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Biomedical subjects

K Akazawa

Publications and source records attributed to K Akazawa.

At least 181 records · Page 10Linked to original sources

Chemosensitivity differences between primary and metastatic lesions of clinical gastric cancer.

An in vitro chemosensitivity test, the succinate dehydrogenase inhibition (SDI) test, was used to examine 16 pairs of samples obtained simultaneously from primary and metastatic lesions of clinical gastric cancer. Concerning the metastases, 11 were in the lymph nodes and five in the liver. The chemosensitivities of metastatic lesions against six anti-tumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), and 5-fluorouracil (5-FU), differed from those in the primary lesions, and there were no correlations of chemosensitivities between the primary and the metastatic lesions against these drugs, except for DDP. The lymph nodes were more sensitive to CQ, ADM, MMC, DDP, ACR and 5-FU, while the liver was less sensitive than the primary lesions to CQ, ADM, MMC, DDP, and ACR. Our findings indicate that in patients with lymph node metastasis, there is a sensitivity to anti-tumour drugs, while in cases of liver metastasis, drug treatment may be less effective. We propose that chemosensitivity testing should be done when attempting to design anti-tumour drugs.

Antineoplastic Agents↗

Prediction of the prognosis of liver cirrhosis in Japanese using Cox's proportional hazard model.

Data on 155 patients with liver cirrhosis were analyzed, using Cox's proportional hazard model. Twenty variables were screened, using a multiple linear regression analysis in a stepwise manner and 6 were considered to reflect the prognosis of cirrhotics. Three of the 6 variables were significantly prognostic, i.e. ascites, atrophy of the right lobe of the liver seen on liver scintigram and the concentration of serum albumin. The prognostic index (PI) for each patient was calculated by adding all the products of scores of these three variables with the corresponding coefficient: PI = 0.895 X ascites (absent = 0, present = 1) + 0.983 X atrophy of right lobe of the liver on the liver scintigram (absent = 0, present = 1) + (-0.561) X serum albumin (g/dl). According to the PI, the subjects were separated into three groups; group 1: PI less than -1.9, group 2: -1.9 less than or equal to PI less than -0.6, group 3: PI greater than or equal to -0.6. The global 5- and 10-year survival rates of each group were 80% and 65% in group 1, 50% and 30% in group 2 and 12% and 0% in group 3, respectively. Four of the 14 deaths in group 1, 8 of 47 in groups 2 and 10 of 24 in group 3 were caused by hepatocellular carcinoma. Our observations suggest that advanced stage cases of cirrhosis are at a high risk concerning development of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Clinical features of intractable epilepsy in Japanese children.

The clinical features of refractory epilepsy were studied in comparison between 135 patients in a refractory group and 103 in a controlled group. All the children were Japanese. The clinical features of the refractory group were the onset of epilepsy during the first year of life, absence of family history, retarded development before the onset, phakomatoses, daily or weekly seizures, secondarily generalized epilepsy, and marked EEG abnormalities at the initial visit, a change of types in epilepsy, no improvement in EEG findings, mental deterioration or severe retardation during the follow-up. The number of drugs was increased and relatively new drugs such as carbamazepine, valproic acid or clonazepam were frequently administered. The side effects, including gum hypertrophy, drowsiness, hypertrichosis, ataxia or increased serum-GTP, were more frequent in the refractory group.

Age Factors↗

Effects of the encircling procedure on the aqueous flow rate in retinal detachment eyes: a fluorometric study.

Fluorophotometry was carried out in nine cases of unilateral non-traumatic rhegmatogenous retinal detachment successfully treated by a combination of local buckling and an encircling procedure with a silicone band. After topical instillation of fluorescein the change in its concentration in the anterior chamber was followed, from which the loss rate of the dye from the anterior chamber (k0) and the cornea-aqueous transfer coefficient (kc.ca) were estimated. The thickness of the cornea and the anterior chamber volume were also measured, and the aqueous flow rate and the corneal endothelial permeability were calculated in individual eyes. The examinations performed 4-18 months after operation showed that the aqueous flow rate in the operated eye fell to 85 (SD 12)% of that in the fellow control eye (p less than 0.005). In the operated eye the anterior chamber volume also fell significantly, and the corneal endothelial permeability may have decreased. Ocular hypotension after the detachment surgery with encirclement was attributable to a decrease in the aqueous flow rate.

