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Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 469 records · Page 26Linked to original sources
PubMed1992

Long-lasting tolerance of articular cartilage after experimental intraoperative radiation in rabbits.

In experimental intraoperative irradiation, 18 adult rabbits received a single, 50-Gy dose of x-radiation at a unilateral knee joint, and subsequent changes in the articular cartilage were examined over a 15-month period by histology, scanning electron microscopy, and autoradiography. Although the subchondral bone showed histologically typical findings of osteonecrosis three to nine months postirradiation, the articular cartilage revealed no obvious degenerative changes during the entire study period. Scanning electron microscopy revealed normal collagen architecture in the irradiated cartilage for as long as 15 months postirradiation. Autoradiography demonstrated active RNA synthesis by the irradiated chondrocytes during the same period. These results indicate that articular cartilage tissue tolerates intraoperative radiotherapy without sustaining serious degenerative changes, unless possible collapse or contracture disturbs its biomechanical integrity. The survival of articular cartilage can be advantageous for this type of limb-salvage surgery in the treatment of malignant bone tumors around a synovial joint.

Animals↗
PubMed1992

Effects of human recombinant IL-1 on d-tubocurarine-induced histamine release from isolated rat peritoneal mast cells.

The relationship between d-tubocurarine (d-Tc) and human recombinant interleukin-1 (rIL-1) was studied on the histamine-releasing property of isolated rat peritoneal mast cells. d-Tc induced histamine release in a dose-dependent manner (1 x 10(-4) M-3 x 10(-3) M) from isolated rat mast cells. Human rIL-1 (0.3-10 ng/ml) potentiated the d-Tc-induced histamine release and shifted the dose-response curve to left without changing the maximum histamine release by d-Tc. The potentiation by human rIL-1 was completely blocked by anti-IL-1-antibody. Human rIL-1 neither released histamine nor affected IgE-related histamine release in isolated rat peritoneal mast cells. Human recombinant IL-2, IL-3, and tumour necrosis factor neither released histamine from isolated rat mast cells nor affected d-Tc-induced histamine release. These results suggested that human rIL-1 might hypersensitize d-Tc receptors distributed on plasma membrane of rat mast cells.

Animals↗
PubMed1992

Effects of fermentation on product consistency.

A variety of different fermentation processes has been successfully employed to produce consistent protein-based biopharmaceuticals from genetically engineered animal cells. Chinese hamster ovary (CHO) cells were genetically modified to produce recombinant human soluble CD4, tissue plasminogen activator (tPA) or erythropoietin (EPO). Soluble CD4 was collected from extended perfused fermentations of several months' duration, during which some quantitative loss of DNA copy level, mRNA expression level, and fermentation titer were observed. In one extended run, a novel contaminant appeared in intermediates purified from later harvests. However, in all cases, the final soluble CD4 product was consistent in terms of purity and potency. Evaluation of genetic stability for tPA examined both biological traits at the cellular level as well as potency, purity and structure of product derived from cells at various levels of in vitro age; no significant cell age effects were observed. Similarly, evaluation of the EPO product showed that genetically-determined and process-determined traits such as potency, tryptic peptide mapping, and sialylation were consistent from lot to lot. These data exemplified how process design, process validation, and in-process and quality control assays can be used effectively to ensure the consistency of recombinant products derived from cell culture fermentations.

Animals↗
PubMed1992

Measurement of synovial fluid volume: a new dilution method adapted to fluid permeation from the synovial cavity.

A new dilution method was developed to measure the synovial fluid (SF) volume in a single knee joint of a rabbit. In this dilution method, we used 2 different kinds of dextrans, one having a mean molecular weight (M(r)) of 487,000 and labelled with fluorescein isothiocyanate (FITC) as a marker, and the other M(r) of 300,000 to give hypertonicity to the solution. By employing these high M(r) dextrans in their optimal concentrations, we were able to minimize the inevitable transsynovial shift of the fluid and marker after intraarticular injection. The original SF volume was then calculated using the fluorescence intensities of the injected and retrieved fluids. By determining the accurate volume of SF, it became possible to measure per joint the protein and hyaluronic acid contents in SF as well as the total and differential cell counts. The results obtained by this new method were reasonable and consistent, except for volume, with the reported results based on pooled samples from multiple joints. We believe that the method can contribute to the analysis of SF changes under various conditions in small laboratory animals.

