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Biomedical subjects

T Katsu

Publications and source records attributed to T Katsu.

At least 19 recordsLinked to original sources
PubMed2005

Proline residue-modified polycationic analogs of gramicidin S with high antibacterial activity against both Gram-positive and Gram-negative bacteria and low hemolytic activity.

Novel polycationic analogs of the cyclic decapeptide antibiotic, gramicidin S, possessing NH(2), D/L-Phe-NH or L-Lys-NH groups at the 4alpha- or 4beta-positions of the L-Pro residues, were synthesized. While L-Pro(4alpha/beta-NH(2))-containing analogs exhibited much weaker antibacterial activity, the D/L-Phe and L-Lys-substituted analogs exhibited higher antibacterial activity against Gram-negative bacteria than the parent gramicidin S. All of these additional amino group-containing analogs showed substantially reduced toxicity against human blood cells.

Amination↗
PubMed2003

Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis.

Susceptibility to drug dependence and drug-induced psychoses is influenced not only by the pharmacological effects of the drug but also by the genetic factors of the individual. To clarify the latter, we investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene (SLC6A3) encoding the dopamine transporter, which is the primary site of METH activity in the brain. Four exonic polymorphisms of the hDAT1 gene, 242C/T (exon 2), 1342A/G (exon 9), 2319G/A (3'UTR), and VNTR (3'UTR) were examined. Although there was no significant difference in genotypic and allelic distribution of the four polymorphisms between all METH dependence/psychosis patients (N=124) and controls (N=160), the patients with METH psychosis lasting for 1 month or more after discontinuance of METH consumption showed a significant excess of nine- or fewer repeat alleles of the VNTR in 3'UTR of the hDAT1 gene (P=0.0054, OR=4.24, 95% CI=2.46-7.31). The present study demonstrated that the presence of nine- or fewer repeat alleles of hDAT1 is a strong risk factor for a worse prognosis of METH psychosis.

Adult↗
PubMed2001

Ion-selective electrode for transmembrane pH difference measurements.

A triethylammonium-sensitive electrode was constructed using sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate as an ion-exchanger and benzyl 2-nitrophenyl ether as a solvent mediator in a poly(vinylchloride) membrane matrix and was used to determine the pH difference across a cell membrane. The method is based on monitoring of the pH gradient-induced uptake of triethylammonium in situ. The triethylammonium electrode exhibited a near-Nernstian response to triethylammonium in the concentration range of 5 x 10(-6)-1 x 10(-2) M with a slope of 58.5 mV per concentration decade in a buffer solution composed of 150 mM NaCl and 10 mM NaH2PO4/Na2HPO4 (pH 7.5). The limit of detection was 1 microM. In experiments using liposomes, the uptake of triethylammonium into liposomes was quantitatively induced according to the pH difference across the liposomal membrane. The transmembrane pH differences in Escherichia coli cells and the light-induced pH differences across the envelope vesicles of Halobacterium halobium were successfully determined by the present method.

Cell Membrane↗
PubMed2001

Discrimination of methylammonium from organic ammonium ions using ion-selective electrodes based on calix[4]arene-crown-6 conjugates.

Calix[4]-bis-2,3-naphtho-crown-6 can be used to discriminate between methylammonium and other organic ammonium ions. An electrode based on this ionophore, potassium tetrakis(p-chlorophenyl)borate (20 mol% relative to the ionophore) as an ionic additive and bis(2-ethylhexyl) sebacate as a solvent mediator in a poly(vinyl chloride) membrane matrix, displayed higher selectivity for methylammonium than for various other organic ammonium ions. However, there was considerable interference by inorganic cations, especially Cs+. Similar calix[4]arene-crown-6 conjugates, such as calix[4]-bis-1,2-benzo-crown-6, calix[4]-bis-crown-6, 1,3-dioctyloxy-calix[4]arene-crown-6, 1,3-diisopropoxy-calix[4]arene-crown-6 and 1,3-dimethoxy-calix[4]arene-crown-6 were less effective in discriminating methylammonium.

Journal Article↗
PubMed2001

Acyclic neutral carrier-based polymer membrane electrode for a stimulant, phentermine.

