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Biomedical subjects

Y Nakata

Publications and source records attributed to Y Nakata.

At least 73 records · Page 4Linked to original sources

Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions.

Jumping translocations (JTs) are unbalanced chromosomal translocations in which an identical chromosomal region is translocated to the telomeric region of different chromosomes. JTs are rare in hematological malignancies where they are second translocations and may be an indicator of poor prognosis. We report a case of acute myeloid leukemia with t(16;21) and a JT in which the long arm of chromosome 1 distal to q21 is translocated to the terminal region of chromosome 10. The leukemic cells exhibit high expression of EAT/mcl1, an anti-apoptotic Bcl-2 related gene. Since EAT/mcl1 is mapped to 1q21 near the breakpoint in the JTs, high level expression of EAT/mcl1 may be associated with the poor prognosis of leukemia with JTs.

Adolescent↗

IL-18 in pregnancy; the elevation of IL-18 in maternal peripheral blood during labour and complicated pregnancies.

Serum interleukin-18 (IL-18) levels were measured in women in different trimesters of pregnancy, in labour, puerperium and in various complicated pregnancies. There was a significant elevation of IL-18 levels in pregnant sera from the first trimester until the onset of labour. Once labour began, IL-18 levels increased further and remained until at least the third day of puerperium. The high levels of IL-18 in sera were also observed in various complicated pregnancies, such as premature rupture of membranes (PROM), acute fatty liver of pregnancy and fetal growth restriction. IL-18 is likely to play a role in pregnancy.

Female↗

Lithium chloride inhibits thrombin-induced intracellular calcium mobilization in C6 rat glioma cells.

In this study, the authors have demonstrated the effect of lithium, a typical mood stabilizer, on thrombin-evoked Ca2+ mobilization in C6 cells to elucidate the action mechanisms of the drug. Thrombin-induced Ca2 mobilization was reduced 24 hr after 1 or 10 mM lithium chloride (LiCl) pretreatment. The Ca2+ rise was reduced in a time-dependent manner, and the significant inhibition was observed 9 hr pretreatment with 10 mM LiCl. On the other hand, pretreatment of the cells with 10 mM LiCl for 24 hr did not alter the amount of Galphaq/11 significantly. Pretreatment with 10 mM LiCl for 24 hr failed to reduce the 5-HT-induced Ca2+ mobilization or to affect the desensitization of the 5-HT signal. Finally, thrombin-elicited Ca2+ rise was markedly inhibited in the presence of 0.05 U/ml plasmin, however, the Ca2+ rise was not further attenuated in the presence of plasmin in C6 cells pretreated with LiCl for 24 hr. These results indicate that pretreatment with LiCl attenuated thrombin-evoked intracellular Ca2+ mobilization in plasmin sensitive manner in C6 rat glioma cells. Thus, it is important to investigate the effect of lithium on thrombin-induced cellular responses to clarify the action mechanism of lithium in relation to some abnormality in thrombin-evoked Ca2+ rise observed in bipolar disorders.

Animals↗

Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho.

OBJECTIVE: The functions of a small GTP-binding protein, Rho, in human leukemic cell invasion was investigated in vivo and in vitro. MATERIALS AND METHODS: Human leukemic KM3 and Reh cells (derived from B-cell-type common acute lymphoid leukemias) were inoculated into severe combined immundeficiency (SCID) mice. Alteration of invasion in SCID mice inoculated with KM3 cells that were introduced with the expression vector for Rho Val14 (Rho V14), an activated mutant form of Rho, was observed. RESULTS: SCID mice inoculated with KM3 and Reh cells developed paraplegia 21 days after inoculation. All died by day 26-27. The leukemic cells were localized to bone marrow and around the spinal cord, with no infiltration into peripheral blood, spleen, liver, thymus, or lymph nodes. SCID mice inoculated with Rho V14-transfected KM3 cells showed a 5-day reduction in the time to paraplegia and death compared with SCID mice inoculated with hygromycin-resistance gene-transfected KM3 (hyg(r)) cells. In addition, the mice inoculated with Rho V14 cells showed leukemic cell infiltration, not only into bone marrow and around the spinal cord but also into peripheral blood, liver, and spleen. There were no in vitro or in vivo differences in growth rates of Rho V14 and hyg(r) cells. However, the Rho V14 cells showed markedly increased cell adhesion compared to the hyg(r) cells. CONCLUSION: Results suggest that Rho activation accelerates human leukemic cell invasion via augmentation of cell adhesion.

Animals↗

Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure.

The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimetric G proteins (GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/ C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele (P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.

Adult↗

Risk attitudes of anesthesiologists and surgeons in clinical decision making with expected years of life.