Animals↗
PubMed1992

Studies on teratological testing using chicken embryos--effects of solvents, injection sites and the age of the embryo.

The purpose of this study was to examine the effects of solvents, injection sites and embryo age when using chicken embryos for teratological testing. The results obtained were as follows: 1) Solvents: distilled water, physiological saline, sesame oil, 25% ethanol, 0.5% carboxymethylcellulose and 0.1% methylcellulose solution were not toxic in Day-4 embryos (eggs incubated for 4 days). 2) With 6-aminonicotinamide, air space injection more effectively induced malformations in chicken embryos. With boric acid, however, yolk sac injection was better. It was shown therefore that the appropriate injection site varied according to the test drug. 3) 6-aminonicotinamide induced characteristic malformations when injected into embryos of various ages ranging from 4 to 13 days of incubation. On the other hand, boric acid was teratogenetic only when injected into Day-3 or Day-4 embryos. It seems, therefore, that the age of the embryo at the time of administration is of critical importance and that the optimum time of administration varies according to the test drug.

6-Aminonicotinamide↗
PubMed1992

[A study of complications of hepatic arterial infusion catheter].

We studied complications of the infusion catheter, which were implanted in the hepatic artery under laparotomy, and then connected with an implantable infuser port in patients with hepatocellular carcinoma (n = 32) and metastatic liver tumor (n = 11). Infuse-A-Port catheter was used for 31 cases (A group), and Anthron P-U catheter for 12 cases (B group). In B group, the cannulation method was changed; the catheter was placed in the hepatic artery via the gastroduodenal artery, which was ligated and cut to prevent kinks in the catheter. In the A group, 17 cases (54.8%) showed complications such as dislocation of the catheter tip (7 cases) including penetrating duodenal ulcer (2 cases), arterial occlusion (6 cases), injury of catheter (2 cases) and occlusion of the infuser port (2 cases). One case, however, having a fistula between the hepatic artery and the duodenum, died of sudden massive bleeding. In the B group, 3 cases (25.0%) showed complications such as dislocation of the catheter tip (1 case) and arterial occlusion (2 cases). The catheter in B group lasted longer than that in A group. Thus, our cannulation technique using Anthron P-U catheter may decrease the catheter complications.

Catheters, Indwelling↗
PubMed1992

[Changes in plasma sulfoconjugated catecholamines during perioperative period of cardiac operations--effect of continuous infusion of dopamine].

In order to clarify the physiological significance of sulfate conjugation of catecholamines and the effect of continuous dopamine infusion on the conjugate formation, we measured the plasma levels of free and sulfoconjugated catecholamines during the perioperative period of cardiac operations. The study group consisted of 12 adult patients who underwent cardiac operations. There were 13 study intervals starting from a day before each operation to 72 hours after each operation for the collection of blood specimen. The plasma levels of free and sulfoconjugated catecholamines were measured by radioenzymatic assay. The plasma levels of free dopamine did not show significant change by the induction of anesthesia, but they increased rapidly after the start of dopamine infusion to the level of 7654.9 +/- 731.7 pg/ml. Thereafter, the plasma free dopamine levels remained steady during the 24 hours after operation at 7516.7 pg/ml to 8449.2 pg/ml. On the other hand, the plasma levels of conjugated dopamine increased progressively by dopamine infusion during the 24 hours after operation. The plasma levels of free adrenaline increased significantly to the level of 1049.5 +/- 117.7 pg/ml by dopamine infusion, and lasted with plateau until the 24th hour after operation at the range of 1076.8 pg/ml to 1218.9 pg/ml. Conjugated adrenaline followed a similar pattern to that of conjugated dopamine, with a progressive increase due to the infusion of dopamine. In the case of noradrenaline, free noradrenaline started to increase at the time of cardiopulmonary bypass and showed a further increase by dopamine infusion during the first hour after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Immunosuppression in patients with Barrett's esophagus.