Groups of dioxadicarboxylic diamides, which were developed as potential ionophores for inorganic cations, were found to act as ionophores for a stimulant, phentermine. Especially, N,N-dioctadecyl-N',N'-dipropyl-3,6-dioxaoctanediamide, which was originally developed as a lead ionophore and is commercially available from Fluka as lead ionophore I, was suitable for making a phentermine-selective electrode. The electrode constructed using this ionophore and bis(2-ethylhexyl) sebacate as a solvent mediator in a poly(vinyl chloride) membrane matrix discriminated between phentermine and analogous compounds more effectively than an electrode based on dibenzo-18-crown-6, a representative ionophore for organic ammonium ions. Moreover, the present electrode showed remarkably little interference by inorganic cations, such as Na+ and K+, as well as lipophilic quaternary ammonium ions including (C2H5)4N+ and (C3H7)4N+. The electrode exhibited a near-Nernstian response to phentermine in the concentration range of 2 x 10(-6) to 1 x 10(-2) M with a slope of 54.8 mV per concentration decade in 0.1 M MgCl2. The lower limit of detection was 7 x 10(-7) M. This electrode was applied to determine phentermine in a cationic-exchange resin complex of this stimulant, which is the general dosage form in medical use.

Journal Article↗
PubMed2001

[A case of spinocerebellar ataxia type 6 with hypochondriasis and severe parkinsonism].

We report a case of 68-year-old woman who was diagnosed spinocerebellar ataxia type 6 (SCA 6) by genomic testing. She presented hypochondriasis, parkinsonism, and ataxia. Since the age of 60, she noted difficulty in walking due to dizziness, and MRI showed minimal cerebellar atrophy. She became unable to walk without assistance at the age 67. She was referred to us when she was 68 years old. She had no family history of cerebellar ataxia, and her general physical examination was normal. Her speech was fluent, with neither slurring nor scanning, and she complained of much anxiety regarding her physical condition and was diagnosed as having hypochondriasis. Neurological examination revealed parkinsonism consisting of small steppage gait, mask-like face, akinesia, rigidity of neck and limbs, and postural instability. She also showed cerebellar signs such as saccadic smooth pursuit, ataxia of upper and lower limbs, and increased tendon reflexes. Her parkinsonism had developed slowly and symmetrically yet she showed a lack of response to levodopa. Our results suggest that the genomic testing is useful for differential diagnosis for the diseases presenting ataxia and parkinsonism, even if the family history is negative.

Aged↗
PubMed1999

Mexiletine-sensitive membrane electrode for medical application.

Response characteristics of mexiletine-sensitive membrane electrodes based on crown ether and ion-exchanger were examined in a physiological saline in order to find an electrode suitable for determining concentrations of this drug under physiological conditions. Among various crown ethers screened, 4',4"(5")-di-tert-butyldicyclohexano-18-crown6 showed the highest sensitivity to mexiletine in physiological saline containing 0.15 M NaCl and 5 mM 4-(2-hydroxyethyl)-2-piperazineethanesulfonic acid (Hepes) NaOH (pH 7.4). However, the detection limit of 30 microM was 10 times higher than that of 3 microM observed with the electrode based on an ion-exchanger, sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate. Having high selectivity against inorganic cations such as Na+ or K+, the electrode using the ion-exchanger enabled us to determine the level of mexiletine in saliva, the monitoring of which is quite effective for controlling the dose of this drug noninvasively. The mexiletine concentrations determined with the mexiletine electrode compared favourably with those determined by high-performance liquid chromatography which requires an additional procedure to extract mexiletine from saliva.

Anti-Arrhythmia Agents↗
PubMed1999

Application of calcein-loaded liposomes for the determination of membrane channel size.

We found that calcein-loaded liposomes can be used to evaluate the sizes of channels in membranes by measuring changes in calcein release when the molecular size of the solute added to the outer suspension medium is changed. If the solute added to the outer medium can enter the inner aqueous phase through the channel, the osmotic pressure of the inner phase increases, causing bursting of the liposomes and the release of calcein. Thus, the size of the channel formed in the liposomal membrane can be determined by examining whether the solute added to the outer medium induces calcein release. We used a series of sugars as solutes and estimated the channel size formed by polyene antibiotics. The results agreed well with those conducted in a similar manner using erythrocytes, demonstrating that this method should be useful for examining channel sizes in membranes.

