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Biomedical subjects

I Inoue

Publications and source records attributed to I Inoue.

At least 217 records · Page 12Linked to original sources
PubMed1987

[A randomized controlled trial of acute and delayed cisplatin-induced emesis with metoclopramide, dexamethasone and prochlorperazine].

Forty patients with advanced lung cancer who had received chemotherapy containing cisplatin (80 mg/m2) were accrued for a randomized controlled trial to evaluate the additional effect of prochlorperazine on the combination of high-dose metoclopramide and dexamethasone for the treatment of acute cisplatin-induced emesis. The effect of intravenous metoclopramide and dexamethasone in emesis occurring more than 24 hours after cisplatin administration was also evaluated. Excellent emetic control (no emesis during 24 hours after cisplatin administration) was achieved in 70% (14/20) and 76% (16/21) of the patients who received the combination of prochlorperazine, metoclopramide and dexamethasone and the combination of metoclopramide and dexamethasone, respectively. The overall toxicities associated with both regimens were not serious and were similar. Patients treated with metoclopramide and dexamethasone on days 2-7 experienced less delayed emesis, nausea and anorexia compared with those treated with a placebo (delayed emesis, 25% versus 50%, respectively, p = 0.105; more than 4 days of nausea, 10% versus 35%, respectively, p = 0.059; less than 3 days of anorexia, 80% versus 50%, respectively, p = 0.048). It was concluded that metoclopramide and dexamethasone showed an excellent antiemetic effect on acute drug-induced emesis, as well as on delayed emesis, induced by cisplatin.

Adult↗
PubMed1987

[Basic studies on chemotherapy of brain tumors by means of liposomes: affinity of sulfatide-inserted liposomes to human glioma cells].

In order to utilize liposomes for the treatment of brain tumors, we examined the interaction between the cells and the liposomes prepared from phosphatidylcholine, cholesterol, and sulfatide (molar ratio, 7:2:1), which were able to deliver the encapsulated materials into the brain through the blood-brain barrier. With a variety of human cell lines, the incorporation of the liposomes and the release of the liposomal contents into cells were studied by spectrofluorometry and flow cytometry by use of encapsulated 6-carboxy-fluorescein. It was found that the amounts of liposomes incorporated into cells were dependent on the dose of liposomes and type of cells. At the same concentration of liposomes, the highest incorporation was found for glioma cells, which was further confirmed by electron microscopy with ferritin-containing liposomes. These results indicate that the liposomes composed of sulfatide, phosphatidylcholine and cholesterol have a high affinity for human glioma cells and should be useful for the chemotherapy of glioma when antitumor drugs are encapsulated into them.

Antineoplastic Agents↗
PubMed1986

Modification of K conductance of the squid axon membrane by SITS.

The effects of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) on the K conductance, gK, were studied in internally perfused giant axons from squid, Doryteuthis. SITS at 3-200 microM was applied intracellularly by adding the reagent to the internal perfusion fluid. Three remarkable changes in gK were noted: there was a slowing of the opening and closing rates of the K channel in the whole voltage region; K channels modified with SITS started to open at voltages below -100 mV, and thus 30% of total K channels were open at the level of normal resting potential (approximately -60 mV) after the maximal drug effect was attained (less than 30 microM); there was a disappearance of gK inactivation that became distinct at relatively high temperature (greater than 8 degrees C). These drug effects depended solely on the drug concentration, not on factors such as repetitive alterations of the membrane potential, and the changes in gK were almost irreversible. Another disulfonic stilbene derivative, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), had similar effects on gK, but the effects were approximately 1.5 times stronger. These changes in gK were somewhat similar to alterations in gNa produced by an application of veratridine, batrachotoxin, and grayanotoxin, which are known as Na channel openers.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1986

[A phase II study of UFT in non-small cell lung cancer].

A phase II evaluation of UFT, a mixture of tegafur and uracil, was performed in 13 patients with non-small cell lung cancer (eight patients with adenocarcinoma and five patients with squamous cell carcinoma). UFT at a dose of 600 mg was given per os every day for more than four weeks. Among 12 evaluable patients, one patient with adenocarcinoma of the lung showed partial response. The response rate for UFT was 8.3%. Toxic effects included anorexia (31%), nausea (15%), liver disorder (15%), and pigmentation (8%).

