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Biomedical subjects

S Akazawa

Publications and source records attributed to S Akazawa.

At least 127 records · Page 7Linked to original sources
PubMed1990

Plasma lipid transfer activities in hyper-high-density lipoprotein cholesterolemic and healthy control subjects.

The relationships between plasma lipid transfer protein (LTP) activity and various lipid or lipoprotein concentrations were studied in 14 hyper-high-density lipoprotein (hyper-HDL) cholesterolemic subjects and 152 healthy controls. We measured plasma LTP activity by our sensitive assay method, using radiolabeled proteoliposomes as the lipid donor, low-density lipoprotein (LDL) as the acceptor, and a very small amount of untreated plasma (typically 1 to 2 microliters) as the sample. Control subjects had the mean of LTP activity at 206 +/- 45 nmol/mL/h. The difference of LTP activity between men and women was not statistically significant. In the control subjects, the activity of plasma LTP had a significantly positive correlation with the concentrations of total cholesterol (r = .639, P less than .01) and LDL cholesterol (r = .634, P less than .01), but not with those of HDL cholesterol and total triglyceride, nor with percent ideal body weight. One of 14 patients with hyper-HDL cholesterolemia had no detectable LTP activity, and three others had very low LTP activity. From these data, LTP activity may be one of the important factors to influence plasma LDL concentration, and the lack of LTP activity may be related to a subclass of hyper-HDL cholesterolemias.

Adult↗
PubMed1990

Comparison of islet cell antibodies, islet cell surface antibodies and anti-bovine serum albumin antibodies in type 1 diabetes.

The present study was undertaken to compare the changes in islet cell antibodies (ICA), islet cell surface antibodies using rat insulinoma cells (RINr-ICSA), and anti-bovine serum albumin antibodies (BSA-Ab) in the clinical course of type 1 (insulin-dependent) diabetes. Sera were obtained from 57 patients with type 1 diabetes and 47 normal controls. ICA, RINr-ICSA and BSA-Ab were detected by an enzymatic immunohistochemical method, an indirect immunofluorescence method and an enzyme-linked immunosorbent assay, respectively. The incidence of ICA significantly decreased with the duration of diabetes: less than 1 year: 5/6 (83%); 1-2 years: 3/6 (50%); 2-3 years; 2/6 (33%); greater than 3 years 6/39 (15%). There was a significant positive correlation between RINr-ICSA and BSA-Ab (P less than 0.05). These findings suggest that RINr-ICSA or BSA-Ab may be produced by some similar immune mechanism which is, however, different from ICA, and that they have no direct relation to the clinical course of diabetes.

Adolescent↗
PubMed1990

[High-dose leucovorin and 5-fluorouracil in advanced gastric and colorectal cancer. High-Dose Leucovorin and 5-FU Study Group].

A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation.

Adult↗
PubMed1990

[Biliary and pancreatic excretion of methotrexate (MTX) and 5-FU on the MTX/5-FU sequential therapy].

On the postoperative adjuvant MTX/5-FU sequential therapy, biliary and pancreatic excretion of both drugs was studied through the hepatic and pancreatic drainages in pancreatoduodenectomized patients. MTX: 100 mg/m2 of bolus injection and 5-FU: 800 mg/m2 of sequential one hour drip infusion were used in this series. Biliary excretion of MTX was reached peak concentration at 90 min, its mean value being 5 fold of serum concentration. During the observation period of 4.5 hours, the recovery of MTX in bile was calculated as 3-12% which presumed to be more because of still continuing biliary excretion on the terminal observation. Pancreatic excretion of MTX was minimal and not so as to have further clinical meaning. Though the serum concentration of 5-FU was raised up with its infusion, biliary and pancreatic outputs of 5-FU were small, each value showing one third compared with at a single shot of the same doses. From the obtained mode and time lag of concentration curves of both drugs, the rationale of per oral and earlier administration of Leucovorin was discussed as a possible way of removal of MTX from intestine.

Adult↗
PubMed1989

The influence of ventricular extrasystoles and postextrasystoles on cardiovascular dynamics in anesthetized dogs.

