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Biomedical subjects

H Shimura

Publications and source records attributed to H Shimura.

At least 145 records · Page 8Linked to original sources
PubMed1989

Distributions of tegafur in tissues of gastric adenocarcinoma patients: tissue uptakes and concentrations in plasma after oral and rectal administrations.

Fifty-one gastric adenocarcinoma patients were divided into two groups, according to the route of administration of the anticancer drug. One group was given FT-207 (tegafur, an enteric coated granule) orally and the other group, FT-207 in the form of a suppository. Blood and tissue concentrations of the drug were examined after a three-day administration of 750 mg at 09.00 and 21.00 hours. There were no significant differences between the two groups with respect to the concentrations of FT-207 and its metabolite 5-FU in the tissues. Levels of 5-FU in the excised tumor averaged 0.256 and 0.160 micrograms/g, in oral and rectal administrations, respectively, and levels in normal lymph nodes averaged 0.174 and 0.179 micrograms/g, respectively. The difference in 5-FU levels between normal and tumor tissues was statistically significant (P less than 0.05).

Adenocarcinoma↗
PubMed1988

Active production and membrane anchoring of carcinoembryonic antigen observed in normal colon mucosa.

Normal colon mucosa was found to produce carcinoembryonic antigen (CEA) quite actively as cancerous tissues do when maintained in an organ culture, although the fresh normal mucosae contained a very small quantity of CEA unlike cancerous tissues. This is consistent with an active expression of CEA mRNA in normal mucosa comparable to that in cancerous tissues actively producing CEA, and suggests that the normal cell product was rapidly released into the lumen of digestive tract and turned into normal fecal antigens (NFAs) previously found in feces. 3H-Labeled precursors of glycophospholipid such as ethanolamine and stearic acid were incorporated into CEA produced by both normal and cancerous tissues, suggesting that CEA in normal mucosa is anchored to the cell membrane through a glycophospholipid as in cancerous tissues.

Blotting, Northern↗
PubMed1988

Selective cytotoxicity of phospholipids and diacylglycerols to rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene.

The colony-forming ability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was drastically reduced when the cells were cultivated for 18 h in medium augmented with 300 micrograms/ml of liposomes composed of either phosphatidylcholine (PC) or phosphatidylinositol. In contrast, those of untransformed 3Y1 cells and simian virus 40-transformed and polyomavirus-transformed 3Y1 cells were not. The cytotoxicity of PC liposomes was also observed in 3Y1 cells transformed by plasmid DNA containing Ad12-E1A gene but not in those transformed by adenovirus type 2, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene. The extensive killing of Ad12-transformed and E1A-transformed 3Y1 cells occurred in liposomes of dioleoyl-PC and of dilinoleoyl PC but not those of dipalmitoyl PC, distearoyl-PC, or diarachidonyl PC, suggesting that the acyl groups of phospholipids play an important role in cytotoxicity. Dilinoleoylglycerol, 60 micrograms/ml, was also cytotoxic selectively to Ad12-transformed and E1A-transformed 3Y1 cells, although the toxicity of lysophosphatidylcholine or linoleic acid was not specific to these transformants. These results suggest that cell transformation by Ad12 is characterized by a high sensitivity to exogenously administered phospholipids and diacylglycerol that contain oleoyl or linoleoyl acyl groups and that the sensitivity is attributable to the expression of E1A gene of Ad12.

Adenovirus Early Proteins↗
PubMed1988

A possible mechanism on the potentiating vascular effect of coadministration of ifenprodil tartrate and calcium hopantenate: a study in the internal carotid artery.

Recently, it has been proposed that the combined administration of ifenprodil tartrate and calcium hopantenate might produce a beneficial synergistic effect in the treatment of cerebrovascular diseases. To further examine this clinical phenomena, the blood flow in the internal carotid arteries of the rat and the isometric tension of canine internal carotid arteries were measured with a transit-time ultrasonic volume flowmeter and a force transducer, respectively. Ifenprodil tartrate produced a sustained increase in the internal carotid arterial blood flow of rats, while calcium hopantenate had no effect. However, the increase in the internal carotid arterial blood flow induced by ifenprodil tartrate was significantly enhanced by calcium hopantenate. Ifenprodil tartrate caused a dose-related relaxation of K+-induced contractions in the isolated canine internal carotid arteries, while calcium hopantenate had no effect. The dose-response curve of ifenprodil tartrate was shifted to the left by pre-incubation in calcium hopantenate. Ifenprodil tartrate inhibited the K+-induced Ca2+ uptake in the canine internal carotid arteries, and the inhibition induced by ifenprodil tartrate was significantly enhanced by calcium hopantenate. These results suggest that the observed enhancement by calcium hopantenate of the ifenprodil tartrate effect on the internal carotid arterial blood flow was due to increased vascular myorelaxation resulting from the influence of calcium hopantenate on the Ca2+ movement.

