an unexpected complete left bundle branch block. After rapid infusion of 1000 ml acetic Ringer's solution, the complete left bundle branch block disappeared. After surgery, mannitol administration at the previous hospital was noticed. Complete left bundle branch block in this case might have been induced by hypovolemia and hyperpotassemia due to osmotic diuresis by mannitol.

Bundle-Branch Block↗
PubMed2005

R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35.

Although detailed crystal structures of haemoglobin (Hb) provide a clear understanding of the basic allosteric mechanism of the protein, and how this in turn controls oxygen affinity, recent experiments with artificial effector molecules have shown a far greater control of oxygen binding than with natural heterotropic effectors. Contrary to the established text-book view, these non-physiological compounds are able to reduce oxygen affinity very strongly without switching the protein to the T (tense) state. In an earlier paper we showed that bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb, strongly reducing the oxygen affinity of this protein conformation. Here we report the crystallisation of Hb with L35, a related compound, and show that this binds to the central cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen affinity is discussed, in relation to spectroscopic studies of effector binding.

Animals↗
PubMed2005

Cardiac output by PulseCO is not interchangeable with thermodilution in patients undergoing OPCAB.

PURPOSE: To investigate the reliability of cardiac output assessed by arterial pressure waveform (PulseCO) in comparison with bolus thermodilution measurements in patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS: 23 patients who underwent OPCAB were enrolled in this study. After premedication with oral diazepam 10 mg, anesthesia was induced with midazolam, fentanyl and vecuronium. After induction, radial artery and pulmonary artery catheters were inserted. Cardiac output was measured simultaneously by the PulseCO and the bolus thermodilution method using the Vigilance monitor: 1) after sternotomy, 2) after opening the mediastinum, and 3) at the end of surgery. The PulseCO was calibrated initially with cardiac output determined by the thermodilution method after induction of anesthesia. RESULTS: The correlation coefficients between the two techniques at the three measurement periods were: 1) R2 = 0.49, 2) R2 = 0.52, 3) R2 = 0.55. The limits of agreement (bias +/- 2 SD of bias) were: 1) 0.71 +/- 2.66, 2) 0.30 +/- 1.97, 3) 0.76 +/- 3.85 L.min(-1). CONCLUSIONS: Cardiac output by PulseCO is not interchangeable with cardiac output measured by thermodilution in patients undergoing OPCAB.

Aged↗
PubMed2005

Blood flow velocity of the femoral vein with foot exercise compared to pneumatic foot compression.

STUDY OBJECTIVE: To compare the effects of foot exercise with an intermittent pneumatic foot compression (IPC) device on blood flow velocity of the femoral veins. DESIGN: Prospective, controlled study. SETTING: General intensive care unit of a university hospital. PATIENTS: 20 patients on bed rest in the intensive care unit. INTERVENTIONS: Patients were divided into 2 groups: group A, foot exercise (n = 10); and group B, IPC device (n = 10). The foot exercise was done once by a nurse for 5 minutes with the dorsiflexion of the ankle (15 times per minute) in group A patients. The IPC device (A-V Impulse System, compression setting: 130 mm Hg for 3 seconds followed by a resting period of 60 seconds) was used for 2 hours in group B. MEASUREMENTS: Peak blood flow velocity of the femoral vein was measured using the ultrasound unit with a 7.5-MHz linear array probe (ALOKA SSD-5500) at 0, 5, 15, 30, 60, and 120 minutes. MAIN RESULTS: Peak blood flow velocities in both groups increased significantly vs the control values during the study. At 5 minutes, group A showed a significant increase in the peak blood flow velocity compared with group B. CONCLUSIONS: Foot exercise by a nurse for 5 minutes was equally or more effective compared with the IPC device in increasing peak blood flow velocity of the femoral vein. The effect of the 5-minute foot exercise lasted for 2 hours.

Aged↗
PubMed2005

Stress hormone changes in general anesthesia of long duration: isoflurane-nitrous oxide vs sevoflurane-nitrous oxide anesthesia.

STUDY OBJECTIVE: There are few comparative studies of stress hormone changes during general anesthesia with long duration between isoflurane-nitrous oxide and sevoflurane-nitrous oxide anesthesia. We investigated perioperative changes of stress hormone in these two anesthetic methods with duration of more than 10 hours. DESIGN: Prospective study. SETTING: Operating room and high care unit of a university hospital. PATIENTS: Twenty patients with ASA physical status I or II for surgery for laryngeal or pharyngeal cancer with expected duration of more than 10 hours. INTERVENTIONS: Anesthesia was induced with midazolam, thiopental, and vecuronium and was maintained with sevoflurane (sevoflurane group) or isoflurane (isoflurane group) with nitrous oxide 4 L/min in oxygen 2 L/min. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of epinephrine, norepinephrine, cortisol, adrenocorticotropic hormone, and anti-diuretic hormone (ADH); serum concentrations of glucagon and insulin; and blood glucose concentration were measured before inhalation of anesthetics, after 5 and 10 hours, and at 1, 6, and 12 hours after the end of inhalation. Epinephrine and norepinephrine concentrations increased continuously during and after surgery in the isoflurane group whereas it increased only after surgery in the sevoflurane group. Both concentrations were higher in the isoflurane group during anesthesia. Cortisol increased continuously whereas adrenocorticotropic hormone increased only during surgery. Anti-diuretic hormone increased with its peak during surgery and the isoflurane group had significantly higher values than the sevoflurane group. Glucose increased both during and after surgery, insulin increased only after surgery, and glucagon decreased during surgery in both groups. CONCLUSIONS: In inhalation anesthesia with the duration of more than 10 hours, isoflurane-nitrous oxide and sevoflurane-nitrous oxide had the same effects on stress hormone changes except for epinephrine, norepinephrine, and ADH. Epinephrine, norepinephrine, and ADH concentrations were higher in isoflurane-nitrous oxide anesthesia.

