Biomedical subjects

S Kumazawa

Publications and source records attributed to S Kumazawa.

At least 19 recordsLinked to original sources

PubMed2001

Direct observation of deuterium migration in crystalline-state reaction by single-crystal neutron diffraction. III. Photoracemization of 1-cyanoethyl cobaloxime complexes.

The H atoms bonded to the chiral C atoms (stereogenic center) of the 1-cyanoethyl groups in two cobalt complexes, [(R)-1-cyanoethyl]bis(dimethylglyoximato)(pyridine)cobalt(III) (2) and [(R,S)-1-cyanoethyl]bis(dimethylglyoximato)(piperidine)cobalt(III) (3), were replaced with D atoms, such as Co--C*D(CH(3))CN. The crystals of the two cobalt complexes were irradiated with a xenon lamp for 72 h and 27 d, respectively. The unit-cell dimensions were gradually changed with retention of the single-crystal form. The crystal structures after irradiation were determined by neutron diffraction. In each crystal the chiral 1-cyanoethyl group of one of the two crystallographically independent molecules was partly inverted to the opposite configuration, whereas that of the other molecule kept the original configuration. The C*--D bond in the inverted group was completely conserved in the process of the inversion of the chiral alkyl group. This suggests that the inversion of the chiral 1-cyanoethyl group proceeds with the rotation of the cyanoethyl radical after the Co--C bond cleavage by photo-irradiation so that the opposite side of the radical faces the Co atom. This is followed by recombination of the Co--C bond to form the inverted 1-cyanoethyl group.

Journal Article↗

PubMed2001

Role of lipophilicity and hydrogen peroxide formation in the cytotoxicity of flavonols.

We compared the lipophilicity and toxicity of the four flavonols, galangin, kaempferol, quercetin and myricetin, which respectively have no, one, two and three hydroxyl groups on the B-ring. The lipophilicity was in the order of myricetin < quercetin < kaempferol < galangin. The cytotoxicity determined by a colony-formation assay with Chinese hamster lung fibroblast V79 cells was in the order of quercetin < kaempferol < galangin < myricetin. Apart from myricetin, the order of lipophilicity was the same as that of cytotoxicity, implying that the cytotoxicity was attributable to the lipophilicity. The cytotoxicity of myricetin was attributable to the hydrogen peroxide formed by autoxidation.

Animals↗

PubMed2001

Steric effects on interaction of tea catechins with lipid bilayers.

Interaction of tea catechins with lipid bilayers has been investigated with liposome systems. Tea catechins are classified into cis-type and trans-type from the configuration of the two hydrogens at the 2 and 3 positions on the C-ring. The amount of trans-type catechins incorporated into liposomes was less than that of the respective cis-type catechins. Furthermore, the order of the partition coefficients of catechins in an n-octanol/PBS system is the same as that of the amount incorporated into liposomes. These results indicate that in addition to the number of hydroxyl groups on the B-ring and the presence of the galloyl moiety, the stereochemical structure of the C-ring also governs the hydrophobicity and the affinity for lipid bilayers. Trans-type catechins with the galloyl moiety were located on the surface of the lipid bilayer, as well as cis-type catechins with the galloyl moiety, and perturbed the membrane structure. These different stereochemical structures should influence the affinity for lipid bilayers, the alteration of membrane structures, and the difference in the order of the biological activities.

Catechin↗

PubMed2001

Immunochemical detection of a lipofuscin-like fluorophore derived from malondialdehyde and lysine.

The accumulation of fluorescent age pigment or lipofuscin is a frequently observed age-associated cellular alteration in a variety of postmitotic cells of many species. These pigments are observed within granules composed, in part, of damaged protein and lipid. Modification of various biomolecules by aldehyde products of lipid peroxidation is believed to contribute to lipofuscin and ceroid formation. In the present study, we raised a monoclonal antibody (MAb 1F83) directed to the malondialdehyde-modified protein and identified a lipofuscin-like dihydropyridine fluorophore as the major epitope. This antibody was used to conclusively demonstrate that the fluorophore forms on oxidatively modified low density lipoproteins. In addition, we demonstrated that the materials immunoreactive to MAb 1F83 indeed constituted the atherosclerotic lesions, in which intense positivity was associated primarily with macrophage-derived foam cells. The results of this study suggest that the reaction between the lipid peroxidation-derived aldehyde and primary amino groups of protein might represent a process common to the formation of the lipofuscin-like fluorophore during aging and its related diseases.

