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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 217 records · Page 12Linked to original sources

Effect of YM294, recombinant human interleukin-11, on carboplatin-induced thrombocytopenia in rats.

We investigated the effects of YM294, recombinant human interleukin-11, on changes in blood cell levels in carboplatin-treated rats. Continuous infusion of YM294 was carried out by either intravenous or subcutaneous injection (10 and 100 micrograms/rat/day) for 14 days via an implanted osmotic pump. Carboplatin (30 mg/kg iv) significantly decreased platelet counts on days 7-9; counts subsequently increased to levels greater than the initial level by day 21. Intravenous administration of YM294 inhibited this decrease in platelet count by carboplatin and increased the platelet count in the recovery phase in a dose-dependent manner. YM294 also showed effects on carboplatin-induced changes in white blood cell and red blood cell counts; these effects seemed, however, to be neither consistent nor dose-dependent. The effects of YM294 on subcutaneous infusion were similar to those on intravenous infusion. The effect of YM294 on the survival of rats treated with a higher dose of carboplatin (60 mg/kg iv) was also investigated. YM294 (100 micrograms/rat/day) given by continuous intravenous infusion increased the 30-day survival rate. These results confirm the utility of YM294 in the treatment of thrombocytopenia after chemotherapy.

Animals↗

Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-I tax gene.

To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular gene expression and its relation to tumorigenesis, two lines of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome were produced. The transgene was expressed in many organs, including the brain, salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that the expression of the c-fos and c-jun genes, but not of the lyn and c-myc genes, was augmented 2- to 20-fold in histologically normal skin and muscle of these mice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three to seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also activated in these tumors. The possible roles of elevated c-fos and c-jun gene expression in tumorigensis are discussed.

Animals↗

Attenuation of the catecholamine response to tracheal intubation with oral clonidine in children.

We conducted a prospective, randomized, double-blind , controlled clinical trial to examine (1) whether plasma catecholamine (CA) concentrations increased in response to tracheal intubation in children, and (2) the effects of clonidine on the CA responses. Sixty children (ASA physical status I) aged 7-13 yr were allocated to one of three groups (n = 20 for each group): diazepam 0.4 x kg(-1) (active control), clonidine 2 micrograms x kg(-1), or clonidine 4 micrograms x kg(-1) po. These agents were administered 105 min before induction of anaesthesia followed by oral atropine 0.03 mg x kg(-1) given 60 min before anaesthesia which was induced with thiamylal 5 mg x kg(-1) and tracheal intubation was facilitated with vecuronium 0.2 mg x kg(-1). Laryngoscopy, lasting 30 sec, was attempted two minutes after administration of the induction agents. Serial values for blood pressure, heart rate, and venous plasma CA concentrations were compared among the three groups and with the respective preinduction measurements. Children receiving diazepam or clonidine 2 micrograms x kg(-1) showed remarkable increases in systolic and diastolic blood pressures, heart rate, and plasma CA concentrations in response to tracheal intubation (P < 0.05). The increases were similar for the two regimens. These haemodynamic and CA changes were smaller in children receiving clonidine 4 micrograms x kg(-1) (P < 0.005). The haemodynamic responses were positively correlated with the CA responses. These findings indicate that tracheal intubation following rapid sequence induction of anaesthesia in children provokes a reflex increase in sympathetic activity characterized by increased plasma CA concentrations, and that attenuation of the cardiovascular changes with a high oral dose of clonidine may be due to suppression of the increase in sympathetic activity evoked by the intubation.

Adolescent↗

Oral clonidine premedication reduces vomiting in children after strabismus surgery.

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.

Administration, Oral↗

Lansoprazole reduces preoperative gastric fluid acidity and volume in children.

The purpose of this study was to explore the efficacy of lansoprazole, a proton pump inhibitor, in reducing the acidity and volume of gastric aspirate in children immediately following the induction of anaesthesia. One hundred healthy in-patients aged 3-11 yr undergoing elective surgery were randomly allocated to four groups (n = 25 each): lansoprazole-lansoprazole, placebo-placebo, placebo-lansoprazole, and lansoprazole-placebo. For each treatment regimen, the first medication was administered at 9:00 pm on the night before surgery and the second at 5:30 am on the morning of the day of surgery (three hours preoperatively). The dose of lansoprazole was 30 mg (approximately 1.4 mg.kg-1 mean). Children were offered 10 ml.kg-1 apple juice three hours before induction of anaesthesia. After induction of anaesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube and analyzed for pH and total fluid volume. Lansoprazole increased gastric fluid pH and decreased gastric fluid volume regardless of whether it was administered before or after placebo. Two consecutive doses of lansoprazole was the most effective means of increasing the pH and reducing the volume of gastric aspirate; in this group, there were no subjects with gastric aspirate volume > 0.4 ml.kg-1 and pH < 2.5. Oral lansoprazole, at least 30 mg, given on the night before surgery or on the morning of surgery will improve the gastric environment at the time of induction of paediatric anaesthesia. The most effective regimen was two doses (at bedtime and on the morning) of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Gastric fluid volume and pH after nizatidine in adults undergoing elective surgery: influence of timing and dose.