STUDY OBJECTIVE: To understand anesthesiologists' and surgeons' risk attitudes about expected years of life. DESIGN: Prospective study. SETTING: Central operating rooms (ORs) in a university hospital. RESPONDENTS: 122 anesthesiologists and surgeons. MEASUREMENTS AND MAIN RESULTS: A 7-page survey questionnaire regarding the length of survival and the choice of treatments was sent to 122 physicians. Certainty equivalents and Arrow-Pratt coefficients of absolute risk aversion (APC) were calculated from the survey. Of 122 physicians, 93 responded (38 anesthesiologists and 55 surgeons; response rate 76. 2%). There was no significant difference in risk attitudes between the anesthesiologists and the surgeons. Their age was a statistically significant predictor of the risk attitudes: the older they were, the greater their APCs were (i.e., the more risk averse they were). There was no significant difference between gender in risk attitudes, nor was there any significant difference between the risk attitudes of becoming patients and those of working in the OR. CONCLUSIONS: Physicians' risk attitudes cannot be predicted by their specialties or gender. However, the older they are, the more risk-averse they are.

Adult↗

Effect of xenon on autonomic cardiovascular control--comparison with isoflurane and nitrous oxide.

STUDY OBJECTIVES: To clarify the effect of xenon on the autonomic nervous system by comparing similar effects of isoflurane and nitrous oxide. DESIGN: Prospective, randomized study. SETTING: Operating room at a university hospital. PATIENTS: 39 ASA physical status I and II patients scheduled for general anesthesia. INTERVENTIONS: Patients were randomly allocated into one of three groups and received one of the following inhalational anesthetics: 56% of xenon (Group X), 0.94% of isoflurane (Group I), or 70% of nitrous oxide and 0.15% of isoflurane (Group N). Phenylephrine (pressor test) and nicardipine (depressor test) were given to assess baroreflex sensitivity. MEASUREMENTS AND MAIN RESULTS: Continuous blood pressure (BP) and electrocardiogram (ECG) were recorded before and during anesthesia to analyze heart rate (HR) variability and baroreflex sensitivity. Power spectrum of HR variability was calculated by fast Fourier transformation and power spectrum densities at low frequency (LF: 0.04-0.15Hz) and high frequency (HF: 0.15-0.40 Hz) were compared. Baroreflex sensitivity was calculated from the slope of regression for BP changes versus associated changes in R-R intervals. For HR variability, Group X showed lower power spectrum densities (ms(2).Hz(-1)) in LF and HF than did Group I (LF: 0.09 +/- 0.06 vs. 0.35 +/- 0.53; p < 0.05; HF: 0.40 +/- 0.34 vs. 0.98 +/- 0.68, p < 0.01). Group X had the lowest baroreflex sensitivity (ms.mmHg(-1)) via pressor test of the three study groups (Group X: 2.00 +/- 0.87, Group I: 3.53 +/- 2.14, Group N: 3.78 +/- 2. 17, p < 0.05). CONCLUSIONS: Xenon depressed both sympathetic and parasympathetic transmission more than isoflurane at 0.8 MAC. Xenon was also suggested to be relatively vagotonic.

Adolescent↗

Effect of xenon on endotracheal tube cuff.

STUDY DESIGN: To investigate the effect of xenon on the endotracheal tube cuff in comparison to that of nitrous oxide. DESIGN: Prospective, randomized study. SETTING: Laboratory in vitro testing of endotracheal tubes. INTERVENTIONS: Exposure of air-filled endotracheal tube cuffs to xenon or nitrous oxide (79 vol%) mixed with a balance of oxygen (21 vol%) for 3 hours. MEASUREMENTS: The intra-cuff pressure and gas volume in the cuff were measured for 3 hours. MAIN RESULTS AND CONCLUSION: Increase in pressure and gas volume was significantly less and slower with xenon than with nitrous oxide. More nitrous oxide passes into the cuff than xenon.

Air Pressure↗

Deletion polymorphism of angiotensin-converting enzyme gene is associated with postprandial hyperglycaemia in individuals undergoing general check-up.

1. Deletion polymorphism, DD, of the angiotensin-converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance. 2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 nondiabetic men (age range 30-60 years) undergoing general check-up. 3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively. 4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype. 5. The mean (+/- SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8 +/- 6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6 +/- 2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes. 6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes. 7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.

Adult↗

Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia.

