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Biomedical subjects

S Akazawa

Publications and source records attributed to S Akazawa.

At least 19 recordsLinked to original sources
PubMed1996

Long exposure to high glucose concentration impairs the responsive expression of gamma-glutamylcysteine synthetase by interleukin-1beta and tumor necrosis factor-alpha in mouse endothelial cells.

To elucidate the pathological metabolism of glutathione synthesis in diabetic endothelial cells, we studied the expression of gamma-glutamylcysteine synthetase (gamma-GCS) using a mouse vascular endothelial cell line. Exposing normoglycemic endothelial cells to tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta) increased the activity and the mRNA expression of gamma-GCS. The addition of inhibitors for nuclear factor kappaB (NF-kappaB) to the cells caused a loss of the gamma-GCS mRNA expression in response to TNF-alpha. A shift of the concentration of glucose in the medium from 5.5 to 28 mM glucose and a following incubation for 7 days decreased the expression of gamma-GCS mRNA. These cells showed no apparent responses of gamma-GCS mRNA or the activity of NF-kappaB to TNF-alpha or IL-beta. Increase in the GSH concentration of the cells treated with 28 mM glucose restored the expression of gamma-GCS mRNA and its response to TNF-alpha or IL-beta, suggesting that redox regulation is involved in the expression of gamma-GCS. In summary, the expression of gamma-GCS is regulated by TNF-alpha or IL-1beta in endothelial cells mediated by NF-kappaB stimulation, and impairment of the regulation of gamma-GCS in hyperglycemic cells may be a cause of medical complications that develop in diabetes mellitus.

Adenosine Triphosphate↗
PubMed1996

Airway management for patients with a tracheal bronchus.

A tracheal bronchus is an aberrant, accessory or ectopic bronchus arising almost invariably from the right lateral wall of the trachea, causing hypoxaemia, atelectasis, or both, during anaesthesia. We describe two patients with a tracheal bronchus found before anaesthesia. One tracheal bronchus was found by tracheobronchoscopy and the other by chest x-ray. Because of recognition of the anomaly before operation, anaesthesia was uneventful in each patient.

Anesthesia, General↗
PubMed1996

High-dose but not low-dose dexamethasone impairs glucose tolerance by inducing compensatory failure of pancreatic beta-cells in normal men.

The diabetogenic effects of glucocorticoids appear to be dose dependent. To determine the effects of different doses of dexamethasone on glucose metabolism, we performed frequently sampled intravenous glucose tolerance tests in 20 healthy young men. Glucose kinetics were analysed by the minimal model. Ten subjects received low-dose dexamethasone (2 mg/day) for 3 days, and the other 10 received high-dose dexamethasone (6 mg/day) for 3 days. The rate of glucose disappearance (KG) did not decrease in the low-dose group (2.46 +/- 0.20 to 2.19 +/- 0.11% min-1, P = 0.35). In contrast, KG in the high-dose group did decrease significantly (2.43 +/- 0.29 to 1.81 +/- 0.11% min-1, P < 0.05). The factor responsible for the decline in KG in the high-dose group was not glucose effectiveness because these values did not change in either group. The insulin sensitivity decreased significantly, by 46% in the low-dose group and 69% in the high-dose group [17.1 +/- 2.7 to 9.2 +/- 1.5 and 18.5 +/- 3.7 to 5.8 +/- 0.9 x 10(-5) min-1 (pmol/L)-1, P < 0.001 and P < 0.01, respectively]. The insulin area (0-20 min) increased significantly, by 104% in the low-dose group and 114% in the high-dose group [3412.6 +/- 609.7 to 6972.7 +/- 1450.1 and 4086.7 +/- 864.5 to 8750.0 +/- 1451.6 (pmol/L) min, P < 0.01 and P < 0.01, respectively]. Insulin sensitivity x insulin area as an estimate of insulin-dependent glucose uptake and insulin's action to suppress hepatic glucose production decreased significantly in the high-dose group (0.588 +/- 0.112 to 0.441 +/- 0.073, P < 0.05), but did not change in the low-dose group (0.436 +/- 0.050 to 0.484 +/- 0.032, P = 0.77). Therefore, the decline in KG in the high-dose group may be associated with the compensatory failure of pancreatic beta-cells against for the insulin resistance.

Adult↗
PubMed1996

[Efficacy of granisetron rescue therapy for nausea and vomiting induced by cancer chemotherapies in urogenital malignant tumor].