Carbohydrates↗
PubMed1998

Determination of the pH difference across a cell membrane using a methylammonium-selective membrane electrode.

A method was developed for determining pH differences across cell membranes using a methylammonium-selective membrane electrode, based on monitoring of the pH gradient-induced uptake of methylammonium in situ. The methylammonium electrode was constructed using calix[6]arene-hexaacetic acid hexaethyl ester as a neutral carrier and bis(2-ethylhexyl) sebacate as a membrane solvent in a poly(vinyl chloride) membrane matrix. This electrode exhibited a near-Nernstian response to methylammonium in the concentration range 2 x 10(-5)-1 x 10(-2) M with a slope of 58 mV per concentration decade in a buffer solution of 150 mM choline chloride-10 mM TRIS-HCl (pH 7.5). The limit of detection was 5 x 10(-6) M. In experiments using liposomes, the uptake of methylammonium into liposomes occurred effectively when the pH of the outside suspension medium was alkaline, and the determination of changes in methylammonium concentrations in the outer medium was quantitatively related to changes in the pH differences across the liposomal membrane. The transmembrane pH differences in Escherichia coli cells were also determined by this method.

Cell Membrane↗
PubMed1997

Potentiometric flow injection determination of serum bromide in patients with epilepsy.

A flow injection system was constructed using a bromide-selective electrode and used to determine serum bromide in patients with epilepsy. A 10-microliter serum sample was injected into a carrier stream flowing at 0.12 ml min-1. Potential changes and bromide concentrations were linearly related in the range 3-50 mM. The lower limit of detection for serum bromide was 1 mM and this electrode sensitivity spanned the entire concentration range required for bromide therapy (9-24 mM). The results compared favourably with those obtained by colorimetry.

Autoanalysis↗
PubMed1997

Purification and characterization of a hemolysin produced by Vibrio mimicus.

Vibrio mimicus is a causative agent of human gastroenteritis. This pathogen secretes a pore-forming toxin, V. mimicus hemolysin (VMH), which causes hemolysis by three sequential steps: binding to an erythrocyte membrane, formation of a transmembrane pore, and disruption of the cell membrane. VMH with a molecular mass of 63 kDa was purified by ammonium sulfate precipitation and column chromatography with phenyl Sepharose HP and Superose 6 HR. The hemolytic reaction induced by VMH continued up to disruption of all erythrocytes in the assay system. Moreover, VMH that bound preliminarily to erythrocyte ghosts showed a sufficient ability to attack intact erythrocytes. These results suggest reversible binding of the toxin molecule to the membrane. The final cell-disrupting stage was effectively inhibited by various divalent cations. Additionally, some cations, such as Zn2+ and Cu2+, blocked the pore-forming stage at high concentrations. Although VMH could disrupt all kinds of mammalian erythrocytes tested, those from horses were most sensitive to the hemolysin. Horse erythrocytes were found to have the most toxin-binding sites and to be hemolyzed by the least amount of membrane-bound toxin molecules, suggesting that toxin binding to and pore formation on erythrocytes are more effective in horses than in other mammals. Purified VMH induced fluid accumulation in a ligated rabbit ileal loop in a dose-dependent manner. In addition, the antibody against the hemolysin obviously reduced enteropathogenicity of living V. mimicus cells. These findings clearly demonstrate that VMH is probably involved in the virulence of this human pathogen.

Ammonium Sulfate↗
PubMed1994

Structure-function relationships of tachyplesins and their analogues.

Haemocytes of the horseshoe crab (Limulus) contain a new family of arthropodous peptide antibiotics, termed the tachyplesin family. These cationic peptides are composed of 17-18 amino acid residues with a C-terminal arginine alpha-amide. Tachyplesin I takes on a fairly rigid conformation constrained by two disulphide bridges and adopts a conformation consisting of an antiparallel beta-sheet connected by a beta-turn. Isopeptides of tachyplesin I with amino acid replacements, tachyplesins II and III, and polyphemusins I and II have also been found in the haemocytes of the South-East Asian species and Limulus polyphemus. These peptides are present in abundance in the small granules of the haemocytes and inhibit strongly the growth of not only Gram-negative and Gram-positive bacteria but also fungi such as Candida albicans. Tachyplesin exists in the prepro form consisting of 77 residues; this precursor is probably processed by intracellular proteases and an amidation enzyme before incorporation into the small granules of the haemocytes. We examined the mode of action of tachyplesin I on biomembranes, comparing it with that of gramicidin S. Tachyplesin caused an efflux of K+ from Staphylococcus aureus and Escherichia coli cells similar to that caused by gramicidin S. Another antimicrobial substance, anti-LPS factor, has been isolated from haemocytes.