We conducted a prospective, randomized, double-blind study to investigate the effect of oral nizatidine (150-600 mg), a new potent H2 antagonist, on preoperative gastric fluid pH and volume in adults undergoing elective surgery. One hundred and seventy-five healthy adults (21-68 yr) were randomly allocated to seven treatment groups (n = 25); Placebo was administered at 21:00 and 06:30 the night before and on the day of surgery, respectively (0/0: control); nizatidine 150 mg at 21:00 and placebo at 06:30 (150/0); placebo at 21:00 and nizatidine 150 mg at 06:30 (0/150); nizatidine 150 mg at 21:00 and 06:30 (150/150); nizatidine 300 mg at 21:00 and placebo at 06:30 (300/0); placebo at 21:00 and nizatidine 300 mg at 06:30 (0/300); and nizatidine 300 mg at 21:00 and 06:30 (300/300). Each patient fasted overnight and took the drug and/or placebo with 20 ml water. After induction of anaesthesia, the pH and volume of gastric fluid obtained through an orogastric tube were measured. The mean pH of 0/150, 150/150, 300/0, 0/300, and 300/300 groups was higher than that of the control group (P < 0.05). Gastric volume in these groups was smaller than in the control (P < 0.05). The 150/0 group failed to decrease gastric fluid volume and increase pH. In the 300/0 group, the gastric pH was lower than other regimens which effectively decreased gastric acidity (P < 0.05). The number of patients with a pH < 2.5 and a volume > 0.4 ml.kg-1 in the 0/150, 150/150, 0/300, and 300/300 groups (0%) was less than in the control group (16%) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Improvement of the accuracy of references in the Canadian Journal of Anaesthesia.

A previous study indicated that there were many citation errors in the Canadian Journal of Anaesthesia. After this report, editors of the Journal requested any contributors, whose papers were accepted for publication, to verify the accuracy of reference citation by including a photocopy of the first page of each reference. The present study examined if the accuracy of the reference list had improved. We compared citation errors between volumes of 1990 and 1994. One hundred references from each year's publication were randomly selected. After citations of nonjournal articles were excluded, the remaining 190 citations were carefully scrutinized. Authors' names, article title, journal title, volume number, page numbers, and year were examined in each selected reference. A reference was deemed correct if each element of the citation was identical to its source. Of the examined references, 48% and 22% contained one or more errors in 1990 and 1994, respectively. Errors in the title and author field of citation were most common in the either of the two years, occurring in about 70% of the references which contained some errors. Citation errors in Canadian Journal of Anaesthesia were considerably improved after the request to verify citation accuracy. Although this check-system probably contributes to the improvement of accuracy of reference citation, the rate of citation errors remains high. We believe that contributors' efforts will enhance the value of the journal.

Anesthesiology↗

Isolation and characterization of neutralizing monoclonal antibodies to human vascular endothelial growth factor/vascular permeability factor121 (VEGF/VPF121).

We have established monoclonal antibodies (MAbs) against human vascular endothelial growth factor/vascular permeability factor121 (VEGF/VPF121). Two (MV101 and MV303) of the 28 MAbs neutralized the mitogenic activity of VEGF/VPF121 on human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. Both of the MAbs reacted to VEGF/VPF121 and also VEGF/VPF165 with somewhat different binding properties in a sandwich-type enzyme-linked immunosorbent assay (ELSIA). The binding of MV101 and MV303 to VEGF/VPF121 was competitive, but MV415, another anti-VEGF/VPF121 MAb without neutralizing activity, did not complete with either of the antibodies. MV101 and MV303 specifically recognized the native form of VEGF/VPF121 and VEGF/VPF165 in Western blotting. They did not react with VEGF/VPF when the antigens were fractionated under reducing conditions. These observations suggested that MV101 and MV303 might recognize the epitopes closely located on the configuration of VEGF/VPF121 molecule and the epitopes recognized by MV101 and MV303 may play an important role in the VEGF/VPF-receptor signal transduction. These MAbs significantly suppressed the growth of a human hepatoma, PLC/PRF/5, in vivo.

Animals↗

Effects of exogenous intravenous glucose on plasma glucose and lipid homeostasis in anesthetized infants.

