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Biomedical subjects

Yoko Matsumoto

Publications and source records attributed to Yoko Matsumoto.

At least 19 recordsLinked to original sources
PubMed2006

Membrane targeted chemotherapy with hybrid liposomes for colon tumor cells leading to apoptosis.

A good correlation between 50% inhibitory concentration of hybrid liposomes (HL) composed of 90 mol% dimyristoylphosphatidylcholine and 10 mol% polyoxyethylene(n)dodecyl ether on the growth of human colon tumor (WiDr) cells, and membrane fluidity of HL was obtained. HL distinguished between WiDr and normal colon cells and then fused and accumulated into the membranes of WiDr cells leading to apoptosis.

Apoptosis↗
PubMed2006

Human homolog of Drosophila tumor suppressor Scribble negatively regulates cell-cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial cells.

Drosophila tumor suppressor Scribble has been identified as an apical-basolateral polarity determinant in epithelia. A human homolog of Drosophila Scribble, human Scribble (hScrib), has been identified as a protein targeted by human papillomavirus E6 for the ubiquitin-mediated degradation dependent on E6AP, a cellular ubiquitin-protein ligase. Human Scribble is classified as a LAP protein, having leucine-rich repeats (LRRs) and PDZ domains. We investigated whether hScrib, which is thought to have a role in polarity determination based on the data of its Drosophila homolog, is involved in cell-cycle regulation and proliferation control of epithelia. Transfection of hScrib inhibits cell-cycle progression from G1 to S phase, and it up- and down-regulates expression of adenomatous polyposis coli and cyclins A and D1, respectively. Knockdown of hScrib expression by siRNA leads to cell-cycle progression from G1 to S phase. We explored functional domain mapping to reveal which domains of hScrib are critical for its cellular proliferation control and localization at the basolateral membrane. We found that LRRs and PDZ domain 1 are indispensable for hScrib to inhibit cell growth by blocking cell-cycle progression and to keep its proper localization. These data indicate that basolateral membrane localization of hScrib is closely related to its proliferation control. Our findings suggest the possibility that hScrib is involved in signal transduction to negatively regulate cell proliferation by localizing at the basolateral membrane of epithelial cells through LRRs and PDZ domains.

Animals↗
PubMed2006

Chemotherapy with hybrid liposomes for lymphoma without drugs in vivo.

Hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (n) dodecyl ether (C(12)(EO)(n), n=21 and 25) were prepared with the method of sonication. Clear solution of hybrid liposomes having hydrodynamic diameter of 80-100 nm could be maintained over 3 weeks. Hybrid liposomes induced apoptosis for human lymphoma (MOLT-4 and RAJI) cells in vitro. No toxicity was observed in the rats after intravenously injecting hybrid liposomes in vivo. We clearly demonstrated that a mouse model of lymphoma was established and prolonged survival was obtained in mice models of lymphoma after the treatment with hybrid liposomes without drugs in vivo. The results in this study should support the prolonged survival for patients with lymphoma in clinical applications.

Animals↗
PubMed2006

Involvement of a cellular ubiquitin-protein ligase E6AP in the ubiquitin-mediated degradation of extensive substrates of high-risk human papillomavirus E6.

Human scribble (hScrib), which was identified as substrate of human papillomavirus (HPV) E6 for ubiquitin-mediated degradation dependent on ubiquitin-protein ligase E6AP, is a human homolog of Drosophila neoplastic tumor suppressor scribble, in which mutation causes loss of polarity and overgrowth of epithelia. Drosophila discs large (Dlg) is one of neoplastic tumor suppressors, which genetically links to scribble. E6 also targets human Dlg (hDlg) for ubiquitin-mediated degradation. Ubiquitin-protein ligase involved in this process has not been identified thus far. Here we investigated mechanism underlying degradation of three target proteins of E6, hScrib, hDlg, and p53 by using eighteen HPV 16 E6 mutants with single amino acid substitution. In vitro degradation ability of each E6 mutant was equivalent for these tumor suppressors. We investigated whether E6AP is involved in ubiquitin-mediated degradation of hDlg. In vitro binding assay revealed that hDlg formed ternary complex with E6-E6AP complex. The ability of E6 mutants to degrade these tumor suppressors was correlated with their ability to interact with E6AP. Furthermore, hDlg was targeted for in vitro ubiquitination in the presence of both E6 and E6AP. These data revealed that E6AP is extensively involved in the ubiquitin-mediated degradation of E6-dependent substrates as a cellular E3 ubiquitin-protein ligase.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Production of antitumor substances from shochu distillation remnants].