BACKGROUND: Patients with Barrett's esophagus have a higher incidence of esophageal cancer than has the general population. Local tissue injury and exposure to carcinogens presumably play a role in malignant transformation, but the possibility of altered host immune surveillance must also be considered. METHODS: The level of immunoreactivity was investigated in six healthy control subjects; 14 patients with gastroesophageal reflux, seven with and seven without esophagitis; and nine patients with Barrett's esophagus. Parameters studied were (1) T-cell and B-cell function with mitogen-stimulated lymphocyte blastogenesis, (2) immunosuppressive properties of autologous serum, and (3) interleukin-2 production by peripheral blood mononuclear cells. Nutritional status as a possible cause for immunosuppression was assessed by measurement of serum albumin, transferrin, and prealbumin. RESULTS: Patients with Barrett's esophagus had a significant suppression of all T-cell (p less than 0.01) and B-cell function (p less than 0.01) and interleukin-2 production (p less than 0.001) when they were compared to the controls. Interleukin-2 production was also reduced significantly compared to that in patients with gastroesophageal reflux with and without esophagitis (p less than 0.05). No differences were observed in serum immunosuppression or nutritional factors. CONCLUSIONS: Although the immunosuppression observed in the patients with Barrett's esophagus was milder than that found in other immunocompromised states, it may be sufficient to encourage the malignant transformation of Barrett's mucosa.

Adult↗
PubMed1992

[A case of adenosquamous carcinoma with unknown origin and with superior vena cava syndrome as the first symptom].

This report is concerning a case of adenosquamous carcinoma having unknown origin and showing SVC syndrome as the first symptom. A 44 year-old man was admitted to our hospital because of facial edema at the beginning of April 1990. He was diagnosed as having a mediastinal tumor of the SVC syndrome type. Resection of the SVC tumor and part of the pericardium was performed on June 20, 1990. The operation had extraordinary findings. Lymph nodes adhering to tumor invaded the adjacent right side of the trachea and were situated in a rosette-like form. Furthermore, a part of the tumor stemmed into the lumen of the superior vena cava causing complete obstruction. The pathological diagnosis of the SVC tumor was adenosquamous carcinoma, however, no clinical examinations could identify its original matrix. Mediastinal tumors of unknown origin are reported as about 1% of all mediastinal tumors, and are responsible for 0.68% of all carcinomas in the mediastinum. This was one experience of a rare case of mediastinal tumor having unknown origin and showing SVC syndrome as the first symptom.

Adenocarcinoma↗
PubMed1991

Metabolic rate of membrane-permeant diacylglycerol and its relation to human resting T-lymphocyte activation.

DL-1,2-Dioctanoylglycerol (1,2-DiC8) added to human peripheral resting T lymphocytes was rapidly metabolized to produce octanoic acid and further to small molecules, probably by the action of diacylglycerol lipase and/or nonspecific esterase. Only a small portion was converted to the corresponding phosphatidic acid or was isomerized to 1,3-DiC8 before being metabolized. The uptake of 1,2-DiC8 by the cell was apparently fast, and the rate of disappearance of 1,2-DiC8 was dependent on the cell densities; at a higher density of T lymphocytes 1,2-DiC8 was removed quickly, whereas at a lower cell density 1,2-DiC8 remained for a longer period of time. With a fixed amount of 1,2-DiC8 added, the extent of interleukin 2 receptor alpha-subunit (IL-2R alpha) expression was inversely related to the cell density and proportional to the duration of exposure of the cells to 1,2-DiC8. Repeated doses of 1,2-DiC8 potentiated IL-2R alpha expression. In contrast, a single dose of phorbol 12-myristate 13-acetate caused T-lymphocyte activation to similar extents irrespective of the cell density, probably because the phorbol ester was not metabolized and remained in membranes. The available evidence supports a proposal made in a previous paper and indicates that the sustained activation of protein kinase C for at least the first 3-4 hr is essential for the activation of resting T lymphocytes.

Biological Transport↗
PubMed1991

Mechanism of palytoxin-induced Na+ influx into cultured bovine adrenal chromaffin cells: possible involvement of Na+/H+ exchange system.

To elucidate the mechanism of palytoxin (PTX)-induced Na+ influx, we examined the effect of amiloride, an inhibitor of Na+/H(+)-antiporter, on PTX-induced Na+ influx into cultured bovine adrenal chromaffin cells in relation to its effects on Ca2+ influx and catecholamine secretion. Amiloride dose-dependently inhibited PTX-induced 22Na+ influx, whereas tetrodotoxin (TTX) had no effect. Amiloride also inhibited PTX-induced Na(+)-dependent 45Ca2+ influx and catecholamine secretion. PTX alone did not significantly affect the intracellular pH, but it decreased in the presence of PTX and amiloride. These results indicate that an amiloride-sensitive Na+/H+ exchange mechanism is probably involved in PTX-induced, TTX-insensitive Na+ influx that triggers Ca2+ influx and catecholamine secretion from the cells.