In this study, the usefulness of granisetron rescue therapy for nausea and vomiting induced by cancer chemotherapies, including CDDP, was examined. Granisetron was given to twenty patients with urogenital malignant tumor by iv infusion for thirty minutes after the onset of nausea or vomiting. Nausea disappeared in 15 out of 20 patients (75%), 8 of whom (40%) experienced its disappearance while the granisetron was being administered. Vomiting was perfectly controlled in 5 out of 20 patients (25%) for 24 hours after the granisetron administration. No adverse event seemingly due to granisetron was observed. The result of this study confirmed the speedy effect granisetron on nausea induced by cancer chemotherapy including CDDP, but it stopped short of demonstrating sufficient efficacy for vomiting. Prophylactic use, therefore, seems more desirable in view of the patient's QOL, when a highly emetogenic anti-tumor drug, such as CDDP, is used.

Adult↗
PubMed1995

Abundant expression of GLUT1 and GLUT3 in rat embryo during the early organogenesis period.

The developmental change of both GLUT1 and GLUT3 protein in rat embryonal and fetal brain was examined using Western blot analysis and immunohistochemistry. The brains were collected from fetuses (gestational days 10 to 20), newborn, and adult rats. On day 10, the levels of GLUT1 and GLUT3 expressions were twofold higher than those of adult levels, but thereafter decreased rapidly as the gestation progressed. The tissue distribution of GLUT1 and GLUT3 in embryo was apparently distinct. On day 10, GLUT1 was expressed in the neural tube, gut, heart and optic vesicle, while GLUT3 was expressed in the surface ectoderm and gut. Thus, high affinity glucose transporters may be required in the early organogenesis period because their energy requirement is completely dependent upon anaerobic glycolysis. GLUT3 may facilitate glucose transfer from amniotic fluid to the embryo and GLUT1 may supply glucose for use as an embryonal fuel.

Animals↗
PubMed1995

[Psychological evaluation of out-patients in our pain clinic using self-rating depression scale and state-trate anxiety inventory questionnaire].

In 98 out-patients who visited our pain clinic, we evaluated their psychological status before the first examination and one month after the treatment, using self-rating depression scale (SDS) and state-trate anxiety inventory (STAI). SDS, state anxiety, and trate anxiety scores were significantly higher in the patients with pain (trigeminal neuralgia, neck-shoulder-arm pain syndrome, lumbago and psychological pain, n = 55) compared with the patients without pain (sudden deafness and facial nerve palsy, n = 43) (P < 0.01, 0.05, 0.01). Of the patients with pain, patients with psychogenic pain showed the highest score in every test. The scores of SDS and state anxiety became significantly lower one month after the treatments compared with ones before the first examination (P < 0.01). It was considered that the decline in every score was due to the treatments in our pain clinic. In patients whose score of trate anxiety before the first examination was more than 50 points, the SDS and state anxiety showed high scores even one month after the treatments. This finding suggests that these patients need psychosomatic managements.

Adult↗
PubMed1995

Autoantibodies to glutamic acid decarboxylase in patients with autoimmune thyroid disease: relation to competitive insulin autoantibodies.

We evaluated the presence of autoantibodies to glutamic acid decarboxylase (GAD), competitive insulin autoantibodies (IAA) and islet cell antibodies (ICA) in sera from 288 non-diabetic patients with autoimmune thyroid disease (AITD), including 212 patients with Graves' disease and 76 with Hashimoto's thyroiditis, and in 235 age- and sex-matched healthy control subjects. GAD antibodies and IAA were assayed using radioimmunoassay with 125I-labelled purified pig brain GAD and human insulin, respectively. Titers of greater than 4.7 units for GAD antibodies and 50 nU/ml for IAA, respectively, the mean + 3SD of 235 age- and sex-matched healthy individuals, were defined as positive. The mean titers of GAD antibodies in patients with Graves' disease and in patients with Hashimoto's thyroiditis were 3.6 +/- 4.6 (mean +/- SD, range 0.6-52.0) units and 3.2 +/- 1.4 (range 0.6-10.0) units, respectively. Titer of GAD antibodies in patients with AITD was significantly higher than in healthy controls (P < 0.0005). Thirteen of 212 (6.1%) patients with Graves' disease and 6 of 76 (7.9%) patients with Hashimoto's thyroiditis had positive GAD antibody titers, whereas titers in healthy control sera were < 4.7 units in all but two individuals (P < 0.005). In competition analysis with purified unlabelled GAD, binding tracer was inhibited in all of 13 GAD antibody-positive Graves' sera and 5 of 6 GAD antibody-positive sera from patients with Hashimoto's thyroiditis. Eight of 212 (3.8%) patients with Graves' disease and 3 of 76 (3.9%) patients with Hashimoto's thyroiditis, but none of healthy controls had IAA levels exceeding the range for normal controls (P < 0.005). Positive IAA levels ranged between 50 and 2383 nU/ml. Strikingly, all of 19 GAD antibody-positive sera were negative for IAA. ICA were not detected in any of the patients or healthy controls. These data demonstrate that GAD antibodies in sera of AITD patients are of low titer but significantly elevated compared to healthy controls, and are independent of the appearance of IAA. They also indicate that, in patients with AITD, an autoimmune response to GAD may occur with no relationship to production of IAA.

