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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 325 records · Page 18Linked to original sources
PubMed1991

Decreased expression of the myristoylated alanine-rich C kinase substrate in transformed BALB/C 3T3 mouse fibroblasts.

Expression of the myristoylated alanine-rich C kinase substrate was studied in the untransformed A31 and the transformed BPA31, DA31 and KA31 BALB/c 3T3 mouse fibroblast cell lines. The MARCKS transcript was markedly reduced in the three transformed cell lines. Southern analysis revealed similar gene copy number and no apparent DNA rearrangement. In the untransformed A31 cells, the MARCKS mRNA was constitutive in the cell cycle.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Tumor necrosis factor-beta in the serum of adult T-cell leukemia with hypercalcemia.

Serum tumor necrosis factor-beta (TNF-beta) from patients with adult T-cell leukemia (ATL) was studied by a sandwich enzyme-linked immunosorbent assay (ELISA) developed in our laboratory using biotinylated monoclonal anti-TNF-beta and recombinant TNF-beta. Seven of eight patients with hypercalcemia showed elevation of serum TNF-beta. On the other hand, TNF-beta could not be detected by the ELISA in 28 patients without hypercalcemia. The lower detection limit in this assay was 100 pg/mL, corresponding to 500 pg/mL by the conventional method. In two patients serum TNF-beta level decreased after treatment in association with the level of serum calcium. Furthermore, immuno-staining using anti-TNF-beta and avidin-biotin complex showed the presence of cytoplasmic TNF-beta in not only human T-cell leukemia virus type I infected cell lines, but also freshly isolated cells from ATL patients with hypercalcemia. The actual biologic activity of TNF-beta in serum was confirmed by a conventional bioassay in a patient with hypercalcemia, and its cytotoxic activity was inhibited by the addition of anti-TNF-beta antibody in the assay. These results suggested that serum TNF-beta might be one of the factors contributing to the hypercalcemia, at least in patients with ATL.

Adult↗
PubMed1991

Binding characteristics of a new 1,5-benzothiazepine, clentiazem, to rat cerebral cortex and skeletal muscle membranes.

The binding properties of a new 1,5-benzothiazepine, clentiazem (TA-3090), were investigated in rat cerebral cortex and skeletal muscle membranes with [3H]diltiazem and [3H]nitrendipine as radioligands. Clentiazem inhibited [3H]diltiazem binding to cerebral cortex membranes at the same concentrations as diltiazem at 2 degrees C. However, at 37 degrees C clentiazem was 3 times more potent to inhibit binding than diltiazem. [3H]Nitrendipine binding was modulated by clentiazem in a temperature-dependent manner. At 37 degrees C clentiazem significantly enhanced [3H]nitrendipine binding to rat cerebral cortex membranes, whereas it has an inhibitory effect on [3H]nitrendipine binding at 0 degree C and no effect at 25 degrees C. Of two optical isomers of clentiazem and four of diltiazem, only d-cis isomers (clentiazem and diltiazem) increased [3H]nitrendipine binding, indicating that both compounds have the same stereoselectivity for increasing [3H]nitrendipine binding. These results suggest that clentiazem binds to the same 1,5-benzothiazepine binding sites as diltiazem but with greater affinity.

Animals↗
PubMed1991

Substance P-evoked release of GABA from isolated spinal cord of the newborn rat.

Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the effects of substance P and its analogs on the release of endogenous GABA were examined. Application of substance P evoked a dose-dependent release of GABA from spinal cords. The threshold concentration of substance P for induction of a significant increase in the GABA release was 3 microM. The substance P-evoked GABA release was neither blocked by removal of Ca2+ from perfusion medium nor by tetrodotoxin. In contrast, the GABA release evoked by high K+ (90 mM) was abolished in Ca(2+)-free medium, and the GABA release evoked by veratridine (5 microM) was suppressed by tetrodotoxin (1 microM). A GABA uptake inhibitor, cis-4-hydroxynipecotic acid, markedly augmented the GABA release induced by high K+, but not that induced by substance P or veratridine. These results suggest the possibility that a carrier-mediated mechanism might be involved in the GABA release induced by substance P, as well as by veratridine, in the newborn rat spinal cord. Two N-terminal fragments of substance P, substance P free acid and substance P1-10 amide, as well as [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), evoked an increase in the GABA release, whereas substance P1-6, and a C-terminal fragment, substance P5-11 were inactive. Somatostatin and compound 48/80 also evoked a GABA release, which was independent of external Ca2+ and resistant to tetrodotoxin. [D-Pro4,D-Trp7,9,10]substance P4-11 (10-15 microM) inhibited the GABA release evoked by substance P, somatostatin and compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Substance P-evoked release of acetylcholine from isolated spinal cord of the newborn rat.

Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the release of endogenous acetylcholine was measured using high-performance liquid chromatography with an electrochemical detection system. Application of high-K+ (90 mM) medium evoked about an eight-fold increase in the acetylcholine release, and the K(+)-evoked release was Ca2+ dependent. Veratridine (20 microM) also evoked about a four-fold increase in the acetylcholine release, and this increase was suppressed by 0.2 microM tetrodotoxin. Application of substance P at 0.3-3 microM evoked a concentration-dependent release of acetylcholine. The substance P-evoked acetylcholine release was Ca2+ dependent and abolished by tetrodotoxin. Neurokinin A, neurokinin B, acetyl-Arg6-septide and senktide (3 microM each) also evoked a release of acetylcholine. Electrophysiological experiments using isolated spinal cords of newborn rats showed that bath application of substance P induced a depolarization of motoneurons, which was enhanced by edrophonium. This enhancement of substance P-induced depolarization by edrophonium disappeared in a low-Ca2+ medium or in the presence of atropine and dihydro-beta-erythroidine. In the presence of edrophonium and dihydro-beta-erythroidine, substance P induced an inhibition of monosynaptic reflex, and this inhibition was abolished by atropine. These results suggest that substance P and other tachykinins induce a release of acetylcholine from the newborn rat spinal cord by exciting cholinergic neurons.

Acetylcholine↗
PubMed1991

Three cases of respiratory dyskinesia.

We present here three cases of respiratory dyskinesia (RD). RD was observed with a video recording and other recordings were made of a respiratory airflow with a thermistor, and abdominal movement with a strain gauge. Neurological findings and CT scanning indicated marked organic changes in the brain in these 3 cases. RD was complicated with tardive dyskinesia of the tongue and lips, and the symptoms were aggravated during stress and absent during sleeping, which are the characteristic features of extrapyramidal symptoms. The symptoms of the three cases have improved by decreasing the dose of butyrophenone derivatives and discontinuing anti-parkinsonian drugs, which suggested that an intracerebral imbalance of DA and ACh may be the cause of RD.

Acetylcholine↗
PubMed1991

Effects of temperature and pressure during compression on polymorphic transformation and crushing strength of chlorpropamide tablets.

The effects of temperature on the polymorphic transformation of chlorpropamide during compression and on the physical properties of the tablet have been investigated. A heater and liquid nitrogen pool were mounted on the die of a single punch eccentric tableting machine, and the die temperature was controlled by a thermocontroller. A tableting machine with two load cells (upper and lower punches) and a non-contact displacement transducer were used to measure compression stress, distance and energy. The X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The amount of form C transformed from form A at 45 degrees C was about twice that at 0 degree C with the same compression energy. The amount of form A transformed from form C by compression at 45 degrees C was almost the same as that at 0 degree C. This suggests that the mechanochemical effect of form A depended on the compression temperature, but that of form C was independent of temperature. The crushing strength of tablets of form A was about twice that of form C, even at the same porosity. The plots of log (crushing strength of tablet) against porosity of form A tablets compressed at 0 and 45 degrees C were linear with the same slope; the slope for form C tablets compressed at 45 degrees C was less than that at 0 degree C.

Chemistry, Pharmaceutical↗
PubMed1991

Isomerization of lactose in solid-state by mechanical stress during grinding.

Isomerization during grinding of solid-state alpha-monohydrate, alpha-anhydrate and beta-anhydrate of lactose was investigated. Samples were ground in an agate centrifugal ball-mill at 270 rev min-1 at room temperature (20 degrees C). The crystallinity of ground lactose was measured by Hermans' method from the powder X-ray diffraction profiles. The alpha- and beta-lactose content of the ground lactose was obtained from the specific rotation measured by using angular rotation spectrophotometry. The crystalline lactose samples were transformed into non-crystalline solids by mechanical stress during grinding. After grinding, the water content of all ground lactose samples increased, and the samples had about 2 mol water per lactose after 10 h grinding. After 10 h grinding of alpha-monohydrate and alpha-anhydrate, 10 and 15%, respectively, of alpha-lactose was transformed into beta-lactose by the mechanical treatment. After 10 h grinding of beta-lactose, 20% of beta-lactose was transformed into alpha-lactose. The results suggest that crystalline lactose was transformed into a non-crystalline solid, and water was adsorbed on the non-crystalline lactose. The non-crystalline solids of alpha- or beta-lactose were then transformed into their counterparts by the mechanochemical effects of grinding.

