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T Mayumi

Publications and source records attributed to T Mayumi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Enhanced in vitro percutaneous penetration of salicylate by ion pair formation with alkylamines.

The apparent octanol/water partition coefficient (APC) of salicylate (SA) increased as the concentration of alkylamine (amyl, hexyl, heptyl, octyl and nonylamine) in aqueous phase increased, presumably through intermolecular ion pair formation between the negatively charged SA moiety and the alkylamine cation. The true partition coefficient (TPC) and the formation constant (Kf) of the ion pair were calculated from the partition data. The skin permeability of SA increased as the APC of SA increased, when 20-fold molar excess of alkylamine was added to the donor compartment. Permeability of ion pairs (PAB) from the aqueous phase to a shed snake skin was estimated from the permeability data assuming 1:1 ion pair. The methylene group contribution to the free energy of transfer of ion pairs from water to the shed snake skin was less than the reported value for nonionized drugs. This suggests that the ion pair is more polar by nature than nonionized molecules, even if ionic characteristics are masked to some extent by ion pair formation.

Amines↗
PubMed1998

Amino acids and peptides. XXXI. Preparation of analogs of the laminin-related peptide YIGSR and their inhibitory effect on experimental metastasis.

Analogs of a partial sequence peptide of laminin, i.e., Tyr-Ile-Gly-Ser-Arg (YIGSR) analogs and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg (CDPGYIGSR) analogs, were prepared by the solid-phase method and their inhibitory effects on experimental metastasis of B16-BL6 melanoma cells were examined. YIGSR analogs in which Ile was replaced by other hydrophobic amino acids (Met, Leu, Phe) were inhibitory. Cys-containing analogs of YIGSR were also prepared, but were less active than the parent peptide, YIGSR. Among them, CYIGSR was easily oxidized to form a disulfide bond. A Cys-containing YIGSR analog cyclized through a disulfide bond, cyclo(CYIGSRC)G, was prepared. The disulfide bond formation was performed on the resin by the silyl chloride-sulfoxide method and by the iodine oxidation method. The yield of the silyl chloride-sulfoxide method was much better than that of the iodine oxidation method.

Animals↗
PubMed1998

Total structures of colistin minor components.

Structural characterization of the colistin (CL) components were carried out using Frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS), tandem mass spectrometry (MS/MS) and the amino acid analysis proposed by MARFEY, and the total structures of 4 minor components including the absolute configuration of the constituent amino acids were proposed. The structures of the minor components were the same as those of the main component colistin A or B except that L-leucine is replaced by L-valine or L-isoleucine.

Anti-Bacterial Agents↗
PubMed1998

[Molecular design of polymer-conjugated cytokines and its application for drug delivery systems].

In recent years, clinical application of recombinant cytokines has been expected as a novel drug for various diseases. However, cytokines have generally poor stability in vivo, so they required of very high doses to achieve sufficient clinical effect. In addition, because cytokines have pleiotropic functions, they would cause unfavourable side-effects. Therefore an drug delivery system (DDS) is necessary for clinical use, which stabilizes the cytokines and potentiates only the expected function from other unfavorable ones in vivo. Then we performed the chemical modification of cytokines with water-soluble polymers to overcome such problems as poor stability and pleiotropic activities. This approach includes some advantages that decrease renal excretion rate of proteins and prevent the degradation by proteases. This would result in prolonging the half-lives of bioactive proteins and potentiating their clinical effects. Interestingly, we found that the polymer-conjugated cytokines, that we named hybrid-cytokines, for instance, polyethylene glycol-modified interleukin-6 (PEG-IL-6), were able to increase selectively in their function of promoting platelet production, but not in other unfavourable functions. This effects were suggested for a result of the change in the systemic distribution pattern by pegylation of proteins. In this review, we proposed that the DDS using hybrid-cytokines would be able to increase the stability and regulate the spectrum of the functions of the cytokines by controlling the pharmacokinetics and pharmacodynamics in vivo. This will provide a fundamental information enabling us to design the hybrid-proteins applicable to therapeutic use.

Cytokines↗
PubMed1997

Amino acids and peptides. XXXII: A bifunctional poly(ethylene glycol) hybrid of fibronectin-related peptides.

