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Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 199 records · Page 11Linked to original sources
PubMed2001

Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters.

To control the growth of primary tumors effectively with systemic chemotherapy, we recently developed intravenously administered small-sized magnetic liposomes as an anticancer drug carrier. We previously reported that intravenously administered magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) effectively delivered ADR to the target site where a permanent magnet was implanted. In the present study, the therapeutic efficacy of this novel treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, was further evaluated by comparing tumor growth rates among different administration modalities and by histological examination of treated tumors. Small-sized magnetic ADR liposomes with a mean diameter of 146 nm were prepared by the reverse-phase evaporation method. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. One day prior to the animal study, either a permanent magnet (with magnetic force) or non-magnetic alloy (without magnetic force) was implanted in the center of the tumors. Treatment with magnetic ADR liposomes under magnetic force showed significantly greater antitumor activity than intravenous administration of ADR solution or that of magnetic ADR liposomes without magnetic force. ADR administered as magnetic liposomes eliminated weight loss of hamsters, one of the side effects produced by ADR. Interestingly, magnetic liposomes (without incorporated ADR) given under magnetic force also suppressed the tumor growth. The selective accumulation of magnetite particles in the tumor blood vessels was observed by histological examination. These results suggest that this systemic chemotherapy can effectively control the primary tumor without significant side effects, due to the targeting of magnetic ADR liposomes.

Animals↗
PubMed2001

Effect of thermosensitive liposomal doxorubicin with hyperthermia on primary tumor and lung metastases in hamster osteosarcoma.

We evaluated the effect of intravenous thermosensitive liposomal doxorubicin (TL-DOX) together with local hyperthermia on primary tumors in highly metastatic hamster osteosarcoma. This combination resulted in higher DOX concentrations in plasma, primary tumors and lungs than standard DOX under the same conditions. Tumor growth and lung metastasis were also inhibited more by TL-DOX and hyperthermia than by hyperthermia alone, DOX with or without hyperthermia, and TL-DOX without hyperthermia. In addition, gains in hamster body weight were not suppressed. These results suggest that the combination of TL-DOX and hyperthermia can control primary tumors and suppress lung metastasis in hamsters.

Animals↗
PubMed2001

Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model.

PURPOSE: Because purinoceptor P2Y(2) receptor agonists elicit increases in net Cl, fluid transport, and glycoprotein release onto the ocular surface, they are candidates for treatment of dry eye syndrome. Accordingly, the effects of such an agonist INS365 on these parameters were characterized in a rat dry eye model. METHODS: An SD rat dry eye model was used in which exorbital lacrimal gland extirpation decreased the Schirmer test score by at least 50%. After 8 weeks, when significant increases occurred in corneal epithelial permeability, INS365-containing eye drops were applied six times daily for the next 4 weeks at concentrations from 0.03% to 3.0%. Corneal barrier function was evaluated based on measurements with a modified anterior fluorometer of fluorescein penetrance at 1, 2, and 4 weeks after initial application. After INS365 application, the periodic acid-Schiff reagent (PAS)-stained area was evaluated in histologic sections of the tarsal and bulbar conjunctiva. RESULTS: Ten minutes after INS365 eye drop application at doses of either 3. 0% or 8.5%, a 1.5-fold transient increase in tear fluid secretion occurred in both the control and dry eye model animals. These transient increases nearly returned to baseline after 60 minutes. Furthermore, after 5 minutes, 1.0% INS365 was sufficient to cause a maximal transient decrease in the PAS-stained area of more than 30%, which thereafter recovered toward the initial level. Beginning at 2 weeks and continuing for an additional 2 weeks, maximal declines in dye penetrance of approximately 50% occurred with doses of INS365 as low as 1%. Such improvement in corneal epithelial resistance was accompanied by complete restoration of the PAS-stained area to the level seen in the control animal. CONCLUSIONS: In a rat dry eye model, the P2Y(2) agonist INS365 was found to improve surface health, based on increases in tear fluid secretion, corneal epithelial resistance, and release of glycoprotein-containing moieties from goblet cells. These effects suggest that INS365 is a potential therapeutic agent for use in the treatment of dry eye syndrome.

Animals↗
PubMed2001

Improvement of lacrimal function by topical application of CyA in murine models of Sjögren's syndrome.