The influence of ventricular extrasystoles and postextrasystoles on cardiovascular dynamics were assessed in terms of maximum rate of rise of left ventricular pressure (max dP/dt), ascending aortic flow, left ventricular stroke volume, and left ventricular end-diastolic transverse dimension in anesthetized dogs. A single ventricular extrasystole, two and three consecutive ventricular extrasystoles (couplet and triplet) were induced by applying mechanical stimulation to the surface of the right ventricule. In any of these ventricular extrasystoles, max dP/dt, stroke volume and end-diastolic transverse dimension were decreased, compared with those in preceding sinus beats, i.e., pre-extrasystoles. Over the several postextrasystoles, max dP/dt was increased and gradually returned to its control level. This increase in max dP/dt, i.e., postextrasystolic potentiation paralleled an increase in ascending aortic peak flow but did not always bring about an increase in stroke volume, even when a left ventricular contraction was initiated by a significantly greater end-diastolic transverse dimension. The postextrasystolic potentiation seems to be associated with the Frank-Starling mechanism and does not compensate for the decreased in stroke volume elicited by the ventricular extrasystoles. In conclusion, not only ventricular extrasystoles per se but also postextrasystoles exert the adverse influence on cardiovascular dynamics consecutively.

Journal Article↗
PubMed1989

Changes of serum thyroid hormone levels induce malformations on early embryogenesis in rats.

The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternal-fetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed on 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period.

Animals↗
PubMed1989

Effects of brief exposure to insulin-induced hypoglycemic serum during organogenesis in rat embryo culture.

We have previously shown that long-term exposure to medium containing insulin-induced hypoglycemic serum during the early phase of organogenesis can adversely affect embryonic development in rat embryo culture and that these effects were mediated through the interruption of glycolytic flux that constituted the principal pathway at this embryonic stage. Further experiments were performed to examine whether brief exposure to the hypoglycemic medium during critical developmental periods would have adverse effects on embryogenesis during embryo culture not only in normal but also in high glucose concentrations. Rat embryos in the early head-fold stage (9.5 days gestation) were grown in vitro for 48 h until neural tube closure occurred; dysmorphogenic lesions were not elicited in either the basal culture medium containing 6.6 mM glucose (control medium) or the hyperglycemic medium supplemented with glucose at a concentration of 33.3 mM. Hypoglycemic mediums (2.2-2.5 mM glucose) were prepared from the serum of rats given insulin intraperitoneally. Postimplantation embryos (in early neural tube formation) were briefly exposed (1 h) to hypoglycemic medium on day 10.3 of gestation during the basal culture. After exposure to the hypoglycemic medium for 1 h during culture in the control medium, embryos showed minor growth retardation and dysmorphogenic lesions (7.1% open neural pores). Exposure to the hypoglycemic medium for 1 h during culture in hyperglycemic medium suplemented with a subteratogenic concentration of glucose (33.3 mM) resulted in greater growth retardation and increased occurrence of dysmorphogenic lesions (17.3% open neural pores).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[A case of hepatocellular carcinoma (HCC) with lung metastasis which responded to chemotherapy with a single use of 1-hexylcarbamoyl-5-fluorouracil (HCFU)].

To our knowledge, there has been only one report pertaining to the efficacy of HCFU for treatment of metastatic lung lesion of HCC, so we reported a case of HCC with lung metastasis which responded to chemotherapy with a single use of HCFU. A 64-year-old male was diagnosed as having HCC with lung metastasis by biochemical examination, abdominal CT, hepatic arteriogram and chest X-P. He had been treated previously with gamma-interferon and mitoxantrone, which were assessed as NC and PD, respectively. Two months after last chemotherapy, HCFU was administrated at a dose of 400 mg/body everyday for 8 months. After 4 weeks metastatic lung lesions showed remarkable regression (47% decrease) and disappeared completely 9 weeks later. The size of primary liver tumor gradually decreased during therapy and revealed marked improvement (85.7% decrease) after about 2 months of this therapy. During these periods serum levels of alpha-fetoprotein dropped from 430 ng/ml to less than 10 ng/ml. He is presently still alive and the duration of the PR attained to 35 weeks. As side effects, hypoproteinemia, anorexia and hot sensation were observed.

Antineoplastic Agents↗
PubMed1989

[Randomized multicenter trial of sequential methotrexate and 5-fluorouracil versus 5-fluorouracil alone in advanced gastric cancer].

In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.

Adult↗
PubMed1989

[Effects of acute hypoxia on cardiovascular dynamics, myocardial metabolism and ECG in dogs].