Adult↗
PubMed1995

Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese--class II antigen and autoimmune thyroid disease.

HLA-DQA1 and DPB1 alleles were examined in relation to autoimmune thyroid disease (AITD) in the Japanese type 1 diabetic patients. The subjects consisted of 14 type 1 diabetic patients with Graves' disease, 12 patients with Hashimoto's thyroiditis and 32 type 1 diabetic patients without AITD. Comparisons were made with 35 normal controls. Among the type 1 diabetic patients with Graves' disease, the age at onset of diabetes was 31.8 +/- 14.6 years old, which was later than that of those without AITD (P < 0.01). DR9 was increased (57.1% vs. 25.9%, P < 0.05, RR: 3.85, chi 2:4.36) in the patients with Graves' disease. DQA1*0301 was increased and DQA1*0103 was decreased in the patients with Graves' disease and those without AITD. HLA-DPB1*0501 was increased (92.9% vs. 54.3%, P < 0.05, RR: 11.0, chi 2:6.57) in the patients with Graves' disease. These findings suggest the existence of a Graves' complicated subgroup characterized by the increasing association of DPB1*0501 and late onset of diabetes in Japanese type 1 diabetic patients. There exists a heterogeneity in Japanese type 1 diabetes.

Adult↗
PubMed1995

Decreased expression of the GLUT4 glucose transporter protein in adipose tissue during pregnancy.

Insulin resistance involves impaired activities of the glucose transport system in insulin target tissues. We therefore investigated the GLUT4 glucose transporter protein in adipose tissues from the pregnant women with normal glucose tolerance and from women with gestational diabetes mellitus, and compared these to nonpregnant women. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N = 6), pregnant women with normal glucose tolerance (N = 6, gestational week 38.0 +/- 0.3), and pregnant women with gestational diabetes mellitus (N = 3, gestational week 38.6 +/- 0.3). The abdominal subcutaneous adipose tissues obtained from each group were subjected to analysis of the GLUT4 glucose transporter protein. The presence of the GLUT4 glucose transporter protein in the three groups was quantitatively determined by Western blot analysis of detergent-soluble adipose tissue extracts using anti-GLUT4 antibody. GLUT4 glucose transporter protein concentration in the adipose tissue of pregnant women were significantly lower than that in nonpregnant women, and this difference was more profound in women with gestational diabetes mellitus. We demonstrated that the content of GLUT4 protein was decreased in adipose tissue from normal pregnancy compared to nonpregnant women.

Adipose Tissue↗
PubMed1995

Effects of graded infusion rates of propofol on cardiovascular haemodynamics, coronary circulation and myocardial metabolism in dogs.

We have studied the effects of a 30-min infusion of propofol 6, 9, 12, 15, 18 and 21 mg kg-1 h-1 on cardiovascular haemodynamics, coronary circulation and myocardial metabolism in 12 mongrel dogs. Mean plasma concentrations of propofol after infusion of 6 and 21 mg kg-1 h-1 increased from 2.9 (SEM 0.3) to 11.5 (0.1) micrograms ml-1. Propofol produced a progressive decrease in arterial pressure. Heart rate tended to decrease at 15, 18 and 21 mg kg-1 h-1 and cardiac index decreased significantly at infusion rates > or = 9 mg kg-1 h-1. Systemic vascular resistance tended to increase except at 21 mg kg-1 h-1 and left ventricular systolic and diastolic function were depressed. Both coronary sinus blood flow and myocardial oxygen consumption decreased in parallel with a decrease in left ventricular minute work index without producing lactate. Propofol produced progressive decreases in coronary blood flow and myocardial oxygen consumption but did not exert adverse effects on the coronary circulation.

Anesthetics, Intravenous↗
PubMed1995

Comparison of the effects of halothane, isoflurane, and sevoflurane on atrioventricular conduction times in pentobarbital-anesthetized dogs.

It is not known how sevoflurane affects the cardiac conduction system. We compared the effects of halothane, isoflurance, and sevoflurane on specialized atrioventricular (AV) conduction times in eight pentobarbital-anesthetized dogs. AV conduction times with three inhaled anesthetics at end-tidal concentrations of 1 and 2 minimum alveolar anesthetic concentration (MAC), were measured by His-bundle electrocardiography during both sinus rhythm and right atrial pacing at a slightly higher rate than sinus one. Heart rate and arterial pressure were simultaneously recorded. Halothane prolonged AV nodal conduction time during sinus rhythm (A-H interval) at 2 MAC compared with the control value, whereas isoflurane and sevoflurane did not alter the A-H interval, His-Purkinje conduction time (H-V interval), and ventricular conduction time (H-S interval) during sinus rhythm at 1 and 2 MAC. All three inhaled anesthetics did not change AV conduction times during right atrial pacing. No significant difference in AV conduction times was observed between isoflurane and sevoflurane. Heart rate during sinus rhythm remained unchanged despite a decrease in arterial pressure with three inhaled anesthetics. The property of sevoflurane and isoflurane which does not affect the cardiac conduction system may be important in the stability of the cardiac rhythm during anesthesia with these drugs.