PURPOSE: The object of this study was to evaluate improvement of lacrimal gland (LG) function after topical cyclosporin A (CyA). METHODS: Topical CyA (0.01% and 0.1%) was applied to two mouse models of Sjögren's syndrome, the NFS/sld after thymectomy and the nonobese diabetic (NOD) mouse, and the functional integrity of the lacrimal gland was evaluated by measuring basal and stimulated tear secretion and its histologic integrity by examining it for apoptosis and lymphocyte invasion. RESULTS: After treatment with CyA at 0.1% in the NFS/sld mice, tear function increased, and there was a decrease in lymphocyte infiltration of the LG and a decrease in apoptotic figures among the acinar cells. In the NOD mice, tear function also improved, but there was no associated decrease in lymphocyte infiltration. However, the expression of Fas ligand (FasL) in NOD mice by infiltrating lymphocytes was suppressed with 0. 1% CyA eye drops. CONCLUSIONS: CyA appears to improve tear secretion in mouse models of Sjögren's syndrome by preventing lymphocyte-induced apoptosis of acinar cells. In one model this was achieved by preventing lymphocyte infiltration and in the other by reducing expression of FasL expression on infiltrating lymphocytes.

Administration, Topical↗
PubMed2001

Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone.

The effect of pretreatment with dexamethasone (DEX) on drug-drug interactions between rhodamine 123 (Rho123), a P-glycoprotein (P-gp) substrate, and midazolam, a cytochrome P450 (CYP) 3A substrate, or verapamil, a P-gp/CYP3A substrate, was studied in rats. Rats were pretreated with DEX (100 mg/kg/day, oral) for 2 days. Western blot analysis with a monoclonal antibody for P-gp, C219, revealed that DEX pretreatment increased P-gp level in the intestine 1.9-fold, but not in the liver. In vitro metabolism study of erythromycin in microsomal suspensions indicated the 9.7-fold increase of CYP3A activity in the liver, but not in the intestine, by DEX pretreatment. In an in vivo study, DEX pretreatment increased P-gp-mediated exsorption clearance of Rho123 from blood to the intestinal lumen approximately 2-fold, but not biliary clearances, in good agreement with the results of Western blot analysis. In untreated rats, midazolam (100 microM) or verapamil (30 or 100 microM) added in the intestinal perfusate (single perfusion) decreased the exsorption clearance and biliary clearance of Rho123 by approximately 30 to 50%. In DEX-pretreated rats, however, the inhibitory potency of midazolam in the liver significantly decreased compared with that in untreated rats, although the potency in the intestine did not change. The inhibitory potency of verapamil decreased both in the intestine and liver by DEX pretreatment. In conclusion, it was demonstrated that DEX pretreatment affects not only P-gp-mediated disposition of Rho123 but also pharmacokinetic interactions of P-gp/CYP3A-related compounds with Rho123, probably because concentrations of substrates/inhibitors at target sites such as the intestine and liver are varied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Heat shock-mediated APX gene expression and protection against chilling injury in rice seedlings.

Rice (Oryza sativa L.) seedlings, when kept at 42 degrees C for 24 h before being kept at 5 degrees C for 7 d, did not develop chilling injury. Chilling resistance was enhanced in parallel with the period of heat-treatment. The level of APX activity was higher in heated seedlings whereas CAT activity was decreased by heat stress. There was no significant difference in SOD activity between heated and unheated seedlings. The elevated activity of APX was sustained after 7 d of chilling. The cytosolic APX gene expression in response to high and low temperature was analysed with an APXa gene probe. APXa mRNA levels increased within 1 h after seedlings were exposed to 42 degrees C. Elevated APXa mRNA levels could also be detected after 24 h of heating. The APXa mRNA level in preheated seedlings was still higher than unheated seedlings under cold stress. The promoter of the APXa gene was cloned from rice genomic DNA by TAIL-PCR, and characterized by DNA sequencing. The promoter had a minimal heat shock factor-binding motif, 5'-nGAAnnTTCn-3', located in the 81 bp upstream of the TATA box. Heat shock induction of the APXa gene could be a possible cause of reduced chilling injury in rice seedlings.