Adenocarcinoma↗
PubMed1986

Messenger RNA coding for argininosuccinate synthetase in citrullinemia.

Messenger RNA coding for argininosuccinate synthetase (ASS), extracted from the livers of some patients with citrullinemia, was analyzed using a cell-free translation system and dot and Northern blot hybridization with cDNA probe for ASS. In patients with quantitative-type citrullinemia, called type II here, previous studies have demonstrated that the hepatic content of the enzyme was about 10% of the control value, whereas the translatable mRNA level for the enzyme was similar to that of control livers. Here, we confirmed that the type II liver contained an almost normal amount of mRNA coding for ASS, judged by the dot-blot hybridization technique with cDNA. Northern blot hybridization of RNA indicated that there was hybridizable mRNA of approximately normal size (about 1.7 kilobase [kb]) in each, suggesting that large structural gene deletions had not occurred. These results indicate that in type II citrullinemia, the decrease in the enzyme protein is due either to increased degradation of the enzyme or to decreased or inhibited translation in the liver. Another type of citrullinemia was found and classified as type III. It is characterized by no detectable enzyme activity for ASS or translation activity for ASS mRNA. However, a smaller amount of RNA molecule hybridized for ASS cDNA was detected.

Adult↗
PubMed1985

Specific binding sites for atrial natriuretic peptide (ANP) in cultured mesenchymal nonmyocardial cells from rat heart.

Specific binding sites for atrial natriuretic peptide (ANP) were studied in cultured mesenchymal nonmyocardial cells (NMC) from rat heart. Binding study using 125I-labeled synthetic rat (r) ANP revealed the presence of a single class of high-affinity binding sites for rANP in cultured NMCs derived from both atria and ventricles; the apparent dissociation constant (Kd) was approximately 0.2 - 0.3 nM and the number of maximal binding sites was approximately 190,000 - 300,000 sites/cell. rANP significantly stimulated intracellular cGMP formation of cardiac NMCs in a dose-dependent manner (1.6 X 10(-8) M - 3.2 X 10(-7) M). rANP had no effect on synthesis of prostaglandin I2 by cultured cardiac NMCs. The physiological significance of ANP action on cardiac tissue remains to be determined.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Voltage-dependent chloride conductance of the squid axon membrane and its blockade by some disulfonic stilbene derivatives.

When giant axons of squid, Sepioteuthis, were bathed in a 100 mM Ca-salt solution containing tetrodotoxin (TTX) and internally perfused with a solution of 100 mM tetraethylammonium-salt (TEA-salt) or tetramethylammonium-salt (TMA-salt), the membrane potential was found to become sensitive to anions, especially Cl-. Membrane currents recorded from those axons showed practically no time-dependent properties, but they had a strong voltage-dependent characteristic, i.e., outward rectification. Cl- had a strong effect upon the voltage-dependent membrane currents. The nonlinear property of the currents was almost completely suppressed by some disulfonic stilbene derivatives applied intracellularly, such as 4-acetoamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which are blockers of chloride transport. On the basis of these experimental results, it is concluded that a voltage-dependent chloride-permeable channel exists in the squid axon membrane. The chloride permeability (PCl) is a function of voltage, and its value at the resting membrane (Em = -60 mV) is calculated, using the Goldman-Hodgkin-Katz equation, to be 3.0 X 10(-7) cm/s.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1985

[Combination therapy with HU IFN-beta and ACNU against malignant brain tumors, Part 1. Experimental study in vitro].

Augmentation of cytotoxicity against malignant glioma using a combination of Hu IFN-beta and ACNU was analyzed in vitro from the points of cell growth inhibition and alteration of the DNA histogram. Cytotoxicity was tested by exposing 13 human glioma cell lines to ACNU at a concentration of 5 micrograms/ml and/or Hu IFN-beta at a concentration of 10(3) IU/microliters. These concentrations were considered to be clinical doses. Additive or synergistic effects of the combination of the two agents were observed in all cell lines tested. The cytotoxic effect of two log kill was seen in two cell lines given ACNU treatment alone, one cell line treated with Hu IFN-beta alone, and nine treated with the combination. Flow-cytometry studies of the DNA histogram showed accumulation in the G2+M phase with ACNU and in the S phase with Hu IFN-beta. On the other hand, marked accumulation using the combination in the S phase followed by the G2+M phase was observed and this accumulation lasted for over a week. The present results show an augmentation of antitumor activity and suggest the effectiveness of combined Hu IFN-beta/ACNU therapy in the treatment of patients with malignant glioma.