Anesthesia, Intravenous↗
PubMed1995

Significance of glutathione depletion and oxidative stress in early embryogenesis in glucose-induced rat embryo culture.

Recent studies have demonstrated the protective effects of supplementing free oxygen radical scavenging enzymes against hyperglycemia-induced embryonic malformations. In this study, the glutathione (GSH)-dependent protection system in hyperglycemia-induced embryopathy was investigated. Rat embryos at the early head-fold stage (day 9.5) cultured in 66.7 mmol/l glucose for 48 h showed significant growth retardation and an increase in the frequency of malformations. The concentration of GSH and activity of the rate-limiting GSH-synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), significantly decreased in embryos exposed to hyperglycemia compared with controls (7.9 +/- 0.6 vs. 12.5 +/- 0.9 nmol/mg protein, P < 0.01 and 13.3 +/- 1.9 vs. 22.6 +/- 1.1 microU/mg protein, P < 0.01, respectively). Decreased activity of gamma-GCS in embryos exposed to hyperglycemia was associated with decreased expression of gamma-GCS mRNA levels. However, the activities of superoxide dismutase and glutathione peroxidase did not significantly change in these embryos. Extracellular and intracellular free oxygen radical formations estimated by Lucigenin-dependent chemoluminescence and flow cytometric analysis using 2',7'-dichlorofluorescein diacetate increased in isolated embryonic cells taken from embryos cultured under hyperglycemia. Supplementation of 2 mmol/l GSH ester into the hyperglycemic culture nearly restored GSH concentration in these embryos (11.9 +/- 0.5 vs. 12.5 +/- 0.9 nmol/mg protein) and reduced the formation of free oxygen radical species leading to almost complete normalization of growth retardation and embryonic dysmorphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Combination chemotherapy with tegafur-uracil (UFT) and cisplatin (CDDP) for advanced gastric cancer. UFTP Study Group].

An early phase II study of tegafur-uracil (UFT) combined with cisplatin (CDDP) was conducted in patients with advanced gastric cancer. UFT was administered orally for 28 consecutive days at a dose of 400 mg/m2 and CDDP was injected intravenously for 3 day at a dose of 30 mg/m2 over 8 hours every 4 weeks. This treatment cycle was repeated every 4 weeks. Sixteen patients were enrolled in this study and 14 patients could be evaluated for clinical response and toxicity. Based on the results of extramural review, 6 of 14 patients achieved a partial response and the response rate was 42.9%. High grade toxicities (WHO grade 3 or 4), specifically anorexia, nausea and vomiting, diarrhea, and leukocytopenia, were seen in 5, 2, 3 and 2 patients, respectively. The overall median survival time was 347 days (11.4 months) for evaluated patients. Although these results are preliminary, this regimen does appear to be effective in terms of tumor response and survival. Larger patient numbers in a Phase II study and further studies to evaluate survival are awaited.

Administration, Oral↗
PubMed1995

[Early phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group].

We report the results of a multicenter clinical trial comparing three combination chemotherapeutic regimens including 5-fluorouracil (5-FU) and l-leucovorin (l-LV). One hundred and twenty-two patients were randomized to three regimens comprising 5-FU (600 mg/m2) plus high-dose l-LV (250 mg/m2) in six doses given weekly by i.v. injection midway during a 2-hr infusion of l-LV (regimen A), 5-FU (370 mg/m2) plus high-dose l-LV (100 mg/m2) given simultaneously for 5 consecutive days and a 23-day interval between treatments (regimen B) and 5-FU (370 mg/m2) plus low-dose l-LV (10 mg/m2) with the same dose administration schedule as regimen B (regimen C). The response rates were 32.4% (12/37 cases) in Regimen A, 20.0% (8/40) in regimen B and 11.1% (4/36) in regimen C. The most prominent side effects observed in regimen A were diarrhea (53.8%) and leukopenia (53.8%); however, they were within permissible levels. The combinations of high-dose l-LV and 5-FU (regimen A and B) had higher response rates than that of low dose l-LV and 5-FU (regimen C). Weekly administration of high-dose l-LV and 5-FU (regimen A) is now being expanded to late phase II trials.

Aged↗