This study aimed to develop a new processing method for the effective use of rice shochu distillation remnants. We examined the inhibitory effects on the growth of human lung carcinoma cells in the medium of rice shochu distillation remnants with various fungi. Interestingly, high inhibitory effects on the growth of human lung carcinoma cells in the medium of rice shochu distillation remnants with Aspergillus oryzae were obtained, although no inhibitory effect was observed in the case of synthetic medium. We therefore fractionated the medium of rice shochu distillation remnants with A. oryzae using anion-exchange and reverse-phase chromatography. Furthermore, we attempted to determine the chemical structure of compounds that showed high inhibitory effects on the growth of tumor cells. The chemical structure of 1-hydroxy-6-(1-methylpropyl)-3-(2-methylproryl)-2(1H)-pyrazinone was revealed on the basis of liquid and gas mass spectroscopies. This compound should be completely safe based on toxic test results using model mice.

Animals↗
PubMed2006

[Pulsation in polypoidal choroidal vasculopathy].

PURPOSE: To evaluate the relationship between pulsation and the fundus lesion in polypoidal choroidal vasculopathy (PCV). OBJECTIVE AND METHODS: We studied 26 eyes with PCV by indocyanine green angiography (IA) with a heidelberg retina angiograph(HRA). The 26 eyes were classified into two groups; pulsatile PCV and non-pulsatile PCV. We evaluated the strength and the amplitude of the pulsation, and the frequency of subretinal hemorrhage within one year after the first IA. Seven eyes in the pulsatile PCV group were tested by HRA twice or more to evaluate the relationship between the fundus lesion and the change in the strength and the amplitude of pulsation. RESULTS: Subretinal hemorrhage occurred in 9 of 14 eyes with pulsatile PCV and in 2 of 12 eyes with non-pulsatile PCV (odds ratio : 12.5). The possibility of subretinal hemorrhage was significantly higher in pulsatile PCV than in non-pulsatile PCV. In 3 of the 7 eyes tested twice or more, the fundus lesion worsened as the pulsation strengthened and the area of pulsation enlarged. In 1 of the 7 eyes, the fundus lesion improved as the pulsation weakened and the area of pulsation decreased. CONCLUSION: There is a good possibility that strengthened and extended pulsation is related to increasing subretinal hemorrhage in PCV patients.

Aged↗
PubMed2006

[Clinical effects of photodynamic therapy with Verteporfin for age-related macular degeneration 1: three-month results].

PURPOSE: To evaluate the 3-month effects after one-time photodynamic therapy (PDT) for subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). SUBJECTS AND METHODS: The subjects were 122 patients with subfoveal CNV due to AMD detected by fluorescein angiography (FA). FA, indocyanine-green angiography (IA), and the examination of visual acuity were done before and 3 months after PDT. The diameter of CNV in FA was compared, and ophthalmological examination before the treatment determined whether there were any factors associated with a reduction or suppression of CNV. RESULTS: 3 months after PDT, 89 eyes had a significant (p < 0.001) reduction of CNV (41 eyes had blockage of CNV). In case of polypoidal choroidal vasculopathy (PCV) detected by IA, CNV was significantly reduced compared with the effects of other types of therapy (p = 0.032). Moreover, CNV was blocked significantly when fibrin tissue was present on a part of CNV before treatment (p = 0.026). Visual acuity was maintained or improved in 96 eyes. CONCLUSION: One-time PDT was effective in reducing or suppressing CNV as confirmed by FA.

Aged↗
PubMed2006

[Assessment of the quality of life of patients with age-related macular degeneration after photodynamic therapy].

OBJECTIVE: To quantify quality of life (QOL) changes in patients who have received a single session of photodynamic therapy (PDT) for subfoveal choroidal neovascularization, secondary to age-related macular degeneration (AMD), and to identify factors that correlate with the QOL changes. METHODS: The QOL changes in 88 patients with AMD were scored with the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) before and 3 months after a single PDT with routine ophthalmologic examinations. We used multiple regression analysis to evaluate VFQ-25 sub-scale scores and ophthalmologic findings in these patients before PDT, to identify impact on the effectiveness of PDT. We also evaluated changes in ophthalmologic findings influencing the QOL score. RESULTS: The sub-scale scores for both 'mental health' (p = 0.02) and 'role limitation' (p = 0.03) improved significantly in all 88 cases, but only 'mental health' improved significantly in 34 cases in which PDT was effective. Multiple regression analysis in all 88 cases revealed that the factors contributing significantly to improvement in 'mental health' were a lower pre-PDT 'mental health' score (p < 0.01) and the presence of fibrous tissue (p = 0.01) before the PDT session. The lower the role limitation before PDT (p < 0.01), the more significant was the improvement in this score. CONCLUSION: Although no baseline sub-scale score was identified as predicting the effectiveness of a single PDT session, the scores for both 'mental health' and 'role limitation' improved.