An amino acid type poly(ethylene glycol) (aaPPEG) was prepared and its application to a drug carrier was examined. The peptides, Arg-Gly-Asp (RGD) and Glu-Ile-Leu-Asp-Val (EILDV) which were reported as active fragments of Fibronectin (a cell adhesion protein), were conjugated with aaPEG (molecular weight, 10,000). The hybrid, RGD-aaPEG-EILDV, was prepared by a combination of the solid-phase method and the solution method. Antiadhesive activity of the peptides was not lost by its hybrid formation with the large aaPEG molecule. A mixture of RGD (0.43 mmol) and EILDV (0.43 mmol) did not demonstrate an antiadhesive effect, but the hybrid containing 0.43 mmol of each peptide did exhibit this effect.

Carrier Proteins↗
PubMed1997

Positively charged liposome functions as an efficient immunoadjuvant in inducing immune responses to soluble proteins.

To design an optimum liposome immunoadjuvant for soluble protein antigens, we investigated the relationship between liposomal surface charge and adjuvant action. Positively charged multilamellar vesicles (MLV) were taken up efficiently by macrophages, while negatively charged and neutral MLVs were hardly picked up. Consistent with this, positively charged MLVs containing soluble chicken egg albumin (OVA) functioned as a more potent inducer of antigen-specific cytotoxic T lymphocyte (CTL) responses and antibody production than negatively charged and neutral MLVs containing the same concentrations of antigens. These results indicate that the positive charge on the surface of liposomes represents an important factor for enhancing their immunoadjuvancy in the induction of antigen-specific immune responses.

Adjuvants, Immunologic↗
PubMed1997

Bioconjugation of tumor necrosis factor-alpha with the copolymer of divinyl ether and maleic anhydride increasing its antitumor potency.

To enhance the therapeutic usefulness of antitumor cytokines in vivo, we synthesized bioconjugated tumor necrosis factor-alpha (TNF-alpha) with divinyl ether and maleic anhydride copolymer (DIVEMA), which has intrinsic antitumor activity as a synthetic biological response modifier. The degree of modification could be controlled by the addition of 2,3-dimethylmaleic anhydride (DMMAn), which binds to amino groups of TNF-alpha by changing the pH. In addition, the specific activity of DIVEMA-TNF-alpha was hardly decreased in vitro. DIVEMA-TNF-alpha showed a marked antitumor effect compared to native TNF-alpha without any side effects such as sudden death, body-weight reduction, and decrease in platelet count on mice bearing solid tumors. These results suggest that DIVEMA is a useful polymeric modifier for-bioconjugation of TNF-alpha in order to increase its antitumor activity, and multifunctionally bioconjugated TNF-alpha may be a potentiated antitumor agent for therapeutic use.

Animals↗
PubMed1997

Antibody-based therapy targeting tumor vascular endothelial cells suppresses solid tumor growth in rats.

We have developed a new approach to antibody-based therapy of solid tumors by targeting tumor vascular endothelial cells (EC) which are essential for the growth of solid tumors. We investigated the effect of an antibody against tumor-derived endothelial cells (TEC) on the growth of solid tumors in rats. Intravenous administration of TES-23, a monoclonal antibody generated by TEC isolated from rat KMT-17 solid tumors, at 1 mg/rat/day for 5 days resulted in significant suppression of KMT-17 tumor growth. Histopathological analysis of tumors administered with TES-23 showed that adhesion of lymphocytes to EC followed by denudation of EC in the viable tumor area. In contrast, little obvious toxicity was observed in most of the rat organs examined. These findings suggest that the concept of an antibody-based therapy with targeting tumor vascular EC would be promising in treatment of solid tumors.

Animals↗
PubMed1997

A novel type of calcium channel sensitive to omega-agatoxin-TK in cultured rat cerebral cortical neurons.

We characterized the electrophysiological properties of calcium channels in cultured rat cerebral cortical neurons using omega-agatoxin-TK (omega-Aga-TK) by a patch-clamp technique. Two types of slowly inactivating calcium channels sensitive to omega-Aga-TK were detected. The first type showed high sensitivity to omega-Aga-TK and low recovery from the omega-Aga-TK-induced blockade during washout, corresponding to the P-type channel. The second type showed low sensitivity to omega-Aga-TK and high recovery, resembling the Q-type channel, although it was distinct from the Q-type in terms of slower inactivation kinetics. We designate this channel as Q(L)-type (long-lasting Q channel). The omega-Aga-TK-sensitive calcium channels involved in the glutamatergic synaptic transmission were also divided into two types based on the sensitivity to omega-Aga-TK and reversibility of omega-Aga-TK-induced blockade. We conclude that the Q(L)-type is a novel type of channel, and that both P-type and Q(L)-type channels play a significant role in the cerebral cortical synaptic transmission.