Ascorbate Peroxidases↗
PubMed2001

[A system of health education using dietary assessment].

We decided to focus attention on healthy young people, and to conduct a survey of their diet, as well as their physical activity and health condition, so that we made diagnoses and also give instructions on each subject using a computer program to promote their health. We carried out this experiment using this method with 836 young female subjects in order to find out whether it can be applied as a useful health education approach. 1. According to the survey, when the subjects made efforts in making the instructions as convenient as possible, the percentage of subjects who could carry out advice even 4 months later was seen to be higher. 2. The advice for which a significantly high percentage of subjects said "want to improve their daily action" and could actually carry out and improve them, was as follows: they should eat vegetables, have a substantial breakfast, drink milk every day, refrain from too much salt, not go without meals, increase the frequency of eating seaweed, and refrain from snacks. 3. The two kinds of scores used to evaluate diets showed that assessment after nine months gave lower values than those obtained when this survey started. Using these two evaluating scores, changes in diets were divided into five patterns, and their relation to the question "whether they used the advice or not" was examined. As a result, the percentage showing favorable diet changes in subjects who "took advice" was showed to be significantly high. 4. Subjects who received advice on physical activity exhibited improvement in carrying out routine exercises as well as making their daily life more active. 5. With subjects who took advice on both diet and physical activity, the number who complained about fatigue was significantly reduced. Although it is difficult to improve diet and exercise habits, the results of the survey suggest that our approach should be useful for improving health.

Adult↗
PubMed2001

Anchoring the Duran flexible annuloplasty ring with continuous sutures.

We practised a deviced method of anchoring the Duran flexible ring with continuous sutures. After passing through 3/0 monofilament sutures at the right and left fibrous trigones, both sutures are passed through the ring between the corresponding ring marker and continuous sutures are placed to attach the ring to the mitral valve annulus. This technique requires less time to anchor the ring than the original method with interrupted sutures and can prevent narrowing the mitral valve annulus following the deformity of the flexible ring. This technique can contribute to extend the indication of the prosthetic ring in mitral valve surgery.

Heart Valve Prosthesis Implantation↗
PubMed2001

Aortic valve replacement in a patient with factor XII deficiency: case report.

Congenital factor XII deficiency is a rare condition. We report a case of aortic valve replacement (AVR) in a 63-year-old man with factor XII deficiency. On admission, the patient's activated partial thromboplastin time (aPTT) was prolonged (271 s), and activated clotting time was 500 s. His factor XII level was <3%. The Sonoclot signature showed an abnormal pattern. AVR with a prosthetic valve (St. Jude Medical) was performed safely after the normalization of aPTT and the Sonoclot signature by frozen plasma transfusion. The perioperative management in patients with factor XII deficiency is discussed.

Aortic Valve↗
PubMed2001

Rapidly functional immobilization of immortalized human hepatocytes using cell adhesive GRGDS peptide-carrying cellulose microspheres.

With the development of biotechnology, hepatic support by a hybrid artificial liver (HAL) using hepatocytes has been given much attention. Because the availability of human livers is limited, we have established a tightly regulated immortal human hepatocyte cell line, NKNT-3, for developing HAL. Because high-density cell culture allows the compactness of the HAL device and its easy use under emergency circumstances, we have developed cell adhesive GRGDS peptide-containing cellulose microspheres (GRGDS/CMS). The GRGDS/CMS efficiently immobilized NKNT-3 cells within 24 h in a stirred suspension culture. Electron microscopic examinations demonstrated glycogen granules and well-developed endoplasmic reticulum and mitochondria in NKNT-3 cells attached to the GRGDS/CMS. The cells showed ammonia clearance activity, whereas HepG2-transformed human liver cells did not remove the loaded ammonia. An efficient adenoviral delivery of the lacZ reporter gene was performed in GRGDS/CMS-immobilized NKNT-3 cells. In this study we present rapid immobilization of NKNT-3 immortal human hepatocytes using cellulose microspheres carrying GRGDS peptides. These microspheres satisfied immediate preparation of NKNT-3 cells in sufficient quantity and of adequate quality.

Ammonia↗
PubMed2001

[Polyarteritis nodosa].

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Antibodies, Antineutrophil Cytoplasmic↗