Chemical Phenomena↗
PubMed1991

Effects of tableting pressure on hydration kinetics of theophylline anhydrate tablets.

The effects of tableting pressure on hydration kinetics of types I and II theophylline anhydrate tablets at 95% relative humidity, 35 degrees C, have been studied by using various kinetic equations. Relations between tablet expansion and hydration were studied. Samples of 2 cm diameter tablets (1 g) were compressed at 5, 10 and 20 MPa. The hydration of types I and II tablets decreased with increased tableting pressure. The time required for 50% hydration of 2 cm diameter tablets, compressed at various pressures suggests that the tablet hydration rate was affected by the tableting pressure. Types I and II tablets expanded 11.37-16.75% in volume during hydration to the monohydrate. The thickness expansion of the tablets exceeded the diameter expansion as the tablet structure was not uniform owing to the orientation of particles during the compression. The final expansion ratio of the tablets increased with increased tableting compression pressure. The Hancock Sharp constant (m) and fitting of the kinetic data to a suitable model suggested that the hydration of theophylline anhydrate tablets followed the two-dimensional phase boundary equation (type I tablets) or the three-dimensional phase boundary equation (type II tablets).

Chemical Phenomena↗
PubMed1991

Striatal blood flow, glucose metabolism and 18F-dopa uptake: difference in Parkinson's disease and atypical parkinsonism.

Striatal blood flow, glucose metabolism and 18F-Dopa uptake were studied with positron emission tomography (PET) in eight non-demented patients with idiopathic Parkinson's disease and eight with atypical Parkinsonism. Patients with atypical Parkinsonism had no specific cause for the Parkinsonian symptoms and were clinically different from Parkinson's disease with lack of resting tremor and a poor response to dopaminergic drugs. Decreased 18F-Dopa uptake in the putamen was observed in patients with Parkinson's disease and atypical Parkinsonism compared with normal controls. 18F-Dopa uptake in the head of the caudate was also significantly reduced in both conditions but relatively less in Parkinson's disease. Decreased blood flow and glucose metabolism in the striatum associated with a global cerebral decrease were also observed in patients with atypical Parkinsonism compared with controls, while they were preserved in patients with Parkinson's disease, indicating affected neurons not only in the striatum but also in the cerebrum in patients with atypical Parkinsonism compared with patients with Parkinson's disease. The differences in the caudate 18F-Dopa uptake, and blood flow and glucose metabolism in the cerebrum including the striatum between Parkinson's disease and atypical Parkinsonism assessed by PET may be due to the differences in the pathophysiological mechanism between Parkinson's disease and atypical Parkinsonism.

Adolescent↗
PubMed1991

The regulatory effect of ascorbate on the carnitine synthesis in primary cultured guinea pig hepatocytes.

The effect of ascorbate (AsA) on the synthesis of carnitine from gamma-butyrobetaine (BB) in primary cultured guinea pig hepatocytes was investigated. The hepatocyte monolayers preloaded with AsA were incubated for 4 h in medium with various concentrations of BB as the precursor of carnitine. The accumulation of carnitine reached a maximum when the cells were incubated with 0.05-1.0 mM BB and significantly decreased with excess BB (5 mM). In contrast, increasing concentrations of AsA supplemented to medium led to an increase in carnitine content, but AsA and total AsA contents in cells decreased by BB supplementation. Regarding the enhancement of hydroxylation of BB in the hepatocytes, AsA was the most effective among such other reducing agents as glutathione and dithiothreitol. Although erythorbate (ErA) also stimulated the hydroxylation of BB, carnitine content in cells preloaded with ErA was only 60% of that with AsA. These results suggest that AsA is specifically required for the hydroxylation of BB. Furthermore, AsA can regulate carnitine synthesis in the primary cultured guinea pig hepatocytes.

Animals↗
PubMed1991

Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography.

In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects.

Adult↗