Adrenocorticotropic Hormone↗
PubMed2005

A comparison of the rate of bacterial contamination for prefilled disposable and reusable oxygen humidifiers.

BACKGROUND: Prefilled disposable oxygen humidifiers are considered to prevent nosocomial pneumonia in hospital wards. However, their usefulness in intensive care units (ICUs) has not yet been established. In this study, we evaluated and compared contamination in prefilled disposable oxygen humidifiers and that in reusable oxygen humidifiers. METHODS: Six oxygen outlets in the ICU were used. Prefilled disposable oxygen humidifiers and reusable oxygen humidifiers were attached to each wall-mounted oxygen outlet using a 2-way connector. Nonsterile nasal cannulae and tubes were connected to the humidifiers through which 5 L/min of oxygen was delivered continuously. Water samples (5 mL) from each humidifier were collected on the first day and every 7 days thereafter for a period of 56 days. Each water sample was incubated aerobically at 35 degrees C for 48 hours and observed daily for bacterial growth. RESULTS: Bacterial growth was observed only once in one sample from each humidifier type. Gram-positive cocci, 40 colony-forming units in the disposable oxygen humidifier and 10 colony-forming units in the reusable oxygen humidifier, were detected. Dust was observed from the 35th day onward only in the reusable oxygen humidifier. CONCLUSION: In the ICU, bacterial contamination does not occur in oxygen humidifiers even after 56 days of continuous use. However, dust does accumulate in the reusable oxygen humidifier after 35 days of continuous use.

Equipment Contamination↗
PubMed2005

Selective cyclooxygenase 2 inhibitor induces indefinite survival of fully allogeneic cardiac grafts and generates CD4+ regulatory cells.

BACKGROUND: Selective inhibition of cyclooxygenase 2 has been reported to have not only anti-inflammatory effects but also effects on the immune response. We investigated ability of a cyclooxygenase 2 inhibitor to inhibit alloimmune response in a murine cardiac transplantation model. METHODS: CBA (H2(k)) mice underwent transplantation of C57BL/10 (H2(b)) hearts. On the day of transplantation, the recipients received either no treatment or single administration of aspirin (a cyclooxygenase 1 and 2 inhibitor) or the selective cyclooxygenase 2 inhibitor NS-398. Naive CBA mice (secondary recipients) underwent adoptive transfer of splenocytes from treated mice with long-surviving grafts (primary recipients) to determine whether regulatory cells developed after NS-398 treatment. Histologic, cell-proliferation, and cytokine studies were also performed. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time, 8 days). The majority of recipients given aspirin rejected their grafts within 20 days (median survival time, 11 days). In mice given NS-398, the majority of the grafts survived indefinitely (median survival time, >100 days). Secondary CBA recipients given CD4+ splenocytes from primary CBA recipients treated with NS-398 also had indefinite survival of C57BL/10 hearts (median survival time, >60 days). Graft acceptance and proliferative hyporesponsiveness were also confirmed by the histologic and cell-proliferation studies, respectively. Production of interleukin 4 and 10 from splenocytes of the recipients treated with NS-398 were significantly higher than that from untreated recipients. CONCLUSIONS: In our model administration of cyclooxygenase 2 inhibitor induced indefinite survival of fully mismatched cardiac grafts and generated CD4+ regulatory cells. Cyclooxygenase 2 inhibitor could warrant consideration for use as an immunomodulating agent in clinical transplantation.

Animals↗
PubMed2005

[A case of thoraco-amniotic shunt for congenital cystic adenomatoid malformation].

Congenital cystic adenomatoid malformation (CCAM) is a congenital pulmonary anomaly, which may lead to fetal hydrops, pulmonary hypoplasia, and fetal or neonatal death. Recently, diagnosis and surgery for fetus have been improved. We experienced a case of CCAM, classified in Stocker class I, with a single cyst of about 5 cm in diameter. A 32 year-old pregnant woman had a fetus diagnosed as CCAM at 25 th gestational week. The thoraco-amniotic shunt placement using a modified double pig tail catheter was performed at 27 th gestational week under general anesthesia with 1% isoflurane in oxygen 2 l x min(-1) and nitrous oxide 4 l x min(-1), and 100 microg of fentanyl. Fetal movement was suppressed during surgery. This fetal therapy was effective and the cyst disappeared after surgery. The baby was delivered with caesarian section under spinal anesthesia with 0.5% bupivacaine 2.5 ml. On the next day, right lung lobectomy was accomplished under general anesthesia with fentanyl 0.2 mg and pancuronium 6.0 mg. Anesthesia with isoflurane, nitrous oxide, and fentanyl was useful for the fetal surgery of thoraco-amniotic shunt placement. Consequently, caesarian section and lung lobectomy were completed successfully.

Adult↗