Agatoxins↗
PubMed1997

Cytoplasmic gene expression system enhances the efficiency of cationic liposome-mediated in vivo gene transfer into mouse brain.

Development of methodologies for gene transfer into the central nervous system (CNS) is important for fundamental research as well as clinical studies for gene therapy. Cationic liposomes (CL) are attractive vectors because of their safety and ease of use. However, to date only low rates of success have been reported. We succeeded in obtaining high transfection efficiencies into the newborn mouse brain in vivo by CL and a cytoplasmic gene expression system based on T7 RNA polymerase and T7 RNA polymerase- and the luciferase-gene with the T7 promoter sequence. This system showed an efficiency rate 2 orders of magnitude higher than the standard system, which used CL and luciferase genes with a Rous sarcoma virus promoter, pRSVL. In addition, in vitro experiments using LLCMK2 cells showed that cytoplasmic gene expression occurred rapidly (within 6 h) after transfection. In contrast, pRSVL required 24-48 h for induction of luciferase expression. Our results suggest that the cytoplasmic gene expression system is useful for gene delivery into the CNS.

Animals↗
PubMed1997

Cytomedical therapy for IgG1 plasmacytosis in human interleukin-6 transgenic mice using hybridoma cells microencapsulated in alginate-poly(L)lysine-alginate membrane.

Cytomedical therapy for human interleukin-6 transgenic mice (hIL-6 Tgm) was implemented by the intraperitoneal injection of alginate-poly(L)lysine-alginate (APA) membranes microencapsulating SK2 hybridoma cells (APA-SK2 cells) which secrete anti-hIL-6 monoclonal antibodies (SK2 mAb). IgG1 plasmacytosis in the hIL-6 Tgm was suppressed by a single injection of APA-SK2 cells, and the survival time of these mice was remarkably prolonged. The viable cell number and the SK2 mAb-secretion of APA-SK2 cells increased for at least one month both under culture conditions and in allogeneic recipients (in vivo). Moreover, SK2 mAb which were secreted from APA-SK2 cells injected into allogeneic recipients was detected in serum at high concentrations; 3-5 mg/ml from day 14 to day 50 post-injection. In contrast, the injection of free SK2 cells had no therapeutic effect on hIL-6 Tgm. These results strongly suggest that APA membranes microencapsulating cells which were modified to secrete molecules useful for the treatment of a disorder were effective as an in vivo long-term delivery system of bioactive molecules, as 'cytomedicine'.

Alginates↗
PubMed1997

Immunological studies of SK2 hybridoma cells microencapsulated with alginate-poly(L)lysine-alginate (APA) membrane following allogeneic transplantation.

Microencapsulation of living cells or tissues has been proposed to prevent their immune destruction following transplantation. In this study, we examined whether SK2 hybridoma cells microencapsulated in an alginate-poly(L)lysine-alginate (APA) membrane (APA-SK2 cells) were immunoisolated from the allogeneic host's immune system using a cytotoxicity test. The APA membrane inhibited the activation of the host's cellular immune response, but did not prevent the production of cytotoxic antibodies against entrapped SK2 cells following allogeneic transplantation. However, the APA-SK2 cells remained vital in SK2 cell-immunized mice as well as in intact mice. We considered that complement regulatory factors which were present on cell membrane and had species-specific restriction blocked the complement-mediated cell lysis on allogeneic transplantation, since APA-SK2 cells were destroyed by rabbit anti-SK2 cell antiserum. Our results demonstrated that APA membrane could inhibit cell-cell contact between entrapped cells and the host's lymphocytes, but could not completely protect the entrapped cells from xenogeneic humoral immunity.

Adoptive Transfer↗
PubMed1997

Distal pancreatectomy with en bloc resection of the celiac artery for carcinoma of the body and tail of the pancreas.

CONCLUSION: Combined resection of the celiac artery with a distal pancreatectomy (DP) increases the resectability and improves the overall prognosis of patients with locally advanced ductal cancer of the body and tail of the pancreas. BACKGROUND: Carcinoma of the body and tail of the pancreas is often unresectable because of invasion to adjacent organs. We evaluated a DP including an en bloc resection of the celiac artery ("extended"), for pancreatic cancer that had invaded the common hepatic and/or celiac arteries. METHODS: Six cases of an "extended" DP were compared with 19 cases of a "standard" DP for pancreatic ductal carcinoma in terms of clinical and pathologic findings, perioperative course, and long-term outcome. We also compared the survival rate of these two groups with a third group consisting of 22 patients with unresectable pancreatic ductal carcinoma. RESULTS: The mean operative time, postoperative serum aspartate aminotransferase concentration, and length of hospital stay did not significantly differ between the "extended" and "standard" DP groups. The cumulative 1- and 3-yr accumulated survival rates for the "extended," "standard," and unresectable groups were 40.0, 33.3, and 5.4, and 20.0, 16.6, and 0%, respectively. Statistically significant differences (p < 0.01) existed between the "extended" and unresected groups.