BACKGROUND: Whether intravenous glucose administration to infants during anesthesia is necessary remains to be resolved. The current study was designed to investigate the effect of exogenous glucose infusion on plasma glucose and lipid homeostasis in infants undergoing minor surgery. METHODS: Sixty infants (inpatients, ASA physical status 1) between 1 and 11 months of age were divided randomly into three groups as follows: LR group, lactated Ringer's solution (LR) alone; D2LR group, 2% glucose in LR; and D5LR group, 5% glucose in LR. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. All fluids were infused at a rate of 6 ml.kg-1.h-1 until 1 h after surgery. Plasma concentrations of glucose, nonesterified fatty acids, ketone bodies, insulin, and cortisol were determined at induction of anesthesia, at the end of surgery, and 1 h after surgery. RESULTS: No infants in the three groups had hypoglycemia (< 50 mg.dl-1) throughout the study. In the LR group, plasma glucose concentration remained unchanged perioperatively compared with the basal values (at induction), whereas in the D2LR group, it increased during surgery but remained normoglycemic. In the D5LR group, plasma glucose concentration increased markedly both during and after surgery. In 6 of 20 infants, plasma glucose was greater than 200 mg.dl-1 at the end of surgery. In 8 of 20 infants receiving glucose-free infusion, plasma glucose concentrations decreased at the end of surgery. In contrast, the plasma glucose concentration increased in infants receiving glucose infusion. In the LR group, plasma concentrations of nonesterified fatty acids and ketone bodies increased at the end of and after surgery, suggesting lipid mobilization. The base excess decreased in the LR groups as concentration of the ketone bodies increased. Plasma insulin concentrations increased in the D2LR and D5LR groups and decreased after surgery in infants receiving a glucose-free solution. No intergroup differences in plasma cortisol concentrations existed at any sample point. CONCLUSIONS: These data indicate that, in otherwise healthy infants undergoing minor surgery, intravenous infusion of 2% glucose may be sufficient to maintain plasma glucose concentrations within physiologic ranges and to prevent a compensatory increase in lipid mobilization (lipolysis) when fluids are infused at a rate of 6 ml.kg-1.h-1. However, there are limitations in extrapolating the results to neonates.

Anesthesia↗

Paralysis caused by acute myelitis in Theiler's murine encephalomyelitis virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord.

Intravenous infection by Theiler's murine encephalomyelitis virus strain GD VII causes acute encephalomyelitis and paralysis in infected mice. However, nude mice and cyclophosphamide-treated ddY mice did not show paralysis when they were able to survive until day 20 post-infection (p.i.). Of ddY mice infected with 5 x 10(7) p.f.u./mouse, 70-80% showed symptoms of paralysis on day 20 p.i. The viral titres in the brain and spinal cord in infected mice were not significantly different between paralytic and non-paralytic mice. In all of the mice infected with the virus, CD4+ lymphocytes and CD8+ lymphocytes had infiltrated the brain on days 10, 12, 14 and 20 p.i. as demonstrated by flow cytometric analysis. In contrast, few T lymphocytes infiltrated the spinal cord in the non-paralytic mice. Administration of an anti-CD4 monoclonal antibody (MAb) or anti-T cell receptor-alpha beta MAb on day 6 p.i. inhibited paralysis until day 20 p.i., though 20% of the MAb-treated mice and 80% of the control mice showed paralysis. Administration of anti-CD8 MAb was not effective in the suppression of paralysis. The MAb treatment did not significantly augment viral replication in the spinal cord, although the viral titres in the brain of the MAb-treated mice increased significantly. After the transfer of spleen cells from infected C3H mice, the recipient mice infected with a small amount of the virus showed paralysis, though uninfected mice did not. This transfer could be blocked by CD4+ lymphocyte depletion of the donor mice. These results indicate that paralysis caused by acute myelitis in Theiler's virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord.

Acute Disease↗

CD3+/TCR-alpha beta- cells are important in protecting spinal cord tissues against Theiler's virus strain GD VII infection.

Intravenous infection with Theiler's virus strain GD VII causes acute encephalomyelitis in mice. Endogenous IFN-gamma produced in the spinal cord is important to protect the tissue in mice infected with this virus. Neither CD4+ cells nor CD8+ cells infiltrated the spinal cords of infected mice until Day 9 postinfection. However, the number of CD3+/TCR-gamma delta+ cells increased in the spinal cords of mice infected with the virus. These cells resided in the spinal cords of normal mice, and produced IFN-gamma as a result of stimulation by immobilized anti-CD3 mAb. Elimination of CD3+ cells by the administration of a specific mAb augmented viral replication and suppressed production of endogenous IFN-gamma. Depletion of TCR-alpha beta+ cells and ASGM1+ cells did not affect the viral replication, and did not alter the production of IFN-gamma. Therefore, CD3+/TCR-alpha beta- cells producing IFN-gamma play an important role in the protection of the spinal cord against Theiler's virus infection. These results suggest that CD3+/TCR-alpha beta- cells might be identical to TCR-gamma delta+ cells.

Animals↗