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Biomedical subjects

Kenji Kono

Publications and source records attributed to Kenji Kono.

17 recordsLinked to original sources
PubMed2005

[Spinal cord metastases in lung cancer: a clinical review of four cases].

We report 4 cases of spinal cord metastases of lung cancer detected by MRI. Histologically, 3 of the 4 cases were small cell carcinoma and the other was adenocarcinoma. All 3 cases of small cell carcinoma had neoplastic meningitis. MRI taken in these cases showed the multiple nodules in the cauda equina, which were seeded from brain metastases. One of them had intramedullary spinal cord metastases, which appeared as enlargement of the spinal cord or nodules in the spinal cord on MRI. Leg paralysis and incontinence progressed in all cases. The other case of adenocarcinoma had epidural spinal cord compression due to spinal metastasis. In this case irradiation and corticosteroids relieved her leg and back pain. Spinal cord metastases should be considered as a differential diagnosis in patients with numbness, pain or weakness in the extremities.

Adenocarcinoma↗
PubMed2005

[A case of sarcoidosis with diffuse pulmonary arteriovenous malformations].

A 27-year-old woman was admitted because of right dry eye and blurred vision. She was given a diagnosis of uveitis due to sarcoidosis. Chest X-ray film showed bilateral hilar lymphadenopathy and multiple nodules in both lungs. The nodules were considered to be associated with sarcoidosis. However chest CT demonstrated that the nodules were well-defined and connected with two vessels. We diagnosed diffuse pulmonary arteriovenous malformations (AVMs) by 3D-CT. In three of sixteen AVMs, the feeding vessels were more than 3 mm wide in diameter on pulmonary arteriography, and those were embolized by platinum coils. The embolotherapy of diffuse AVMs could not ameliorate the shunt fraction sufficiently, but should reduce the possibility of the catastrophic complication of brain abscess.

Adult↗
PubMed2004

Rendering poly(amidoamine) or poly(propylenimine) dendrimers temperature sensitive.

The poly(amidoamine) dendrimers having terminal isobutyramide (IBAM) groups were prepared by the reaction of isobutyric acid and the amine-terminated poly(amidoamine) dendrimers with generations (G) of 2 to 5 by using a condensing agent, 1,3-dicyclohexylcarbodiimide. 1H and 13C NMR revealed that an IBAM group was attached to essentially every chain end of the dendrimers. While the IBAM-terminated G2 dendrimer was soluble in water, the IBAM-terminated G3, G4, and G5 dendrimers exhibited the lower critical solution temperatures (LCSTs) at 75, 61, and 43 degrees C, respectively. Because the density of the terminal IBAM groups in the periphery of the dendrimer progressively increases with increasing dendrimer generation, the interaction of the IBAM groups might take place more efficiently, resulting in a remarkable decrease in the LCST. In addition, attachment of IBAM groups to poly(propylenimine) dendrimers could give the temperature-sensitive property, indicating that this is an efficient method to render dendrimers temperature sensitive.

Journal Article↗
PubMed2004

Accumulation of boron compounds to tumor with polyethylene-glycol binding liposome by using neutron capture autoradiography.

The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B atoms to the tumor cells selectively for effective BNCT. In order to achieve an accurate measurement of 10B concentrations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of the sliced whole-body samples of tumor bearing mice using CR-39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University and thermal neutron facility of Paul Scherer Institute(PSI). We obtained NCAR images for mice injected intravenously by 10B-PEG liposome, 10B-transferrin-PEG liposome, or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha-track density measurements. In this study, we can increase the accumulation of 10B atoms in the tumor tissues by binding polyethylene-glycol chains to the surface of liposome, which increase the retention in the blood flow and escape the phagocytosis by reticulo-endothelial systems. Therefore, we will be able to apply NCAR technique for selection of effective 10B carrier in BNCT for cancer.

Animals↗
PubMed2004

[Six cases of thymic carcinoma: a clinical review].

Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated. We clinically review six patients with thymic carcinoma (three men and three women) who were admitted to our hospital from 1992 through 2002. Their ages ranged from 56 to 81 years (median 70.5). Four patients had chest pain, two were unable to swallow, and in one, who was asymptomatic, the tumor was detected by chance. Histologically, five cases were squamous cell carcinomas, and one was a lymphoepithelioma-like carcinoma. Four of the six patients had distant metastasis at diagnosis. Only one patient was able to undergo surgery, two received radiation therapy alone, and three were administered chemoradiation. The response to the chemoradiation was progression of the disease in two patients and no change in one. The response to radiation therapy was partial response in one patient and no change in one. In summary, chest pain is the most common symptom of thymic carcinoma. A symptomatic case suggests a poor prognosis resulting from the clinical behavior of thymic carcinoma, such as early distant metastasis or direct invasion of surrounding organs. Histologically, squamous cell carcinoma is the most common, and thymic carcinoma appears to be generally resistant to chemotherapy and radiotherapy.

Aged↗
PubMed2002

Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells.

We prepared tumor-specific immunoliposomes by coupling anti-BCG monoclonal antibodies to pH-sensitive fusogenic liposomes modified with succinylated polyglycidol (sucPG), in order to obtain efficient binding to, and endocytotic internalization into, the tumor cells. Mouse colon carcinoma 26 cells, which are known to share a common antigen with BCG, were used in in vitro experiments. BCG-sucPG immunoliposomes showed fusion ability under acidic conditions. Fluorescence microscopic observation indicated that BCG-sucPG immunoliposomes bound to colon 26 tumor cells and induced receptor-mediated endocytosis at 37 degrees C. Fusion assay by resonance energy transfer using N-(7-nitro-2-1,3-benzoxadiazol-4-yl) diacyl phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl) diacyl phosphatidylethanolamine suggested that fusion between BCG-sucPG immunoliposomes and endosomal and/or lysozomal membrane did occur. These results imply that the BCG-sucPG immunoliposomes transfer their content into the cytoplasm by fusing with the endosomal and/or lysozomal membrane after recognition of target cells and subsequent internalization into the cells by endocytosis.

Animals↗
PubMed2002

Effect of poly(ethylene glycol) grafts on temperature-sensitivity of thermosensitive polymer-modified liposomes.

A copolymer of N-isopropylacrylamide and N-acryloylpyrrolidine, which exhibits a lower critical solution temperature (LCST) at 38 degrees C, having a didodecyl group at the chain terminal was synthesized and calcein-loaded liposomes were prepared from a mixture of dioleoylphosphatidylethanolamine and the copolymer. While the contents release from the copolymer-modified liposomes was strongly accelerated around the LCST of the copolymer, some extent of the release was also observed below the LCST, probably because the partly-dehydrated copolymer chains interacted with the liposome membrane. When poly(ethylene glycol) with the number average molecular weight of 550 having a didodecyl group at the chain end was introduced into the copolymer-modified liposomes, the contents release from the copolymer-modified liposomes was effectively suppressed below the LCST but hardly affected above the LCST. As a result, the liposomes exhibited much sharper enhancement of the contents release in a narrow temperature region. The temperature-sensitive contents release property of the copolymer-modified liposomes became less significant in the presence of serum. However, inclusion of the anchor-bearing poly(ethylene glycol) derivative improved the contents release behavior of the copolymer-modified liposomes in the presence of serum.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Synthesis of novel cationic lipids having polyamidoamine dendrons and their transfection activity.

We designed a novel type of cationic lipid, lipids with a cationic polar group in the polyamidoamine dendron, because these dendron-bearing lipids are expected to form complexes with plasmid DNA and achieve efficient transfection of cells by synergy of endosome buffering and membrane fusion with the endosome, both of which are useful for the promotion of the transfer of plasmid DNA from endosome to cytosol. Four kinds of lipids with polyamidoamine dendrons of first to fourth generations, DL-G1, DL-G2, DL-G3, and DL-G4, were synthesized. The lipid with a dendron of a higher generation exhibited greater ability to form lipoplexes with plasmid DNA, as estimated by agarose gel electrophoresis. While the DL-G1 lipoplex did not transfect CV1 cells, the lipoplexes containing the DL-G2, DL-G3, or DL-G4 could induce transfection of the cells, and their activity was elevated with increasing generation of the dendron. Addition of dioleoylphosphatidylethanolamine (DOPE), which is known to increase fusion ability of a lipid membrane, into the lipoplexes greatly enhanced their transfection activity. In addition, the comparison with DC-Chol-containing lipoplex, which is widely used as a nonviral vector, showed that the DL-G3-DOPE lipoplex exhibits more efficient transfections. These findings imply that these dendron-bearing lipids may form the basis for a novel family of cationic lipids for efficient gene delivery.