Animals↗

PubMed2000

Affinity of polyphenols for lipid bilayers.

Interaction of tea catechins with lipid bilayers has been investigated with liposome systems. Epicatechin gallate had the highest affinity for lipid bilayers, followed by epigallocatechin gallate, epicatechin, and epigallocatechin. Epicatechin gallate and epigallocatechin gallate in the surface of lipid bilayer perturbed the membrane structure.

Animals↗

PubMed2000

Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats.

Eriocitrin, a flavonoid glycoside present in lemon fruit, is metabolized in vivo to a series of eriodictyol, methylated eriodictyol, 3,4-dihydroxyhydrocinnamic acid, and their conjugates. Plasma antioxidant activity increased following oral administration of aqueous eriocitrin solutions to rats. Eriocitrin metabolites were found in plasma and renal excreted urine through HPLC and LC-MS analyses. Eriocitrin was not detected in plasma and urine, but eriodictyol, homoeriodictyol, and hesperetin in their conjugated forms were detected in plasma of 4.0 h following administration of eriocitrin. In urine for 24 h, both nonconjugates and conjugates of these metabolites were detected. 3,4-Dihydroxyhydrocinnamic acid, which is metabolized from eriodictyol by intestinal bacteria, was detected in slight amounts with each form in 4.0-h plasma and 24-h urine. Eriocitrin was suggested to be metabolized by intestinal bacteria, and then eriodictyol and 3,4-dihydroxyhydrocinnamic of its metabolite were absorbed. Following administration of eriocitrin, plasma exhibited an elevated resistance effect to lipid peroxidation. Eriocitrin metabolites functioning as antioxidant agents are discussed.

Animals↗

PubMed2000

Apoptosis-inducing activity of galloyl monosaccharides in human histiocytic lymphoma U937 cells.

Three galloyl monosaccharides contained in medicinal plants were examined for apoptosis-inducing activity in human histiocytic lymphoma U937 cells. Tetragalloyl glucose (TgG) induced apoptosis as found by chromatin condensation, DNA ladder formation, and inhibition by a caspase inhibitor. Digalloyl hamamelose had moderate activity, while monogalloyl glucose was only marginally active. These findings suggest that the number and disposition of their phenolic groups are important for apoptosis induction. TgG induced apoptosis in human colon and stomach cancer cell lines as well, indicating it is potentially useful as an anti-cancer agent.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Direct observation of deuterium migration in crystalline-state reaction by single-crystal neutron diffraction. II. 3-1 photoisomerization of a cobal-oxime complex

Single crystal neutron diffraction analysis of photo-exposed (3-cyanopropyl-d2(alpha,alpha))-[(R)-1-phenylethylamine-d11]bis(dimethylglyoximato-d14)cobalt(III) was carried out in order to clarify the mechanism of the crystalline-state photoisomerization of the 3-cyanopropyl group bonded to the Co atom in some cobaloxime complexes. Before irradiation the two H atoms bonded to the C1 atom of the 3-cyanopropyl group were exchanged with the D atoms such as --CH2CH2CD2CN. On exposure to a xenon lamp, the cell dimensions of the crystal were gradually changed. After 7 d exposure the change became insignificantly small. The structure was analyzed by neutron diffraction. The 3-cyanopropyl group was transformed to the 1-cyanopropyl group such as --CD(CN)C(H1/2,D1/2)2CH3 with retention of the single-crystal form. This indicates that one of the D atoms bonded to C1 migrates to either position bonded to C2. The other atoms of the complex remained unchanged. These results indicate that photoisomerization proceeded in two steps: the 3-cyanopropyl group was isomerized to the 2-cyanopropyl group in the first place and then the 2-cyanopropyl group was transformed to the 1-cyanopropyl group. Moreover, it was made clear that the second-step isomerization was irreversible, since one of the D atoms was retained. The disordered structure at C2 is estimated to be caused by the interconversion between the 1-cyanopropyl group produced and its dehydrogenated olefin after the photoisomerization.