Brain microglia are a major source of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), which have been implicated in the progression of neurodegenerative diseases. Recently, microglia were revealed to be highly responsive to ATP, which is released from nerve terminals, activated immune cells, or damaged cells. It is not clear, however, whether released ATP can regulate TNF-alpha secretion from microglia. Here we demonstrate that ATP potently stimulates TNF-alpha release, resulting from TNF-alpha mRNA expression in rat cultured brain microglia. The TNF-alpha release was maximally elicited by 1 mM ATP and also induced by a P2X(7) receptor-selective agonist, 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, suggesting the involvement of P2X(7) receptor. ATP-induced TNF-alpha release was Ca(2+)-dependent, and a sustained Ca(2+) influx correlated with the TNF-alpha release in ATP-stimulated microglia. ATP-induced TNF-alpha release was inhibited by PD 098059, an inhibitor of extracellular signal-regulated protein kinase (ERK) kinase 1 (MEK1), which activates ERK, and also by SB 203580, an inhibitor of p38 mitogen-activated protein kinase. ATP rapidly activated both ERK and p38 even in the absence of extracellular Ca(2+). These results indicate that extracellular ATP triggers TNF-alpha release in rat microglia via a P2 receptor, likely to be the P2X(7) subtype, by a mechanism that is dependent on both the sustained Ca(2+) influx and ERK/p38 cascade, regulated independently of Ca(2+) influx.

Adenosine Triphosphate↗

Bispectral analysis of the electroencephalogram does not predict responsiveness to verbal command in patients emerging from xenon anaesthesia.

The bispectral index (BIS) is derived empirically from the electroencephalogram database of patients receiving common anaesthetics, but it may not be valid for uncommon agents. Therefore, we investigated how xenon affects the BIS. Nine and 11 patients were anaesthetized with 0.8 of the minimal alveolar concentration (MAC) of isoflurane (0.92%) and xenon (56%), respectively. After the end of operation, these concentrations were decreased in decrements of 0.1 MAC (isoflurane 0.12% or xenon 7%) and each new concentration was maintained for 15 min. This was repeated until the patient first opened her eyes or squeezed the investigator's hand on command. Isoflurane and xenon at 0.8 MAC reduced the BIS to a median of 40 (range 36-53) and 36 (30-61), respectively. With decreasing concentrations of isoflurane, the BIS increased progressively and it reached a median of 96 (90-98) when the patients awoke. In contrast, four patients receiving xenon responded to verbal command while the BIS was below 50 [median 45 (range 41-49)]. The remaining seven patients in the xenon group awoke when their BIS was greater than 80 [median 96 (range 82-98)], but in four of them the BIS was no greater than 50 when the xenon concentration was only 0.1 MAC (7%) higher than that associated with awakening. We conclude that low BIS values (< 50) do not guarantee adequate hypnosis during xenon anaesthesia.

Adult↗

Control of CD4 T cell fate by antigen re-stimulation with or without CTLA-4 engagement 24 h after priming.

After two consecutive inoculations with Staphylococcus enterotoxin B (SEB) at 24 h intervals in vivo, CD4 T cells became anergic to the antigen challenge in vitro. Administration of anti-CTLA-4 mAb in conjunction with the second SEB inoculation 24 h after antigen priming interfered with anergy and CD4 T cells became T(h)2 cells. However, the anergy induction was not ablated when SEB and anti-CTLA-4 mAb were administered 48 or 72 h after antigen priming. Moreover, anti-CTLA-4 mAb without SEB did not interfere with anergy nor promoted the T(h)2 differentiation. T-antigen-presenting cell (APC) interaction in vitro in the presence of high doses of antigen and anti-CTLA-4 mAb induced a T(h)2-polarizing cytokine IL-6 and IL-10. IL-10 then down-modulated a T(h)1-polarizing cytokine IL-12. The results demonstrate that 24 h after the initial antigen stimulation, CD4 T cells enter the critical activation phase where antigen re-stimulation with or without CTLA-4 engagement alters the fate of the cell, anergy or differentiation respectively. Once anergy is interfered with, T(h)2-polarizing cytokines produced upon prolonged T-APC interaction favor the T(h)2 differentiation.

Abatacept↗

Emergence agitation after sevoflurane versus propofol in pediatric patients.