Animals↗
PubMedDate not supplied

Temperature sensitization of liposomes by use of N-isopropylacrylamide copolymers with varying transition endotherms.

Three kinds of copolymers of N-isopropylacrylamide (NIPAM) with the same conformational transition temperature and varying transition endotherms were synthesized with N-acryloylpyrrolidine (APr), N,N-dimethylacrylamide (DMAM), and N-isopropylmethacrylamide (NIPMAM) as the comonomers. Two dodecyl groups were incorporated into the termini of these copolymers as an anchor for the fixation to a liposomal membrane. Egg yolk phosphatidylcholine liposomes having these copolymers were prepared and their temperature-sensitive contents release and association properties were investigated. While these copolymer exhibited a conformational transition at ca. 40 degrees C, DeltaH for the transition increased in the order of poly(APr-co-NIPAM) < poly(DMAM-co-NIPAM) < poly(NIPMAM-co-NIPAM). The liposomes containing poly(NIPMAM-co-NIPAM) showed a drastic release enhancement of entrapped calcein above the transition temperature, whereas the liposomes with poly(DMAM-co-NIPAM) and those with poly(APr-co-NIPAM) exhibited moderate and slight enhancement of calcein release above that temperature, respectively. On the contrary, the liposomes containing poly(APr-co-NIPAM) showed significant aggregation above the transition temperature, but the aggregation was hardly observed for the liposomes having poly(NIPMAM-co-NIPAM), indicating that poly(APr-co-NIPAM) more efficiently made the liposome surface hydrophobic. Thus, we concluded that the copolymer with a large DeltaH is suitable for obtaining functional liposomes with a temperature-sensitive contents release property, whereas the copolymer with a small DeltaH is appropriate for preparing functional liposomes with a temperature-sensitive surface property.

Acrylamides↗
PubMedDate not supplied

Transfection activity of polyamidoamine dendrimers having hydrophobic amino acid residues in the periphery.

We designed poly(amidoamine) dendrimers with phenylalanine or leucine residues at their chain ends. Thereby, we achieved efficient gene transfection of cells through synergy of the proton sponge effect, which is induced by the internal tertiary amines of the dendrimer, and hydrophobic interaction by the hydrophobic amino acid residues in the dendrimer periphery. Dendrimers having 16, 29, 46, and 64 terminal phenylalanine residues were prepared by the reaction of the amine-terminated poly(amidoamine) G4 dendrimer and L-phenylalanine using condensing reagent 1,3-dicyclohexylcarbodiimide. Transfection activity of these phenylalanine-modified dendrimers for CV1 cells, an African green monkey kidney cell line, increased concomitant with the increasing number of the terminal phenylalanine residues, except for the dendrimer with 64 phenylalanine residues, which showed poor water solubility and hardly formed a complex with DNA at neutral pH. However, under weakly acidic conditions, the dendrimer with 64 phenylalanine residues formed a complex with DNA, thereby achieving highly efficient transfection. In contrast, the attachment of L-leucine residues was unable to improve the transfection activity of the parent dendrimer, probably because of the relatively lower hydrophobicity of this amino acid. The phenylalanine-modified dendrimer exhibited a higher transfection activity and a lower cytotoxicity than some widely used transfection reagents. For that reason, the phenylalanine-modified dendrimers are considered to be promising gene carriers.

Amino Acids↗
PubMedDate not supplied

Temperature sensitization of liposomes by use of thermosensitive block copolymers synthesized by living cationic polymerization: effect of copolymer chain length.

