[Terminal care. II. Easing of symptoms of cancer patients. 5. Management of adverse effects of antineoplastic agents].
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Antineoplastic Agents↗
Biomedical subjects
S Akazawa
Publications and source records attributed to S Akazawa.
Adenosine 3',5'-cyclic monophosphate mimics the inhibitory effect of high glucose on MAP kinase phosphorylation in rat mesangial cells.
Alteration in mesangial cell function induced by high glucose levels is implicated in the development of diabetic nephropathy. The aim of this study was to investigate the mechanism by which high glucose attenuates mesangial cell proliferation. Thymidine incorporation in cultured mesangial cells decreased in the presence of high glucose concentrations in a dose dependent manner, with the maximum decrease of 25% occurring at a glucose concentration of 55.5 mM. Phosphorylation of mitogen-activated protein (MAP) kinase was abolished when the cells were treated with 55.5 mM glucose compared with 11.1 mM glucose. The concentration of intracellular cAMP doubled in the presence of 55.5 mM glucose. The addition of 8Br-cAMP (1.0 mM) to the culture media containing 11.1 mM glucose decreased thymidine incorporation by 34%, similar to the effect of high glucose. In order to clarify the contribution of protein kinase A (PKA) to the MAP kinase cascade, we used PKA inhibitor (H-8). The addition of H-8(10 microM) recovered MAP kinase phosphorylation in the presence of 55.5 mM glucose. Our data indicated that the inhibition of this mitogenic pathway mediated by activation of PKA, which is probably induced by high glucose levels, may play an important role in the perturbation of mesangial cells.
Animals↗
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↗
Clinical evaluation of non-insulin-dependent diabetes mellitus patients with autoantibodies to glutamic acid decarboxylase.
We evaluated the frequency of antibodies to glutamic acid decarboxylase (GAD-Ab) in Japanese patients diagnosed initially as having non-insulin-dependent diabetes mellitus (NIDDM) and investigated a possible link between the presence of GAD-Ab and development of the insulin-dependent (ID) state. The population sample consisted of 583 Japanese NIDDM patients (age at onset > 30 years) who were initially non-ketotic and did not require insulin treatment during at least 6 months of observation. GAD-Ab were measured using radioimmunoassay. The clinical characteristics of GAD-Ab+ patients were carefully examined at four-year intervals from the onset of diabetes. We also examined the ID state by measuring the level of postprandial serum C-peptide and i.v. glucagon-stimulated serum C-peptide. The overall prevalence of GAD-Ab in Japanese NIDDM patients was 3.8%. The frequency of GAD-Ab+ did not significantly decrease with a long history of diabetes. GAD-Ab+ patients had a lower body mass index, compared with GAD-Ab- (20.8 +/- 2.9 vs 23.0 +/- 3.7, P < 0.005), lower postprandial C-peptide levels (0.7 +/- 0.6 vs 1.4 +/- 1.2, P < 0.01), and an early commencement of insulin therapy (3.6 +/- 4.7 vs 8.3 +/- 6.6, P < 0.01). GAD-Ab+ patients who had already developed the ID state had characteristically higher titers of GAD-Ab (421.4 +/- 359.1) and a higher frequency of islet cell antibodies (ICAs) (77.8%), compared with GAD-Ab+ NID patients (titer: 60.2 +/- 86.9, P < 0.005, 23.1%, P < 0.05, respectively). GAD-Ab+ ICAs+ patients showed higher frequencies of ID state at any diabetic duration compared with GAD- ICAs-, while GAD-Ab+ ICAs- patients did not differ in the frequency of the ID state from GAD- ICAs-. Our results suggest that the presence of both GAD-Ab and ICAs represents a high risk for IDDM in GAD-Ab+ NIDDM patients.
Adult↗
TNF-alpha stimulates glucose uptake in L6 myoblasts.
The mechanism of TNF-alpha to regulate glucose metabolism remains unclear. To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I.
Animals↗
Detection of recombinant GAD65 and GAD67 antibodies using a simple radioimmunoassay.
