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Biomedical subjects

S Akazawa

Publications and source records attributed to S Akazawa.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1995

Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM).

Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. This assay showed that sensitivity and specificity were 83.3% and 100%, respectively. GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. GAD65 antibodies were detected in none of 25 patients with NIDDM or 25 healthy volunteers. The correlation between GAD65 antibodies and ICA, and 64K antibodies was observed to be significant (r = 0.60, P = 0.0003 and r = 0.47, P = 0.007, respectively). GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM.

Adult↗
PubMed1995

[A case of congenital hourglass bladder].

In congenital hourglass bladder, the intravesical lumen is horizontally divided into upper and lower compartments and the bladder looks like an hourglass. Most patients suffering from this disorder are adults. It occurs predominantly in men. The main symptom is inflammation of the bladder. Diagnosis has usually been made by cystography and endoscopy. The patient we report herein was a 45-year-old woman who visited us mainly due to symptoms of vesical inflammation. We performed DIP, CT, MRI, cystography and cystoscopy, and diagnosed the case as congenital hourglass bladder based on the images that were obtained. We report and discuss this case, with some information from the literature, since we believe that this is the first case of CT and MRI being performed for this condition.

Cystoscopy↗
PubMed1995

[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (internal medicine group evaluation)].

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the internal medicine departments of 24 institutions between July 1991 and May 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 53 subjects enrolled, 52 (98.1%) were eligible and 47 (88.7%) completed the scheduled treatment (AO/MF group: 23, C/MF group: 24). Although there were significant differences for age and sex between the groups, the Mantel-Haenszel test showed that these unevenly distributed characteristics did not affect the study results. The overall clinical response rates in the completed cases were 30.4% (7/23) in the AO/MF group and 16.7% (4/24) in the C/MF group. In particular, the response rate in the inoperable advanced cases with liver metastases, ascites or distant metastases was 45.5% (5/11) in the AO/MF group versus 16.7% (2/12) in the C/MF group. The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count, hemoglobin level and platelet count, nausea/vomiting, diarrhea, stomatitis, and fever. The differences in the incidence were not significant between the groups. These results show that AO-90 in combination with MF therapy is efficacious in the treatment of patients with gastric cancer.

Adolescent↗
PubMed1995

[Late phase II trial of high-dose l-leucovorin and 5-fluorouracil in advanced colorectal carcinoma. l-Leucovorin and 5-FU Study Group (Japan Eastern Group)].

A multicenter cooperative study was conducted from Dec. 1992 to April 1994 to evaluate the clinical efficacy of high-dose l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 76 patients with advanced colorectal carcinoma. Treatment consisted of intravenous bolus injection of 5-FU (600 mg/m2) 1-hour after the initiation of a 2-hour infusion l-LV (250 mg/m2), 6 weekly treatments were administered followed by a two-week rest. These treatment were repeated until progressive disease or intolerable toxicity. Seventy patients were evaluated for response. Responses were the following: PR 21, NC 29, PD 20 and the overall response rate was 30%. Grade 4 hematological side-effect was observed in three cases, and severe diarrhea in one case. These data suggested that high-dose l-LV and 5-FU was effective for advanced colorectal carcinoma but showed some hematological toxicity, and a further investigation should be carried out.

Aged↗
PubMed1995

[Spinal anesthesia for oophorectomy in a patient with pulmonary lymphangiomyomatosis accompanied by hypochondriasis].

A 41-year-old woman with pulmonary lymphangiomyomatosis had been scheduled for bilateral oophorectomy which led to amelioration of the pulmonary pathology. The discrepancy between her dyspnea on exertion and lung function tests suggested that she had a marked tendency toward hypochondria. Therefore, we chose spinal anesthesia because of its technical simplicity, rapid onset, and effectiveness of some sedatives used perioperatively. Surgery was performed uneventfully. The anesthetic method mentioned above did not worsen respiratory function perioperatively. Spinal anesthesia is thought to be appropriate anesthesia for patients with pulmonary lymphangiomyomatosis, if feasible.

Adult↗
PubMed1995

[Quality of life in patients with advanced gastric cancer receiving AO-90, a methionine-free intravenous amino acid solution, with 5-fluorouracil and mitomycin C].