In pentobarbital-pancuronium anesthetized open chest dogs, left ventricular pressure (LVP), first derivative of LVP (dp/dt) and left ventricular end-diastolic pressure (LVEDP) were measured by a micromanometer tipped catheter, stroke volume and cardiac output (CO) by an electromagnetic flow meter and coronary sinus blood flow (CSBF), by a thermal dilution catheter, respectively. Mean arterial pressure (mAP), mean pulmonary arterial pressure (mPAP), lead II of ECG and esophageal temperature were monitored. Blood gas, catecholamines and lactate of arterial blood and coronary sinus blood were measured and myocardial lactate extraction ratio (MCL) was calculated. As an index of contraction, maximum positive dp/dt (+dp/dt max), and as an index of relaxation, the time constant (T) of isovolumic left ventricular pressure fall were employed, respectively. Acute hypoxia was induced by the inhalation of a 5% O2-95% N2 gas mixture and arterial blood oxygen pressure was maintained between 15 and 20 mmHg. Along with the advancement of hypoxia, +dp/dt max, CO and mAP gradually increased and peaked in 5 minutes. Thereafter, these parameters began to decrease and CO fell to zero in 20 minutes. mPAP and HR slowly increased and peaked in 9 and in 12 minutes, respectively. T was progressively prolonged throughout the hypoxia. CSBF/CO ratio was increased and stayed at a high level even after CO began to decrease. MCL decreased and changed from positive values to negative ones in 5 minutes. Epinephrine and norephinephrine concentrations slowly increased and peaked in 16 minutes. A gradual decrease in the R wave, shortening of the R-R interval and lengthening of the QTc interval were observed in ECG. This study indicated that the left ventricular relaxing function was impaired earlier than contracting function by acute hypoxia and that conversion of the augmented left ventricular contractile state to the depressed one coincided with conversion of myocardial lactate extraction to its production.

Acute Disease↗
PubMed1988

Effects of sevoflurane on cardiovascular dynamics, coronary circulation and myocardial metabolism in dogs.

The effects of 2.5% and 5% of sevoflurane anesthesia on hemodynamics and myocardial metabolism were studied in pentobarbital-pancuronium anesthetized dogs. The interaction between nicardipine and 2.5% sevoflurane was also examined. Sevoflurane produced dose-dependent ( P << 0.05 to P << 0.01) decreases in systolic arterial pressure (SAP), heart rate (HR), cardiac index (CI), left ventricular minute work index (LVMWI), maximum rate of rise of left ventricular pressure (LV dP/dt), the time constant of fall in isovolumic left ventricular pressure (T) and systemic vascular resistance (SVR), whereas stroke volume index (SVI) and left ventricular end-diastolic pressure (LVEDP) remained unchanged. Central venous pressure (CVP) was significantly ( P << 0.05) increased at 5%. Myocardial oxygen consumption (MV(O)(2)), and myocardial lactate extraction ratio (ML ext) were decreased in a dose-dependent manner ( P << 0.05). Myocardial oxygen extraction ratio (M(O)(2) ext) was significantly ( P << 0.01) decreased at 5%. The ratio of the left ventricular minute work index to myocardial oxygen consumption (LVMWI/MV(O)(2)), i.e., left ventricular efficiency was significantly decreased only at 5% ( P << 0.05). Coronary sinus blood flow (CSBF) was significantly ( P << 0.05) decreased only at 2.5% sevoflurane and coronary vascular resistance (CVR) was significantly ( P << 0.01) decreased only at 5% sevoflurane. The ratio of CSBF to CO (CSBF/CO) showed a tendency to increase as sevoflurane concentrations were increased. Nicardipine (0.01 mg.kg(-1)) administered intravenously under 2.5% sevoflurane caused significant ( P << 0.05 to P << 0.01) decreases in SAP, HR, LV dP/dt, SVR, and CVR, and increases in CVP, SVI, CI, and CSBF ( P << 0.05 to P << 0.01). CSBF/CO remained unchanged. MV(O)(2), M(O)(2) ext, and ML ext were significantly ( P << 0.05 to P << 0.01) decreased. LVMWI/MV(O)(2) showed a tendency to increase. It is concluded that sevoflurane causes a rapidly and easily controlled cardiovascular depression and may not have unfavorable effects on coronary circulation and myocardial metabolism. Nicardipine exerts a synergistic myocardial depressant effect on sevoflurane, in terms of both cardiovascular dynamics and myocardial metabolism.

Journal Article↗
PubMed1988

The effect of verapamil on halothane-epinephrine or digitalis-induced ventricular dysrhythmias in dogs.