Animals↗
PubMed1988

A possible mechanism on the potentiated vascular effect of coadministration of ifenprodil tartrate and calcium hopantenate: a study in the basilar and vertebral arteries.

In our earlier report [Shibuya et al. in press], we demonstrated the partial mechanism of the synergism between ifenprodil tartrate and calcium hopantenate on cardiovascular diseases. The mechanisms of the synergistic effects in the basilar and vertebral arteries were further studied in this paper using our described methods. Ifenprodil tartrate produced a sustained increase in the vertebral arterial blood flow of rats, while calcium hopantenate. Ifenprodil tartrate caused dose-related relaxation of K+-induced contractions in by ifenprodil tartrate was significantly enhanced by the coadministration of calcium hopantenate. Ifenprodil tartrate caused dose-related relaxation of K+-induced contractions in isolated canine basilar arteries, while calcium hopantenate had no effect. The dose-relaxation curve of ifenprodil tartrate was shifted to the left by pre-incubation in calcium hopantenate. In K+-depolarized basilar arteries, ifenprodil competitively antagonized the response to Ca2+, and this was enhanced by pre-incubation in calcium hopantenate. Ifenprodil tartrate inhibited K+-induced Ca2+ uptake in canine cerebral arteries and this was enhanced by pre-incubation in calcium hopantenate. These results suggest that the enhancement by calcium hopantenate of the ifenprodil tartrate effect on the vertebral blood flow is due to increased vascular relaxation through the inhibition of Ca2+ influx.

Animals↗
PubMed1988

Effects of ifenprodil tartrate on vertebral, basilar and internal carotid arteries.

Changes in blood flow of vertebral and internal carotid arteries of rats after the administration of ifenprodil tartrate were measured using the transit-time ultrasonic volume flowmeter. Tension of isolated canine basilar and internal carotid arteries was also tested isometrically. Ifenprodil tartrate produced a sustained increase in both vertebral and internal carotid arterial blood flow of rat. The increase in blood flow was greater in vertebral than in internal carotid arteries. Papaverine hydrochloride transiently increased arterial blood flow in both the vertebral and internal carotid arteries to approximately the same extent. Ifenprodil tartrate induced dose-related relaxation in basilar and in internal carotid arteries contracted with K+ (50 mM), and its effects were greater in basilar than in internal carotid arteries, while relaxation induced by papaverine hydrochloride was about the same in both arteries. These results suggest that the significant increase of vertebral arterial blood flow induced by ifenprodil tartrate is due to the peculiarity of vascular myorelaxation by this drug.

Animals↗
PubMed1987

Effects of inhibitors of the cytoplasmic structures and functions on the early phase of infection of cultured cells with simian virus 40.

To obtain information about cytoplasmic structures and functions involving the entry of simian virus 40 virions into cells, we examined whether the inhibitors that affect the functions and/or structure of lysosomes, cell membrane, and cytoskeletons inhibit expression of nuclear T antigen in the SV40-inoculated rat 3Y1 and monkey CV-1 cells. Chloroquine, methylamine, and butylamine did not inhibit T-antigen expression, suggesting that lysosomal acidification is not required for establishment of infection. Cytochalasin B had no effect, suggesting that microfilaments are not involved. Monensin, colcemid, and amantadine each inhibited T-antigen expression at doses causing no obvious cytotoxicity. Maximal inhibition was seen when these inhibitors were added to the cultures within 1 hr (monensin), within 4 hr (colcemid), or within 12 hr (amantadine) after virion adsorption to the cell surface. When the inhibitor was present in the virus-inoculated cultures for 24 hr and then removed, nuclear T antigen began to be expressed at 4 hr (monensin), 9 hr (colcemid), or 1 hr (amantadine) after removal of the inhibitors. Results of SDS-PAGE analysis of immunoprecipitated radiolabeled proteins of infected cells revealed that amantadine inhibited synthesis of large and small T antigens as well as general protein synthesis. Inhibition by colcemid may be due to disruption of microtubules, because other microtubule-disrupting agents (colchicine, vinblastine, nocodazole, and podophyllotoxin) also inhibited appearance of nuclear T antigen but lumicolchicine and taxol did not. Electron microscopy revealed that, in the presence of colcemid, although the adsorbed virions were readily internalized to form pinosomes, vectorial movement of the pinosomes to the nucleus appeared to be inhibited. Results of electron microscopy also suggest that inhibition by monensin may occur mainly in internalization of adsorbed virions and that the inhibition is leaky such that the early steps of infection proceed slowly in the presence of monensin. We conclude that monensin, colcemid, and amantadine interfere with mutually different early events of SV40 infection.