We prepared block copolymers of (2-ethoxy)ethoxyethyl vinyl ether (EOEOVE) and octadecyl vinyl ether (ODVE) with the number average molecular weights of 6900, 9300, and 16 700 by living cationic polymerization. The poly(EOEOVE) block acts as a temperature-sensitive moiety, and the poly(ODVE) block acts as an anchor moiety. We also investigated the effect of chain length of the copolymer poly(EOEOVE) block on the ability to sensitize liposomes. The copolymers underwent a coil-globule transition at approximately 36 degrees C in the presence of a membrane of egg yolk phosphatidylcholine (EYPC), detected using differential scanning calorimetry (DSC). Liposomes encapsulating calcein, a water-soluble fluorescent dye, were prepared from mixtures of dioleoylphosphatidylethanolamine, EYPC, and the copolymers. While the copolymer-modified liposomes released little calcein below 30 degrees C, release was enhanced above 35 degrees C, indicating that dehydrated copolymer chains destabilized the liposome membrane. In addition, copolymers with a longer poly(EOEOVE) block induced a more drastic enhancement of contents release in a narrow temperature region near the transition temperature of the poly(EOEOVE) block. As a result, the copolymer with an average molecular weight of 16 700 generated highly sensitive liposomes that produced rapid and dramatic release of the contents in response to temperature.

Ethers↗
PubMedDate not supplied

Preparation of efficient gene carriers using a polyamidoamine dendron-bearing lipid: improvement of serum resistance.

In a previous study, we developed a novel cationic lipid consisting of polyamidoamine dendron of third generation and two dodecyl chains, designated as DL-G3, which in combination with a fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) achieves efficient transfection of CV1 cells by synergetic action of the proton sponge effect and membrane fusion. This study examines the effect of serum on the transfection activity of the DL-G3-DOPE-plasmid DNA lipoplexes. The transfection activity of a lipoplex with a composition optimized in the absence of serum decreased markedly in the presence of serum. However, the lipoplexes that induce efficient transfection in the presence of serum were obtainable by controlling the charge ratio of the primary amine of the DL-G3 to the phosphate group (N/P ratio) and DOPE content. The complex, which exhibited the highest transfection activity in the presence of serum, has a lower N/P ratio and higher DOPE content than that optimized in the absence of serum. Whereas disintegration of these complexes was induced by addition of heparin, which is a polysaccharide with negatively charged groups, the complex that retained transfection activity in the presence of serum required more negative charges of heparin for complex disintegration. That result implies its higher stability against negatively charged serum proteins. Comparison of the serum-resistant complex with some commercially available transfection reagents, such as Lipofectamine and SuperFect, indicates that the DL-G3 complex achieved more efficient transfection of these cells in the presence of serum.

Amination↗
PubMedDate not supplied

Acceleration of enzymatic reaction of trypsin through the formation of water-soluble complexes with poly(ethylene glycol)-block-poly(alpha,beta-aspartic acid).

The amidase activity of bovine pancreas trypsin in water-soluble complexes with poly(ethylene glycol)-block-poly(alpha,beta-aspartic acid) (PEG-PAA) was evaluated by a colorimetric assay using L-lysine p-nitroanilide as a substrate. The enzymatic reaction of trypsin was accelerated through the complexation with PEG-PAA. By determining the kinetic parameters of the enzymatic reaction of trypsin, it was confirmed that the catalytic rate constant of the complexed trypsin was 15 times higher than that of the native trypsin. From the evaluation of pH dependence of initial reaction rate, it was indicated that this acceleration was induced by a stabilization of the imidazolium ion of the His residue in the catalytic site, the Asp-His-Ser triad, of trypsin due to the Asp units of PEG-PAA. The hydrogen bonded Asp-His pairs are critical constituents in several key enzymatic reactions including serine protease and apurinic endonucleases, and it was expected that the acceleration of the catalytic reaction might occur for other enzymes by the formation of water-soluble complexes with PEG-PAA.

Amino Acids↗