Aged↗
PubMed2005

Two methylene groups in phospholipids distinguish between apoptosis and necrosis for tumor cells.

High inhibitory effects of hybrid liposomes (HL) themselves composed of DMPC/10 mol% C12(EO)23 on the growth of HL-60 cells were obtained without any drug. Induction of apoptosis was obtained by the HL of DMPC/10 mol% C12(EO)23. On the other hand, necrosis was observed for the HL of DLPC/10 mol% C12(EO)23. In the case of DPPC/10 mol% C12(EO)23, neither apoptosis nor necrosis was observed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Novel mechanism of hybrid liposomes-induced apoptosis in human tumor cells.

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity, phase transition temperature and hydrophobicity can be controlled by changing the composition. Hybrid liposomes composed of dimyristoylphosphatidylcholine and polyoxyethylene (10) dodecyl ether were found to inhibit the growth of human promyelocytic leukemia (HL-60) cells without using any drugs. Induction of apoptosis by hybrid liposomes in HL-60 cells was verified on the basis of fluorescence microscopy and flow cytometry analysis, after fusion and accumulation of hybrid liposomes, which was revealed on the basis of microphysiometer. We elucidated the pathways of apoptosis induced by the hybrid liposomes. That is, hybrid liposomes fused and accumulated in tumor cell membranes, and the apoptosis signal first passed through mitochondria, caspase-9 and caspase-3, second through Fas, caspase-8, caspase-3 and then reached the nucleus. Hybrid liposomes themselves can induce apoptosis in human tumor cells along with high inhibitory effects on the growth of tumor cells.

Antineoplastic Agents↗
PubMed2005

Induction of apoptosis of human lung carcinoma cells by hybrid liposomes containing polyoxyethylenedodecyl ether.

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in aqueous solution. A clear solution of hybrid liposomes composed of 90 mol% dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene(23)dodecyl ether (C12(EO)23) having a hydrodynamic diameter of 100-120 nm was obtained. Highly inhibitory effects of hybrid liposomes of 90 mol% DMPC/10 mol% C12(EO)23 on the growth of human lung carcinoma (RERF-LC-OK and A549) cells without any drugs were obtained. Induction of apoptosis by hybrid liposomes in RERF-LC-OK and A549 cells was verified on the basis of fluorescence microscopy, agarose gel electrophoresis of DNA and flow cytometry. We elucidated the pathway of apoptosis induced by hybrid liposomes as follows: (a) accumulation of hybrid liposomes in tumor cell membrane was revealed using microphysiometer. (b) Reduction of mitochodrial membrane potential and activation of caspase-9, -3 and -8 were obtained, indicating that apoptotic signal by hybrid liposomes should pass through mitochondria and these caspases. It is worthy to note that such a novel mechanism of apoptosis induced by hybrid liposomes without any drugs was performed for the first time in human lung carcinoma cells.

Biosensing Techniques↗
PubMed2004

Enzymatic and hyperglycemia stability of chemically modified insulins with hydrophobic acyl groups.

The acylated insulins were synthesized by the reaction of insulin protected by p-methoxybenzoxy carbonyl azide at Gly-A1 site with N-hydroxysuccinimide ester of caproic acid or benzoic acid (Cap-insulin and Bz-insulin). The noteworthy aspects are as follows: (a) the acylated insulins were more stable to the decomposition by various digestive enzymes as compared with native insulin in vitro. (b) Animal experiments using normal rats in vivo revealed that the Bz-insulin had an effective hypoglycemia activity almost similar to that of native insulin.

Animals↗
PubMed2004

Rare case of the inferior mesenteric artery and the common hepatic artery arising from the superior mesenteric artery.

We found a case in which inferior mesenteric artery and the common hepatic artery arose from the superior mesenteric artery, forming the common hepatomesenteric trunk, during a routine dissection carried out at Iwate Medical University in 2002. This variation is rare, but can be embryonically explained. A change in the positions of the disappearance of the ventral splanchnic arteries and the longitudinal anastomotic channel results in variations in the system of arteries distributed to the digestive organs. In the present case, the longitudinal anastomotic channel between the superior and the inferior mesenteric arteries survived to form the common mesenteric artery, which was joined by the common hepatic artery, forming the common hepatomesenteric trunk.