Antineoplastic Agents↗
PubMed1985

[Analysis of various factors related to the prognosis of medulloblastoma].

Thirty-three patients with medulloblastoma were treated in our department by surgical resection of tumor and radio-chemotherapy, and obtained 40.1% of 5 year survival. The present study analyzed the various factors related to the prognosis from clinical and pathological points of view in our series. Good factors were extensive resection of tumor and completement of whole CNS radiationtherapy. In contrast, poor factors were the presence of subarachnoid dissemination of tumor and identification of differentiated cells in tumor tissue histologically. The protection and treatment of subarachnoid dissemination was difficult with any kind of therapy. With surgical specimens obtained from 26 patients, glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) were stained immunohistochemically. Two cases out of 12 with GFAP and/or NSE positive cells are alive and their mean survival time is 27 months. On the other hand, eight cases out of 14 without GFAP nor NSE positive cells are alive and their mean survival time is 44 months.

Adolescent↗
PubMed1985

Synthesis of 5'(3')-O-amino nucleosides.

Synthetic methods leading to 5'(3')-O-amino nucleosides have been developed in an effort to prepare derivatives that may have antitumor or antiviral activities. They are based on ring opening of O2,5'-cyclonucleosides with the N-protected hydroxylamines and dehydrative coupling of 5'(3')-O-unprotected nucleosides with N-hydroxyphthalimide.

Amino Sugars↗
PubMed1984

Stage Ib, IIa, and IIb cervix cancer, postsurgical staging, and prognosis.

Two hundred fifty-five cases of International Federation of Gynecology and Obstetrics (FIGO) Stage Ib, IIa, and IIb cases of cervical cancer were analyzed following radical surgery with regard to the extent of invasion into vagina, parametria, and pelvic lymph nodes. Restaging was carried out based on the findings. Discrepancies were found between FIGO stages and the actual extent of the disease, particularly in Stage IIb. Among 99 cases of Stage IIb, only 42.4% were correctly staged. The 5-year disease-free survival by FIGO and postsurgical stagings were, respectively: Ib, 88.4% and 87.0%; IIa, 85.2% and 95.0%; IIb, 70.7% and 62.3%. Prognostic significance in the pathologic examination of operated materials was demonstrated when there were deep stromal invasions of cancer cell or parametrial invasions or pelvic lymph node metastases. When cancer was present in both of the parametrium and pelvic lymph nodes, the prognosis of the patient worsened (5-year survival rate, 41.4%).

Adenocarcinoma↗
PubMed1984

Pressure dependence of sodium gating currents in the squid giant axon.

Asymmetric displacement currents, Ig, were measured in squid axons at different hydrostatic pressures, P, up to 60 MPa. Potassium and sodium currents were abolished by intracellular Cs+ and TEA+, by extracellular Tetrodotoxin (TTX), and by Na+ substitution with Tris+. The time course of Ig became progressively slower with increasing pressure, and the amplitude decreased. With appropriate scaling in time and amplitude, Ig records at any given P could be made to superimpose very well with those obtained at atmospheric pressure. The same scaling factors yielded a good superposition of all records obtained for voltage steps to membrane potentials in the range -30 to +42 mV. The ratio between the amplitude and time factors was larger than unity and increased with P, indicating a progressive decrease (up to 35% at 60 MPa) of the total charge displaced, Q, with no significant change in its voltage dependence. The time-scaling factor increased exponentially with P, as expected if all the steps involved in the opening of a sodium channel, and producing a major charge redistribution, have the same activation volume, delta V not equal to g approximately 17 cm3/mol. This value is roughly one-half of that characterizing the pressure dependence of sodium current activation, suggesting that some late, rate-limiting step in the opening of sodium channels has a large activation volume without being accompanied by an easily detected charge movement. Part of the decrease of Q with pressure could be attributed to an increase in sodium inactivation. However, we cannot exclude the possibility that there is a reversible reduction in the number of fast activating sodium channels, similar to the phenomenon that has been reported to occur at low temperatures (Matteson and Armstrong 1982).

Animals↗