We conducted a randomized, multicenter, controlled trial of AO-90, a methionine-free 7.43% intravenous amino acid solution, in patients with advanced recurrent gastric cancer. The regimen used in the study was comprised of two-week treatment cycles, with a withdrawal period between cycles. During treatment, patients were given either AO-90 (500-750 ml/day; AO/MF group) or a commercial amino acid solution (600-800 ml/day; C/MF group) by total parenteral nutrition (TPN) for 14 days concomitantly with MF therapy (5-fluorouracil 350 mg/m2/day, iv continuously for 14 days and mitomycin C 7 mg/m2, iv push on days 7 and 14). We interviewed 118 eligible and evaluable patients (72 men and 46 women; 59 cases in the AO/MF group and 59 in the C/MF group) about their quality of life immediately before the start of treatment, one week and two weeks after the start of treatment, and one week and two weeks after treatment. A 11-item questionnaire was used to interview the subjects: nine questions using a five-point scale, one question using a 100-mm linear visual analog scale, and one question using a five-grade face scale. Changes in the grades compared with baseline data were scored as 1 point (improvement of one grade or more, or 20 mm or more), 0 points (no changes), and-1 point (decline of one grade or more, or 20 mm or more). Before analyzing the significance, quality of life score data were adjusted by the Mantel-Haenszel method due to uneven distribution of subjects concerning baseline performance status and complications. Among the items questioned, subjects receiving AO-90 showed significantly higher scores in appetite, nausea, and ambulation at some evaluation time points than those receiving a methionine-containing TPN. The results show that AO-90 improved the quality of life of patients with advanced recurrent gastric cancer.

Adolescent↗
PubMed1995

[The clinical phase I study of TNP-351. The TNP-351 Research Committee].

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.

Adult↗
PubMed1995

[A randomized early phase II study of l-leucovorin and 5-fluorouracil in gastric cancer. l-Leucovorin and 5-FU Study Group].

A randomized early phase II study using l-leucovorin (l-LV) and 5-fluorouracil (5-FU) in gastric cancer was conducted. The administration schedules: Arm A was 250 mg/m2 of l-LV and 600 mg/m2 of 5-FU weekly, arm B was 100 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days, and arm C was 10 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days. PR was obtained in 10/28 (35.7%) of arm A, 7/28 (25.0%) of arm B and 0/17 (0%) of arm C, in complete cases. In eligible cases, 30.3%, 21.9% and 0%, respectively. Because there was no responder in arm C, the entry to arm C was stopped by controller at the point where 17 patients were treated with arm C. Median survival time was 9.6 months in arm A, 8.0 months in arm B and 5.9 months in arm C. Major toxicities were stomatitis, diarrhea and neutropenia. Stomatitis was seen more in arm B and C than in arm A. These data suggest that the high dose of l-LV and 5-FU seems to be a very promising combination, but there was no responder using low-dose l-LV schedule against gastric cancer. We thus selected arm A for the next late phase II study against gastric cancer.

Adenocarcinoma↗
PubMed1994

Insulin response after treatment depends on fasting plasma glucose level in NIDDM.

We investigated the relationship between the improvement in insulin secretion and glycemic control in non-insulin-dependent diabetes mellitus (NIDDM). Fifty-two patients were classified into three groups according to their pretreatment fasting plasma glucose (FPG) level: Group A, FPG < 7.8 mM, n = 20; Group B, 7.8 mM < or = FPG < 11.1 mM, n = 17; and Group C, 11.1 mM < or = FPG, n = 15. A 75-g oral glucose tolerance test (OGTT) and a glucagon loading test were performed to evaluate insulin secretion before and after treatment. Plasma glucose levels during a 75-g OGTT were decreased significantly after treatment in all groups (P < 0.01). In Group A, there was no significant change in insulin secretion before and after treatment (1466 +/- 213 pM to 1565 +/- 191 pM, P = 0.35). In contrast, in Groups B and C, insulin secretion was poor and suppressed initially, but increased significantly when good glycemic control was obtained after treatment (respectively, 587 +/- 70 pM to 863 +/- 79 pM, P < 0.01, and 621 +/- 94 pM to 1236 +/- 232 pM, P < 0.01). The degree of improvement in insulin secretion in 75-g OGTT correlated positively with the degree of improvement in FPG level after treatment (r = 0.5, P < 0.001). However, the C-peptide response to glucagon did not change before and after treatment. In conclusion, impaired insulin secretion recovered by the good glycemic control in NIDDM with FPG levels above 7.8 mM. Therefore, strict glycemic control (FPG below 7.8 mM) seems important for maintaining good insulin secretion.

Adult↗