Adult↗

Further purification and characterization of acid-stable protease inhibitor from ascites of an ovarian carcinoma patient.

An acid-stable protease inhibitor (AS-PI) has been previously demonstrated in ascitic fluid from patients with ovarian carcinoma. In this study, the AS-PI was further purified using DEAE-cellulose and isoelectric focusing (IEF), and a partial characterization was undertaken. On DEAE-cellulose ion-exchange column chromatography, AS-PI activity was observed in both adsorbed and non-adsorbed fractions. The former represented the main AS-PI peak. By IEF, the respective pI values were 1.6 and 4.5. By gel filtration, the molecular weight of the main (adsorbed fraction) AS-PI was 78 000. This AS-PI strongly inhibited trypsin and to a lesser extent chymotrypsin, but exerted no inhibitory effect on plasmin. It slightly inhibited SH proteases such as papain and ficin. Immunologically, AS-PI was distinct from alpha 1-antitrypsin, alpha 1-antichymotrypsin, inter-alpha-trypsin inhibitor, antithrombin III, C1-inactivator, alpha 2-macroglobulin and alpha 2-plasmin inhibitor. The main AS-PI reacted with and was neutralized by antiurinary trypsin inhibitor serum, and on immunoelectrophoresis, had a mobility slightly cathodal to serum albumin.

Adult↗

Marked increase of plasma acid stable/soluble trypsin inhibitor in hemodialysis patients.

The activity of acid stable/soluble trypsin inhibitor (ASTI) was found to be considerably elevated in the plasma of hemodialysis patients (80.3 +/- 24.6 U/ml; 21-fold higher than normal). The increased ASTI was a very acidic compound (pI = 1.66) with a molecular weight (Mr) of 55000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunological identity of the ASTI to urinary trypsin inhibitor was confirmed.

Adolescent↗

Acid stable protease inhibitor in ascites of ovarian carcinoma.

In patients with ovarian tumors, a novel protease inhibitor which is very stable in acid (AS-PI, acid stable protease inhibitor) was identified in the ascites and tumor fluid as well as in the urine and plasma. The highest AS-PI activity was observed in the tumor fluid of ovarian carcinomas (10.7 +/- 2.3 U/ml), followed by the ascites of ovarian carcinomas (8.2 +/- 4.2 U/ml). There was a significant difference in activity of the tumor fluid and ascites between malignant and benign tumors (p less than 0.005, p less than 0.05, respectively). The same antigenicity of AS-PI fractionated from ascites of ovarian carcinomas to urinary trypsin inhibitor was identified by double immunodiffusion and neutralization techniques. It migrated in the serum albumin fraction on immunoelectrophoresis. By gel filtration, the AS-PI in the ascites of ovarian carcinomas showed a molecular weight of 70000-80000. Two active components with molecular weights of 61300 +/- 2100 and 73300 +/- 2500 were detected by SDS polyacrylamide gel electrophoresis.

Chromatography, Gel↗

Multiple molecular forms of acid-stable plasmin inhibitor derived from human urinary trypsin inhibitor.

It was found that cyanogen bromide (BrCN) treatment of the highly purified human urinary trypsin inhibitors (H-UTI; specific activity 1,897 U/mg protein, and L-UTI; specific activity 1,850 U/mg protein) readily produced new plasmin inhibitors with almost no loss of UTI activity. Five multiple forms of chemically cleaved inhibitors (UTIB-I, UTIB-II, UTIB-III, UTIB-IV and UTIB-V) could be isolated from BrCN-treated L-UTI by isoelectric focusing and gel filtration. These inhibitors were very acid-stable and their isoelectric points (pI) were 4.5, 4.6, 4.9, 5.1 and 6.4, respectively. The molecular weights by SDS-polyacrylamide gel electrophoresis were almost the same at about 23,000 +/- 3,000. Although these inhibitors showed both anti-plasmin and anti-trypsin activities, much higher anti-plasmin/anti-trypsin activities were observed in the cleaved inhibitors than in the parent UTI. They competitively inhibited human plasmin with Ki values of 3.0-4.1 X 10(-8) mol/l (H-D-Val-Leu-Lys-pNA substrate).