Autoantibodies to glutamic acid decarboxylase (GAD) are useful diagnostic and predictive markers for Type 1 (insulin-dependent) diabetes mellitus. In the present study we describe a development of simple, reproducible, and quantitative radioimmunoassays for detecting GAD65 and GAD67 antibodies, and compare sensitivity and specificity of these assays with native GADAb radioimmunoassay. We used in vitro transcribed and translated recombinant human islet GAD65 and GAD67 as antigens, and anti-human IgG was used to separate free from antibody-bound ligand. By using these assays, GAD65Ab and GAD67Ab were detected in 65% and 25% of recent-onset Japanese patients with Type 1 diabetes, respectively, but none of 71 healthy control subjects tested were postive for GAD65Ab and GAD67Ab. Moreover, none of 48 patients with other autoimmune disease had GAD65Ab or GAD67Ab. There was a 100% correlation between the sensitivity and specificity of GAD65Ab assay and native GADAb assay. GAD65Ab and GAD67Ab were concordant in 28% of Type 1 diabetic sera and the levels of GAD65Ab in doubly positive patients were significantly higher than those in only GAD65Ab positive patients (P < 0.01). GAD65Ab are specific markers for Type 1 diabetes, and the radioimmunoassay using in vitro translated GAD and anti-human IgG, which is sensitive, convenient and low cost for detecting GAD antibodies, will facilitate large population screening of Type 1 diabetes.
Adult↗
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↗
Atrioventricular conduction during adenosine-induced hypotension in dogs anaesthetized with sevoflurane.
We have studied the effects of adenosine-induced hypotension on A-H interval (atrioventricular (AV) nodal conduction time during sinus rhythm), St-H interval (intra-atrial plus AV nodal conduction time during atrial pacing), H-V interval (His-Purkinje conduction time) and H-S interval (total ventricular conduction time) by His-bundle electrocardiography in addition to surface electrocardiogram during both sinus rhythm and atrial pacing in nine dogs anaesthetized with 1 MAC of sevoflurane. Stepwise increases in infusion rates of adenosine to 0.1, 0.3, 0.5 and 1.0 mg kg-1 min-1 produced a dose-related decrease in mean arterial pressure from 91 (6) to 38 (2) mm Hg. Adenosine significantly increased the A-H interval at infusion rates of 0.5 mg kg-1 min-1 and above, and the St-H interval at 1.0 mg kg-1 min-1. The H-V and H-S intervals remained unchanged. Heart rate decreased significantly only at 1.0 mg kg-1 min-1 with a significant increase in the PR interval. Adenosine-induced hypotension did not have deleterious effects on AV conduction times and the surface electrocardiogram in dogs anaesthetized with 1 MAC of sevoflurane. This may indicate that the effects of adenosine on AV conduction were small and therefore are unlikely to be a contraindication to the use of adenosine for inducing hypotension in patients with initially normal conduction during sevoflurane anaesthesia.
Adenosine↗
Unrecognized migration of an entire guidewire on insertion of a central venous catheter into the cardiovascular system.
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Aged↗
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↗
[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↗
[Analysis of clinical effects of a concurrent CDDP/5-FU therapy on inoperable colon cancer].
The mechanisms of synergic effects on cancer cells, the rational dose schedules resulting from these action mechanisms, and actual clinical results for inoperable colon cancer patients by a concurrent CDDP/5-FU therapy, are described. We analyzed the clinical results on the basis on the literature dealing with concurrent CDDP/5-FU therapy for inoperable colon cancer patients. This analysis suggested that some modified dose schedules of CDDP and 5-FU for inoperable colon cancer patients made no difference in response rates, survival times or adverse effects. Concurrent low-dose CDDP/5-FU therapy for inoperable colon cancer patients is now awaited in Japan.
Antineoplastic Combined Chemotherapy Protocols↗
[Cesarean section in a morbidly obese parturient under epidural anesthesia].
A 26-yr-old morbidly obese parturient with a body mass index of 62 kg.m-2 underwent elective cesarean section for preeclampsia under epidural anesthesia. The distance between the skin and the epidural space was about 9 cm at the L3-4 interspace via mid approach. Epidural catheter was inserted 5 cm cephalad in the sitting position and a bolus of 17 ml of mepivacaine 1.5% was given in the supine position. The T5 level of analgesia was obtained 10 min later. Forty minutes after the start of the surgery, a female newborn weighing 3,206 g was delivered with an Apgar score 8 at 1 min and 9 at 5 min. Throughout the surgery, sufficient analgesia was obtained and any complications such as severe hypotension and respiratory depression did not develop. Postoperative pain was relieved sufficiently with a continuous epidural infusion of 0.25% bupivacaine at a rate of 0.5 ml.h-1 for two days. Both maternal and neonatal postpartum courses were uneventful. In conclusion, elective cesarean section in a morbidly obese parturient was successfully managed with epidural anesthesia. This indicates that an elective cesarean section under epidural anesthesia reduce the risk of perioperative complications in a morbidly obese parturient.
Adult↗
The death of biomedical journals.
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Computer Communication Networks↗
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↗
[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↗
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↗
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↗