Amino Acid Sequence↗
PubMed1993

Mode of action of an antimicrobial peptide, tachyplesin I, on biomembranes.

An antimicrobial peptide, tachyplesin I, isolated from hemocytes of the horseshoe crab, Tachypleus tridentatus, increased the K+ permeability of Staphylococcus aureus and Escherichia coli cells, concomitantly reducing cell viability. At a higher concentration range, this peptide also enhanced the permeability of human erythrocytes. Tachyplesin decreased the phase transition temperature of an artificial membrane composed of dipalmitoylphosphatidylglycerol and, further, broadened it extensively, while it did not affect that of dipalmitoylphosphatidylcholine membrane. The latter result related closely to the fact that this peptide acted weakly on erythrocytes in which acidic lipids constitute a minor portion. Tachyplesin altered the normal discoid shape of human erythrocytes to a crenated form, suggesting that the peptide accumulated predominantly in the outer half of the membrane bilayer and destabilized the membrane structure, thus causing the change in permeability. The mode of action of tachyplesin was compared with that of gramicidin S, a peptide forming an amphiphilic structure analogous to tachyplesin.

Amino Acid Sequence↗
PubMed1992

Improvement of reconstitution of the Cl(-)-translocating ATPase isolated from Acetabularia acetabulum into liposomes and several anion pump characteristics.

The improved reconstitution of the Mono Q-III fraction, a Cl(-)-translocating ATPase, isolated from Acetabularia acetabulum (Ikeda et al. (1990) Biochemistry 29, 2057-2065) into liposomes rendered transport properties of this enzyme clear. The liposomes were prepared by the reversed-phase method using egg lecithin and cholesterol in a molar ratio of 2:1 and the purified ATPase was incorporated into the liposomes by a dialysis for 3 h. About 80% of the ATPase was incorporated into the liposomes. The weight ratio of the enzyme to lipid was 1:400-600. A sigmoid curve was obtained when the Cl(-)-transport activity of the enzyme was plotted against Cl- concentration. Hill's plot afforded a half-substrate concentration [S]0.5 of 45 mM and a Hill's coefficient n of 2.33. Effects of Br- and F- on the Cl(-)-transport were also examined in the reconstituted system, both halide ions decreased the 36Cl- efflux significantly. These kinetic data are in good agreement with the electrophysiological data presented by Tittor et al. ((1983) J. Membr. Biol. 75, 129-139).

Acetabularia↗
PubMed1991

Amphiphile-induced erythrocyte shape change and simultaneous tetraethylammonium ion uptake.

Amphiphile-induced tetraethylammonium ion (TEA+) uptake into human erythrocytes was examined along with cell shape change. A TEA(+)-sensitive electrode was used to determine the amount of uptake. TEA+ was preferentially incorporated into erythrocytes when amphiphiles changed cell shape to an invaginated form. This was contrasted with the release of acetylcholinesterase outside cells which occurred markedly with the amphiphiles, causing the crenated form. It was suggested that the invagination of erythrocyte membrane stimulated the formation of vacuoles, in which TEA+ existing in an external medium was entrapped.

Erythrocyte Deformability↗
PubMed1991

New agents to increase the permeability of the outer membrane of Escherichia coli.

Two diamines were prepared to investigate the structure-activity relationship required for an increase in the permeability of the outer membrane of Escherichia coli. It was found that diamine (a), bis[4-(2-methylaminoethoxy)phenyl]methane dihydrochloride, increased the permeability of the membrane, while diamine (b), 1,4-bis(2-methylaminoethoxy)benzene dihydrochloride, did not. The result indicated that the existence of bulky hydrophobic moiety is important to cause an increase in the permeability.

Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone↗