Aged↗
PubMed2004

Pars plana suture fixation for intraocular lenses dislocated into the vitreous cavity using a closed-eye cow-hitch technique.

We describe a modified intraocular cow-hitch technique for pars plana suture fixation of intraocular lenses (IOLs) that dislocated into the vitreous cavity in 3 patients who had a 3-port vitrectomy and IOL implantation because of retinal disease. To reposition the dislocated IOL after the residual vitreous was removed, 2 additional sclerotomies for suture fixation were made 3.0 mm posterior to the limbus. A loop (cow-hitch knot) was made with 10-0 polypropylene for suture fixation. After the neck of the cow-hitch loop was grasped with an intraocular forceps, the loop was used to lasso a haptic of the dislocated IOL, which was then pulled forward to the sclerotomy. The same procedure was used for the other haptic, and both sutures were secured to the sclera under scleral flaps. In all patients, the dislocated IOLs were repositioned without the need for extraction. The procedures were uneventful. Pars plana suture fixation with the intraocular cow-hitch technique can be used to reposition an IOL that has dislocated into the vitreous cavity.

Adult↗
PubMed2004

Modulation of actomyosin motor function by 1-hexanol.

This study examines the effects of 1-hexanol as a perturbing agent on actomyosin ATPase and its related functions in the concentration range between 0 and 20 mM. In this range the denaturation of myosin subfragment 1 (S1), as measured by the inactivation rate of its K-EDTA-ATPase, and depolymerization of F-actin were insignificant. Major findings showed that hexanol had the following effects which were fully reversible, (a) a marked activation of S1 MgATPase (approximately 10-fold at 20 mM) without greatly affecting the enhancement of tryptophan fluorescence by formation of S1.ADP.Pi intermediate and the rate of ADP release from S1.ADP; (b) an inhibition of the maximum actin-activated ATPase activity; (c) an increase in the affinity of S1 for actin in the presence of ATP and a decrease in the presence of ADP or the absence of nucleotide; (d) a reduction in the sliding velocity of actin filaments in in vitro motility assays with myosin, and (e) a decrease in isometric tension of single skinned muscle fibers. Thus, the effects of hexanol on actomyosin interaction are distinct for the weak and strong binding states, consistent with a change in the hydrophobic interaction in the interface between myosin and actin accompanying the transition from the weak to the strong binding state. Hexanol also accelerates the Pi release from S1.ADP.Pi, which is the transition step from the weak to the strong binding state. The fact that hexanol accelerates Pi release suggests that this alcohol perturbs the S1.ADP.Pi conformation. We speculate that this intermediate-specific structural perturbation is related to the inhibition of the maximum actin-activated ATPase, in vitro motility, and isometric tension.

Actins↗
PubMed2004

Inhibitory effects of extracts from peels of Citrus natsudaidai encapsulated in hybrid liposomes on the growth of tumor cells in vitro.

Inhibitory effects of extracts from peels of Citrus natsudaidai (natsumikan) encapsulated in hybrid liposomes (HL) composed of L-alpha-dimyristoylphosphatidylcholine and polyoxyethylene (20) sorbitan monolaurate on the growth of tumor cells were examined. The extracts with lower polar solvents inhibited the growth of B-16 mouse melanoma and human lung carcinoma cells, although the extracts with higher polar solvents showed no antitumor activity. In particular, the inhibitory effects of extracts with lower polar solvents encapsulated in HL were enhanced as compared with those of free extracts. Fluorescence microscopic analysis indicated that the HL including petroleum ether extracts induced apoptosis in B-16 mouse melanoma cells. On the other hand, the viability of normal human fibroblast cells was even less affected by the extracts of natsumikan. These results suggest that hydrophobic antitumor agents should be present in peels of natsumikan.

Adenocarcinoma↗
PubMed2004

[Hybrid liposomes as a drug carrier for the oral administration of insulin in diabetic rats].

It is known that hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and micellar surfactant (Tween 20) are effective for encapsulating drugs and for the treatment of meningeal gliomatosis in vivo without toxicity. In this study, we attempted to use these hybrid liposomes as a drug carrier system for the oral administration of insulin using diabetic model rats. The noteworthy aspects were as follows: (a) The hybrid liposomes of 90 mol% DMPC/10 mol% Tween 20 were stable and uniform for more than 4 weeks. (b) The blood glucose level of diabetic model rats decreased after the oral administration of hybrid liposomes including insulin. These results suggest that the oral administration of hybrid liposomes including insulin should be effective for the treatment of diabetes.

Administration, Oral↗