Adult↗
PubMed1997

Preparation of glial extracellular matrix: a novel method to analyze glial-endothelial cell interaction.

Studies on the interactions of endothelial cells and glial cells are of increasing importance for the understanding of the formation of the blood-brain barrier (BBB) and for the reconstruction of BBB properties in cultured brain capillary endothelial cells in vitro. Many methods have been used to examine cell-cell interactions, including conditioned medium, co-culture, feeder layers, and many others. Here we describe how to prepare the extracellular matrix (ECM) secreted from cultured cells. Cells are known to produce and interact with their extracellular components in an organized matrix and to regulate the function of other cells through the ECM. The ECM plays a central role in the differentiation and function of the cells, and controls the proliferation and motility of these cells. The responses of cells to ECM molecules need to be clarified. As the ECM is situated between cerebral capillaries and astrocytes in the central nervous system, the ECM secreted by glial cells may also play an important role in the formation and maintenance of the BBB. In our previous studies, the ECM produced by glial cells elevated gamma-glutamyl transpeptidase activity, which is an accepted marker enzyme for differentiated brain capillary endothelial cells, in cultured bovine brain capillary and aortic endothelial cells. Using the method described here, the cell-cell interaction via the ECM molecules can be examined.

Alkaline Phosphatase↗
PubMed1997

Comparison of tympanic, esophageal and blood temperatures during mild hypothermic cardiopulmonary bypass: a study using an infrared emission detection tympanic thermometer.

OBJECTIVE: Tympanic temperature can be obtained instantaneously using an infrared emission detection (IRED) thermometer. Its accuracy has been documented in a variety of clinical settings, but its performance at low body temperatures is still unknown. In this study we evaluated its performance during coronary artery revascularization surgery in which mild hypothermic cardiopulmonary bypass (CPB) was used. METHODS: Thirty adult patients undergoing coronary artery bypass graft surgery were enrolled in the study. Tympanic temperature obtained using IRED thermometry (Tt1) was compared with core temperatures from the esophagus (Te), and venous blood of CPB (Tv) before, during, and after CPB. We also measured tympanic temperature using a thermocouple probe (Tt2) in 16 of the 30 patients in order to study the agreement between the two methods. Values for correlation coefficients and limits of agreement were computed to assess the degree of agreement among the temperatures obtained. RESULTS: The highest agreement with Tv during CPB was obtained from Tt1 (r = 0.94, 0.41 +/- 1.73, limits of agreement) and from Te (0.91, 0.36 +/- 2.46). Tt1 also showed good agreement with Tt2 during surgery. CONCLUSIONS: Infrared tympanic thermometry is a reliable, alternative method to measure tympanic temperature and may be useful to assess core temperature in both normothermic and mild hypothermic conditions.

Adult↗
PubMed1997

Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 microgram/ml; 0.44 microM) inhibited human neutrophil or T cell adhesion to tumor necrosis factor-alpha (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Proliferative effect of dextran sulfate sodium (DSS)-pulsed macrophages on T cells from mice with DSS-induced colitis and inhibition of effect by IgG.

The authors have previously reported that homologous immunoglobulin (Ig)G reduces the occurrence of dextran sulfate sodium (DSS)-induced colitis, mainly by suppressing recruitment of immunocompetent cells into colitis lesions. However, the mechanisms of cell recruitment and of its suppression by IgG remain unclear. In addressing these questions, this study focused on the activation of T cells in the presence of macrophages. The authors found that [3H]-thymidine uptake of T cells from DSS-induced colitis mice, but not from normal mice, was significantly enhanced when cultured with DSS-pulsed macrophages. From the profile of cytokine production, it was suggested that T helper 1 (Th1)-type cells become predominant during stimulation. Addition of homologous IgG significantly suppressed T cell proliferation in a dose-dependent manner, while no suppressive effect was observed with heterologous IgG. Mouse IgG F(ab')2, but not Fc, fragments partially mimicked the suppressive effect of whole IgG. These findings provide evidence that Th1-type cells may play an important role in the development of DSS-induced colitis and that homologous IgG exerts its protective action at least in part through the F(ab')2 portion.

Animals↗