Journal Article↗

PubMed1999

Interaction of tea catechins with lipid bilayers investigated with liposome systems.

Interaction of tea catechins with lipid bilayers was investigated with liposome systems, which enabled us to separate liposomes from the external medium by centrifugation. We found that epicatechin gallate had the highest affinity for lipid bilayers, followed by epigallocatechin gallate, epicatechin, and epigallocatechin. Epicatechin gallate and epigallocatechin gallate in the surface of lipid bilayer perturbed the membrane structure.

Catechin↗

PubMed1996

Sustained release of adriamycin from implanted hydroxyapatite blocks for the treatment of experimental osteogenic sarcoma in mice.

A sustained-release drug delivery system was developed using a hydroxyapatite (HA) block loaded with adriamycin (ADR) by cenrifugation. Release of ADR was sustained for 66 days in vitro and for 4 weeks in vivo following intramuscular implantation in mice. ADR concentrations in plasma, liver, and kidney were from 0.25% to 10% of that at the implantation site. ADR-HA blocks implanted into osteogenic sarcomas in mice markedly inhibited tumor growth. This drug delivery system provides sustained release of the cancer chemotherapeutic agent and may prove useful for treating malignant tumours while minimising systemic side effects.

Animals↗

PubMed1995

A novel drug delivery system for osteomyelitis using porous hydroxyapatite blocks loaded by centrifugation.

A novel drug delivery system for osteomyelitis was developed using porous hydroxyapatite blocks (HA-b) loaded with antibiotics by centrifugation. In the study, 10 mm3 HA-b was placed in a container and mixed with antibiotic solution; the antibiotic was then loaded into the pores of the HA-b by centrifuging at 1500 rpm for 15 min. Slow release of HA-b in both moist form and dried form (by heating at 160 degrees C) was tested after loading with the antibiotic arbekacin sulfate (ABK), 1-N-(S)-4 amino-2-hydroxybutyryl dibekacin. To estimate the concentration of antibiotic, both forms of HA-b were placed in 3 mL of phosphate buffered saline (PBS), which was replaced every 48 h. In both groups, which were loaded with 70 mg ABK per one block of HA (concn 0.5 microgram/mL) which is sufficiently high to control most pathogens, was maintained for 21 exchanges of PBS (after 42 days). Minimum inhibitory concentration for methicillin-resistant Staphylococcus aureus (MRSA), 3.13 micrograms/mL, was maintained until nine exchanges took place (after 18 days). The centrifugation method is simple, and dried ABK produced by heating loaded HA-b is particularly useful in clinical applications for osteomyelitis.

Anti-Bacterial Agents↗

PubMed1994

Treatment of osteomyelitis by antibiotic impregnated porous hydroxyapatite block.

A novel drug delivery system was developed for osteomyelitis using porous hydroxyapatite blocks (HA-b) that were impregnated with antibiotics by a centrifuge method. For the experimental study, a 10 mm3 HA-b was placed in a container, mixed with an antibiotic solution and centrifuged at 1500 rpm for 15 min for the purpose of impregnating antibiotics into the pores. The slow release activity of antibiotic (Arbekacin sulfate [1-N-(S)-4 amino-2-hydroxybutyryl dibekacin]) from the HA-b was tested. An evaluation was made of the slow-releasing capabilities of the ABK from HA-b which was still maintained at 0.5 microgram/ml within 21 exchanges of PBS after 42 days. Consequently, seven patients with osteomyelitis, including one with tuberculosis and two with infected hip arthroplasty, have been treated. On a follow-up study, all of the foci had completely healed by the end of the follow-up period without complications. This new method is simple and can be performed safety as a one-stage operation.

Adolescent↗

PubMed1994

Nuclear magnetic resonance study and secondary structure determination of the antibiotic peptide, aibellin.