Amantadine↗
PubMed1987

Positional nystagmus of benign paroxysmal type (BPPN) due to cerebellar vermis lesions. Pseudo-BPPN.

Positioning nystagmus accompanied by severe vertigo had been reported in patients with partial lesions of the inner ear, especially otolith lesions. Typically this type of nystagmus represents a latent period and subsequent fatiguability. We concur with this finding and have constantly emphasized the significance of this phenomenon in clinical diagnosis. Since we started to use CT-scanning, this type of nystagmus has been noted in 20 patients, all of whom had cerebellar vermis lesions. Attention should be focused on this association. A simple coincidence could not be excluded if such a combination were seen in only 1 or 2 patients, it could be attributed to simple coincidence. But its occurrence in as many as 20 patients a causal role of cerebellar vermis lesions. Its mechanism may be explained by incomplete inhibition of the vestibulo-oculomotor system including the cerebellar flocculonodular lobe or vestiburo-cerebellum.

Arachnoid↗
PubMed1986

Activation of purified simian virus 40 virions by free amino-group containing phospholipid liposomes.

The infectivity of the simian virus 40 (SV40) virions purified after treatment with sodium deoxycholate is activated by mixing, prior to infection, the virions with the liposomes composed of phosphatidylserine or a mixture of phosphatidylethanolamine and phosphatidylcholine (H. Shimura, and G. Kimura (1985), Virology 144, 268-272). The sucrose-CsCl cushion sedimentation analysis of the virions mixed with the liposomes revealed that the density of the radiolabeled virions became lower and that of the radiolabeled liposomes became higher to give a similar range, suggesting the binding of virions with the liposomes. Electron microscopy revealed the side-to-side association of virions with liposomes. The efficiency of adsorption of the virions to monkey kidney BSC-1 cells varied depending on phospholipid types mixed with virions and did not always become high. In the case of phosphatidylethanolamine liposomes, the free amino group in the phospholipid molecule was essential for the activation of the virion infectivity, because mono- and di-methylated phosphatidylethanolamine failed to activate the infectivity. Fluid nature of phospholipids seemed to be necessary also for the infectivity activation, because dipalmitoyl and distearoyl phospholipids did not activate virion infectivity at 37 degrees, the temperature at which the liposomes of these phospholipids are supposed to be in a solid state. Presence of free amino groups and difference in acyl groups of the phospholipids did not influence the adsorption of the virions to cells. These results suggest that events which occur after adsorption of virions to cells are responsible for the activation of the SV40 virion infectivity by the liposomes composed of free amino-group containing phospholipids.

Adsorption↗
PubMed1986

Accumulation of cells with 4N DNA content at nonpermissive temperature in rat embryo diploid cells transformed by tsA mutant of simian virus 40.

Primary rat embryo cells were transformed by a tsA mutant (tsA640) of simian virus 40 (SV40). Proliferation of all four independent diploid transformants was suppressed at a nonpermissive temperature (40.3 degrees C), being accompanied by a marked increase in the fraction of cells with a 4N DNA content (a 4N peak in the flow cytofluorogram). However, in this case, the fraction of cells with a 2N DNA content (a 2N peak in the flow cytofluorogram) was preserved. Both effects (suppression of proliferation and increase in the 4N peak) diminished when transformed cells were superinfected with wild-type SV40. The increased 4N peak was preserved, albeit not completely, for at least 24 hours, when cells were further incubated in the presence of hydroxyurea at the nonpermissive temperature. On the other hand, the preserved 2N peak all but disappeared within 24 hours, when cells were further incubated in the presence of colcemid at the nonpermissive temperature. These results suggest that the thermolabile large T antigen of SV40 directly or indirectly induces an accumulation of cells with a 4N DNA content, at the nonpermissive temperature, by prolonging the G2 (and/or late S) period.

Animals↗
PubMed1986

[5-FU concentration in the blood and tissue of patients with gastric and colorectal cancer after administration of UFT or tegafur].