UNLABELLED: Sevoflurane may be associated with a high incidence of emergence agitation in preschool children. We tested the hypothesis that maintenance of anesthesia with propofol after sevoflurane induction would reduce the incidence of this excitatory behavior compared with continuing sevoflurane for maintenance. We conducted a randomized, single-blinded, two-period, cross-over study in 16 preschool age children undergoing repeated brief general anesthetics for eye examination. After sevoflurane induction, patients were randomly assigned to receive either sevoflurane or propofol anesthesia for maintenance. The alternative anesthetic was used for the maintenance of anesthesia on the second occasion. We compared the speed and quality of recovery characteristics of these anesthetics, as well as, overall parent satisfaction with anesthesia. Eight patients first received sevoflurane and the remaining eight patients first received propofol. Of the patients who received sevoflurane for the maintenance of anesthesia, 38% developed emergence agitation. In contrast, none developed emergence agitation when propofol was administered for maintenance of anesthesia. Despite emergence agitation, sevoflurane provided a shorter postanesthesia care unit stay than propofol. Parent satisfaction with anesthesia was greater with propofol than with sevoflurane. IMPLICATIONS: In this cross-over study, we observed the incidence of emergence agitation with sevoflurane (38%) was significantly greater than with propofol (0%) in premedicated, preschool-aged children undergoing minor noninvasive surgery.

Anesthesia Recovery Period↗

Plasma concentration of fentanyl with xenon to block somatic and hemodynamic responses to surgical incision.

BACKGROUND: Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon. METHODS: Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression. RESULTS: The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml. CONCLUSIONS: Comparing these results with previously published results in the presence of 70% nitrous oxide, the fentanyl requirement in xenon anesthesia is smaller than that in the equianesthetic nitrous oxide anesthesia.

Abdomen↗

Minimum alveolar concentration-awake of Xenon alone and in combination with isoflurane or sevoflurane.

BACKGROUND: The minimum alveolar concentration (MAC)-awake is a traditional index of hypnotic potency of an inhalational anesthetic. The MAC-awake of xenon, an inert gas with anesthetic properties (MAC = 71%), has not been determined. It is also unknown how xenon interacts with isoflurane or sevoflurane on the MAC-awake. METHODS: In the first part of the study, 90 female patients received xenon, nitrous oxide (N2O), isoflurane, or sevoflurane supplemented with epidural anesthesia (n = 36 for xenon and n = 18 per group for other anesthetics). In the second part, 72 additional patients received either xenon or N2O combined with the 0.5 times MAC-awake concentration of isoflurane or sevoflurane (0.2% and 0.3%, respectively, based on the results of the first part; n = 18 per group). During emergence, the concentration of an assigned anesthetic (xenon or N2O only in the second part) was decreased in 0. 1 MAC decrements every 15 min from 0.8 MAC or from 70% in the case of N2O until the patient followed the command to either open her eyes or to squeeze and release the investigator's hand. The concentration midway between the value permitting the first response to command and that just preventing it was defined as the MAC-awake. RESULTS: The MAC-awake were as follows: xenon, 32.6 +/- 6.1% (mean +/- SD) or 0.46 +/- 0.09 MAC; N2O, 63.3 +/- 7.1% (0.61 +/- 0.07 MAC); isoflurane, 0.40 +/- 0.07% (0.35 +/- 0.06 MAC); and sevoflurane, 0.59 +/- 0.10% (0.35 +/- 0.06 MAC). Addition of the 0.5 MAC-awake concentrations of isoflurane and sevoflurane reduced the MAC-awake of xenon to 0.50 +/- 0.15 and 0.51 +/- 0.16 times its MAC-awake as a sole agent, but that of N2O to the values significantly greater than 0.5 times its MAC-awake as a sole agent (0.68 +/- 0.12 and 0.66 +/- 0.14 times MAC-awake; P < 0.01, analysis of variance and Dunnett's test). CONCLUSIONS: The MAC-awake of xenon is 33% or 0.46 times its MAC. In terms of the MAC-fraction, this is smaller than that for N2O but greater than those for isoflurane and sevoflurane. Unlike N2O, xenon interacts additively with isoflurane and sevoflurane on MAC-awake.

Adult↗

Triolein increases microvascular permeability in isolated perfused rabbit lungs: role of neutrophils.

BACKGROUND: Pathophysiologic mechanisms of the fat embolism syndrome are poorly understood. Neutrophils are thought to play a role in the development of many forms of acute lung injury. The objective of this study was to examine the role of intrapulmonary neutrophils in lung injury resulting from fat infusion. METHODS: Triolein (0.08 mL/kg) was infused into isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pulmonary arterial pressure was monitored, and pulmonary vascular resistance and microvascular permeability (Kf) were measured at baseline and 60 minutes after triolein infusion. RESULTS: Triolein produced increases in pulmonary arterial pressure, pulmonary vascular resistance, and Kf. Neutrophil depletion or inhibition of neutrophil elastase prevented the increase in Kf after triolein, and catalase partially blocked this Kf increase. CONCLUSION: These results suggest that activated intrapulmonary neutrophils play a major role in developing triolein-induced lung injury, intrapulmonary neutrophils act chiefly via neutrophil elastase release, and reactive oxygen species are involved in the lung injury.

Animals↗