Aibellin is a 20-residue peptide antibiotic that has been isolated from the fungus Verticimonosporium ellipticum. Sequence-specific assignment of the 1H- and 13C-NMR signals of aibellin in a methanol solution was achieved by using the two-dimensional NMR technique. Furthermore, its secondary structure was characterized by circular dichroism (CD) and NOESY spectra. The observed NOEs, 3JNHC alpha H coupling constants and amide hydrogen-deuterium (H-D) exchange rates show that the peptide consisted of two alpha-helices and a bent structure around a Pro-14 residue.

Amino Acid Sequence↗

PubMed1994

A new model of shouldered survival curves.

Recently, the linear-quadratic equation has been used to construct the dose-response relationships of ionizing radiation. The radiobiological theory on which this relationship is based indicates that at low doses, the risk of a biological lesion being formed should depend linearly on dose if a single event is required or quadratically on dose if two events are required. The same approach has also been used to construct the shouldered survival curves, which indicate a lower response of cell killing at low doses of low linear energy transfer (LET) radiation than at high doses because of repair. However, a different approach is possible, derived from the concept of generating the hybrid lognormal distribution, in which the hybrid form of linear and logarithmic components of a random variable is used. The hybrid form is a formulation of the phenomenon in which there is a feedback mechanism against the large change in the random variable. This paper presents a new model of shouldered survival curves, called a hybrid scale model, which has two parameters: the inactivation constant and the protective factor. In the model, the surviving fraction, normalized by a protective factor plotted in a hybrid scale, is assumed to be linear against the dose. This simple model provides an implication of the shoulder of survival curve and the effect of recovery time of radiation damage, as well as giving a good to the well-known data of split-dose experiments with mammalian cells.

Animals↗

PubMed1994

Effect of aibellin, a peptide antibiotic, on propionate production in the rumen of goats.

Aibellin was administered in feed to goats (16 to 18 kg of BW) for 12 d. At 80 mg/d, the molar percentage of propionate in rumen fluid increased significantly in 8 d, and the effect lasted for as long as 10 d after administration ceased. Total VFA concentration, protozoa numbers, and NDF digestibility were not depressed significantly at this dosage but were reduced at 100 mg/d with little further increase in the molar percentage of propionate. Therefore, the optimal dosage of aibellin was 80 mg/d under our experimental conditions. In contrast, monensin (30 mg/d) and gramicidin D (60 mg/d) decreased total VFA concentration and protozoa numbers when supplemented to obtain molar percentages of propionate comparable to 80 mg/d of aibellin. From these results, aibellin may be easier and safer to use than monensin and gramicidin D to modify rumen fermentation.

Animals↗

PubMed1994

Structural elucidation of aibellin, a new peptide antibiotic with efficiency enhancing activity on rumen fermentation.

A new peptide antibiotic, aibellin, that had the efficiency enhancing activity on rumen fermentation, was isolated from the culture broth of the fungus, Verticimonosporium ellipticum D1528, and its primary structure was elucidated from spectrometric analysis and chemical degradation. Aibellin is a 20-residue peptaibol, and it has a unique structural feature in the novel C-terminal amino alcohol. Moreover, aibellin is the first peptaibol that possesses two acidic amino acids in the C-terminal region and a Phe residue in the middle of the sequence.

Amino Acid Sequence↗

PubMed1994

Structural studies of new macrolide antibiotics, shurimycins A and B.

The structures of new antibiotics, shurimycins A and B produced by Streptomyces hygroscopicus A1491, were elucidated from the physico-chemical properties, 2D NMR techniques and chemical degradation experiments to be 36-membered macrolides related to azalomycins, scopafungin and guanidylfungins. Shurimycins were active against fungi and Gram-positive bacteria.

Anti-Bacterial Agents↗

PubMed1993

Cell-mediated immune-pancytopenia complicating primary Sjögren's syndrome.

A 64-year-old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS-A, and SS-B. Impaired cell-mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjögren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjögren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors.

Blood Physiological Phenomena↗