UFT or tegafur (5, 7.5 and 15 mg/kg, respectively) were given to Donryu rats with AH-130 cancer twice a day for 3 days, and 5-FU concentrations in the blood, tumor, normal stomach and large bowel tissues were measured by chemical assay and compared. The 5-FU concentrations in the tumor were higher than those of normal tissues and still remained 12 hours after the final dosage. According to increased UFT dosage, there were significantly higher levels of 5-FU concentration in tumor tissues but blood levels of 5-FU were low. The peak of concentration occurred at one to two hours after the final dosage. However, increase in tegafur dosage volume did not correlate with 5-FU levels. Clinical cases (74 patients) of gastric and colorectal cancer were orally administered UFT or tegafur at 300 mg twice a day for 3 days preoperatively. Materials were obtained at surgery at 5.5 hours on average after the final dosage and 5-FU levels in tissues were measured by chemical assay. Concentrations of 5-FU in cancerous tissues after UFT administration were 0.177 +/- 0.131 micrograms/g in gastric cancer and 0.130 +/- 0.051 micrograms/g in colorectal cancer, while in patients to whom tegafur had been administered, the concentrations were 0.194 +/- 0.124 micrograms/g and 0.119 +/- 0.075 micrograms/g, respectively. There was no significant difference in 5-FU levels between the UFT-administered group and the tegafur group.

Animals↗
PubMed1985

Phospholipid liposomes enhance the infectivity of purified simian virus 40 virions.

When simian virus 40 virions purified after treatment with sodium deoxycholate were incubated with the extract of monkey kidney CV-1 cells, infectivity of the virions was enhanced. The infectivity-enhancing activity was recovered from the phospholipid fraction of CV-1 cells. The constructed liposomes composed of phosphatidylserine were able to enhance the infectivity of the purified virions, but those composed either of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, or phosphatidylinositol could not. The liposomes constructed with a mixture of phosphatidylethanolamine and phosphatidylcholine at a ratio of 1:1 (w:w) also enhanced the infectivity of the purified virions. Pretreatment of cells with liposomes either of phosphatidylserine or of phosphatidylethanolamine did not enhance susceptibility of the cells to infection with the purified virions. These observations suggest that the major phospholipids of the cellular membrane, when associated with virions, play a vital role in activation of purified virions.

Animals↗
PubMed1985

Cell growth and differentiation in vitro in mouse macrophages transformed by a tsA mutant of simian virus 40. III. Large T antigen level and cell proliferation and survival in an SV40 tsA640-transformed macrophage line.

The levels of simian virus 40 (SV40) large T antigen in a tsA-transformed mouse macrophage line at the permissive (33 degrees C) and the nonpermissive (39 degrees C) temperature were examined by immunofluorescence, sodium dodecylsulfate-polyacrylamide gel electrophoresis, complement fixation, and enzyme-linked immunosorbent assay. When the cells were confluent and rested at 33 degrees C, and then were shifted to 39 degrees C, the amount of large T antigen per cell decreased, and most cells survived and remained phagocytic. When the cells were proliferating at 33 degrees C, and then were shifted to 39 degrees C, the cells died with only a small reduction in the amount of large T antigen. Therefore, the physiological state of the cells may determine the survival of cells by affecting the level of large T antigen after exposure to 39 degrees. The confluent cells may be rested with a concomitant decrease of large T antigen. The proliferating cells may not survive in the presence of a relatively high level of functionally defective large T antigen at 39 degrees C.

Animals↗
PubMed1985

[A clinical study of cefotaxime in patients with infections complicating a disorder of the hemopoietic tissue. Its therapeutic effect and influence on the coagulation system].

Twenty infectious episodes were caused mainly by Gram-negative rods in 16 patients with a disorder of the hemopoietic tissue. The ages of the patients ranged between 20 and 76 years. Cefotaxime (CTX) was used alone in 9 infectious episodes (group I) and in combination with other antibiotics in the remaining 11 infectious episodes (group II). The following results were obtained. A good response to CTX was noted. The clinical and bacteriological success rates were 100% and 83% in group I, and 82% and 100% in group II, respectively. Bleeding was not clinically found during and after treatment of any infectious episodes with CTX. No change in PT and aPTT was noted during CTX treatment, either. CTX was thus evaluated to be an effective and safe cephem antibiotic in the treatment of infectious episodes secondary to a disorder of the hemopoietic tissue, which is usually accompanied by a marked hemorrhagic tendency.

Adult↗