Acrylamides↗
PubMed1991

Lysophosphatidylcholine as a possible second messenger synergistic to diacylglycerol and calcium ion for T-lymphocyte activation.

An immediate reaction product of phosphatidylcholine hydrolysis catalyzed by phospholipase A2, lysophosphatidylcholine (lysoPC), synergizes with a membrane-permeable diacylglycerol, 1,2-dioctanoylglycerol, and ionomycin to activate resting T-lymphocytes as measured by interleukin-2 alpha-receptor expression. It is suggestive that both phospholipase C and phospholipase A2 are directly involved in signal transduction in a synergistic fashion and that lysoPC acts as an additional second messenger for cellular regulation, probably for long-term responses such as cell proliferation and differentiation.

Calcium↗
PubMed1991

Characterization of palytoxin-induced catecholamine secretion from cultured bovine adrenal chromaffin cells. Effects of Na(+)- and Ca(2+)-channel blockers.

The effect of palytoxin (PTX), a potent marine toxin, on catecholamine (CA) secretion from cultured bovine adrenal chromaffin cells was examined. PTX at concentrations of over 10(-10) M induced CA secretion concentration-dependently. About 40-50% of the total cellular CA was secreted during 20-min incubation with 3 x 10(-8) M PTX. PTX-induced CA secretion was dependent on both extracellular Na+ and Ca2+. PTX caused increases in [22Na](+)- and [45Ca](2+)-influxes into the cells. Increase in [22Na](+)-influx was observed at concentrations of over 10(-11) M PTX and was maximal at 10(-10) M PTX and then gradually decreased at higher concentrations that induced [45Ca](2+)-influx and CA secretion. On the other hand, increase in [45Ca](2+)-influx was observed at concentrations of over 10(-10) M PTX and increased with increase in concentration of PTX. This concentration-response curve for PTX-induced [45Ca](2+)-influx was similar to that for PTX-induced CA secretion. The CA secretion and [22Na](+)- and [45Ca](2+)-influxes induced by PTX were not affected by tetrodotoxin (TTX), but were significantly inhibited by quinidine and aprindine(mexiletine), antiarrythmic drugs known to block Na(+)-channels. Ca(2+)-channel blockers such as nifedipine, verapamil, Co2+, Cd2+, inhibited both CA secretion and [45Ca](2+)-influx induced by PTX. These results indicate that PTX-induced CA secretion is mediated by activation of Na(+)-dependent, TTX-insensitive voltage-dependent Ca(2+)-channels, and is inhibited by quinidine and aprindine through their inhibitory effects on the Na(+)- and Ca(2+)-influxes into the cells induced by PTX.

Acrylamides↗
PubMed1991

Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications.

Kinetic properties of the purified alpha, beta, and gamma subspecies of protein kinase C (PKC) to respond to diacylglycerol, phosphatidylserine (PtdSer), and Ca2+ were reinvestigated in the presence of several fatty acids. Although responses of these enzyme subspecies to the lipids slightly differed from one another, the reaction velocity of these subspecies was significantly enhanced by synergistic action of diacylglycerol and a cis-unsaturated fatty acid. Arachidonic, oleic, linoleic, linolenic, and docosahexaenoic acids were active in this role, whereas saturated fatty acids such as palmitic and stearic acids were inactive. Elaidic acid was also inactive. In the presence of both PtdSer and diacylglycerol, the cis-unsaturated fatty acids increased further an apparent affinity of PKC to Ca2+ and allowed the enzyme to exhibit almost full activation at nearly basal levels of Ca2+ concentration. The concentration of fatty acid giving rise to the maximum activation of enzyme was approximately 20-50 microM. The result presented herein implies that the receptor-mediated release of unsaturated fatty acids from phospholipids may take part, in synergy with diacylglycerol, in the activation of PKC even when the Ca2+ concentration is low. A possibility arises, then, that the activation of PKC is an integral part of the signal-induced degradation cascade of various membrane phospholipids, which is initiated by the actions of phospholipase C and phospholipase A2.

Arachidonic Acid↗