The effect of verapamil on ventricular dysrhythmias was evaluated using two canine models. In one model, ventricular dysrhythmias were induced by 1% halothane-epinephrine (1.5 approximately 30 micro g/kg/min.) in 20 dogs (Group I). In the other model, ventricular dysrhythmias were induced by digoxin (0.1 approximately 0.2 mg/kg) in 27 dogs (Group II). Verapamil (0.2 approximately 0.5 mg/kg) was given to treat these ventricular dysrhythmias. When verapamil was ineffective, lidocaine (1 approximately 2 mg/kg) was given following the administration of verapamil. In 7 dogs of group II, lidocaine alone was given. Verapamil was effective in 16 animals of group I, and in 10 animals of group II. Lidocaine was ineffective in the remaining 4 of group I, whereas effective in the remaining 17, including those given lidocaine alone of group II. From these findings, it was inferred that Ca(2+) dependent abnormal automaticity and/or re-entry may be more closely related to the genesis of halothane-epinephrine-induced ventricular dysrhythmias refractory to lidocaine, whereas triggered activity may be more closely related to that of digitalis-induced ventricular dysrhythmias. In conclusion, verapamil was more effective against halothane-epinephrine-induced ventricular dysrhythmias than against digitalis-induced ventricular dysrhythmias.

Journal Article↗
PubMed1988

Antibodies against saline-soluble components of skeletal muscle in myasthenia gravis.

Antibodies against phosphate-buffered-saline extracts (SE) of non-acetylcholine receptor (AChR) skeletal muscle antigens were found in patients with myasthenia gravis (MG). The antigenicity of SE was distributed in three fractions with molecular masses of over 200 kDa, 90-150 kDa and 7-14 kDa on gel filtration. These fractions shared common antigenicities. Further analysis of 90-150 kDa fractions on sodium dodecyl sulphate polyacrylamide gel electrophoresis showed five major bands, ranging from 105 kDa to 275 kDa. The antibodies against SE were detected in 52% (58/112) of the MG patients; incidence and titres were higher in the thymoma group (n = 21; 90% and 0.872 respectively) than in the non-thymoma group (n = 91; 43% and 0.200, P less than 0.001). In patients without a thymoma, these antibodies were frequently observed in late-onset disease and the severe generalized form (P less than 0.01). In 4 of 7 ocular MG patients without anti-AChR antibodies, low but appreciable levels of anti-SE antibodies were found. In 73% (11/15) of generalized MG patients treated with prednisolone and thymectomy, anti-SE antibody titres changed in association with those of anti-AChR antibodies and with the clinical course. Both antibody titres increased synchronously in patients who developed crises.

Adult↗
PubMed1988

[Antitumoral effect of gamma-interferon in patients with hepatocellular carcinoma].

The antitumoral effect of gamma-Interferon (Re-IFN-gamma, KW-2202) on nine patients with hepatocellular carcinoma (HCC) has been investigated. gamma-IFN was administered intravenously biweekly at a dose of 8-24 x 10(6) units/day for 5 consecutive days. As all patients had measurable disease determined by an abdominal CT, the antitumoral effect was evaluated by CT, according to the criteria of Koyama and Saito, During gamma-IFN therapy, one patient, who received a total of 4.4 x 10(8) units of gamma-IFN, achieved a partial response (PR) 133 days after onset of treatment. Another patient showed a minor response (MR) 43 days after start of therapy. The duration of the PR and MR were 7.8 weeks and 10.8 weeks, respectively. Two patients were assessed as having had no change (NC), and 5 patients as still manifesting a progressive disease (PD). Marked falls in serum alpha-fetoprotein levels during therapy were observed in 2 cases of which one was graded as having obtained a PR, and the other, a NC. The toxicities observed were fever, general malaise, headaches, and joint pains, which were slight and transient in most cases. In one case, however, a therapy was stopped because of a continuous and severe shoulder pain with no metastasis. Further studies on the use of IFN, possibly in combination with other chemotherapeutic agents, should be performed in patients with HCC.

Aged↗
PubMed1988

[The role of thymidylate synthetase in sequential dose of MTX and 5-FU in the advanced scirrhous type gastric cancer].

The biochemical rationale for the potentiation of the effects of 5-FU by MTX is based on an increased PRPP level or MTX polyglutamate produced by MTX. The cytotoxic action of MTX results not only from inhibition of DHFR but also depends upon thymidylate synthetase (TS), a key enzyme in DNA synthesis. We obtained a monoclonal antibody to TS using a hydrophilic peptide consisting of 20 amino acids in the TS amino acid sequence and demonstrated by PAP that TS was detectable in poorly differentiated adenocarcinoma cells but not in well differentiated adenocarcinoma cells. Upon clinical application of sequential doses of MTX and 5-FU, the median survival durations were 318 days and 156 days for scirrhous-type gastric cancer patients and non-scirrhous-type gastric cancer patients respectively. These results suggest that immunohistochemistry with TS antibody is available as an indicator of the effect of this drug regimen.

Adenocarcinoma, Scirrhous↗