Antifibrinolytic Agents↗

Localization of fibrinolytic activity in ovulation of the rat follicle as determined by the fibrin slide method.

The localization and changes of fibrinolytic activity during the process of ovulation were investigated by the fibrin slide method. In regular estrous cycle rats, fibrinolytic activity first appeared in the external area of the follicle wall (stigma) at 12 hr before ovulation. No activity was noted in the follicular cavity at this time. A peak of activity was seen at 2 hr before ovulation. After ovulation, the activity decreased markedly. The activity was completely inhibited on fibrin slides to which 10(-2) M trans-aminomethyl-cyclohexane carboxylic acid had been added. No activity was observed on plasminogen-free fibrin slides. These results suggest that fibrinolytic activity is one of the important factors involved in the rupture of the mature follicle wall, and that the fibrinolytic activity is due to plasminogen activator activity.

Animals↗

Modulation of reflex activity of motor units in response to stretch of a human finger muscle.

Changes in stretch reflex responses were examined in two types of motor task, force control and position control, by applying a small quick stretch to the middle finger extensor digitorum communis (EDC) muscle at an unpredicted time and observing activities of single motor units. Subjects were asked to maintain a constant extending isometric force at the metacarpophalangeal (MP) joint for force control, and to maintain a constant middle finger position against an applied force for position control. No significant differences in the tonic activities of EDC motor units were seen between the two types of motor task when the same force was exerted about the MP joint. Tonic activities of the EDC muscle and its antagonists were thus similar for both types of motor task. Ten of the eighteen motor units investigated showed obvious reflex responses (increase in firing rate) with latencies of 30-60 msec after the stretch. This reflex response was greater for position control than for force control, given the same operating conditions of tonic force, finger position, and activities of motor units. Enhancement of the stretch reflex for position control was also observed in surface electromyograms of the same muscle.

Adult↗

Production of plasminogen activator in a melanoma cell line.

A melanoma cell line (Bowes) was found to produce plasminogen activator even on its growing phase, and the rate of plasminogen activator production was rather constant. The production of plasminogen activator was proportional to the cell number. Morphologically, no specific features for plasminogen activator production were seen. Plasminogen activator was observed in the lysate of this cell line only when the cell number was large. The extracellular plasminogen activator activity was higher than the intracellular plasminogen activator activity, suggesting the existence of a secretion mechanism for the plasminogen activator.

Cell Count↗

The role of plasminogen activator in ovulation.

The role of plasminogen activator in ovulation was investigated using the inhibitor, trans-aminomethylcyclohexane carboxylic acid (t-AMCHA). In the regular cycle rat, the plasminogen activator activity of the follicles increased from the diestrus to the estrus phase. In the latter phase, a proteolytic enzyme which was not inhibited by t-AMCHA appeared. After ovulation, the plasminogen activator activity decreased. When ovulation was induced in immature rats by pregnant mare serum gonadotrophin and human chorionic gonadotrophin, remarkable fibrinolytic activity appeared in the ovaries immediately before ovulation. When t-AMCHA was given in the ovulation-induced rats, the fibrinolytic activity of the ovaries was suppressed, the number of ovulated ova decreased and the timing of ovulation was delayed. When t-AMCHA solution was given to rats in the proestrus phase, ovulation was almost completely suppressed, but aprotinin solution exerted no effect on ovulation. These results suggest that plasminogen activator is a key enzyme in ovulation, and that the chain reaction from plasminogen activator to proteolytic enzyme (including collagenase) is of greater importance than that of plasminogen activator to plasmin.

Animals↗