Hidetoshi Kutsuki

High-yield Production of Optically Active 1, 2-Diols from the Corresponding Racemates by Microbial Stereoinversion

A novel method for producing optically active 1,2-diols by microbial Stereoinversion was developed. It was found that some microorganisms could convert only (R)-1,2-pentanediol in the racemate to the (S)-enantiomer. Candida parapsilosis produced 27.9 g/l of (S)-1,2-pentanediol from 30 g/l of the racemate in 24 hr of reaction (molar yield 93%, enantiomeric excess 100%). This Stereoinversion proceeded via oxidation of (R)-1,2-pentanediol to 1-hydroxy-2-pentanone by an NAD+-linked (R)-specific alcohol dehydrogenase and reduction of 1-hydroxy-2-pentanone to (S)-1,2-pentanediol by an NADPH-linked (S)-specific 2-keto-1-alcohol reductase. This microbial stereo-inversion was applicable to ten 1,2-diols. Optically active 1,2-diols prepared by the reaction had the same configuration at the chiral center.

Blood Purification Therapies Using Dextran Sulfate Cellulose Columns Liposorber and Selesorb

Abstract:  Liposorber is a column used for plasma purification that adsorbs low‐density lipoproteins with high selectivity, while Selesorb is a column that selectively adsorbs anti‐DNA antibodies, anticardiolipin antibodies, and immune complexes. Both columns are packed with carriers, where a dextran sulfate ligand is bound to porous cellulose beads. Liposorber is used to treat familial hypercholesterolemia (FH), peripheral arterial disease (PAD), and focal segmental glomerulosclerosis (FGS): Selesorb is used to treat systemic lupus erythematosus (SLE). Treatment utilizing both columns is being used effectively in patients with refractory disease that is resistant to pharmacotherapy.

Beta2-microglobulin-selective adsorbent column (Lixelle) for the treatment of dialysis-related amyloidosis.

Abstract:  Lixelle is a direct hemoperfusion‐type adsorbent column developedfor selective elimination of β2‐microglobulin(β2‐m) from the circulating blood of patientswith dialysis‐related amyloidosis (DRA). Lixelle S‐35, that has a column volume of 350 mL, efficiently eliminates β2‐m andimproves symptoms of DRA such as joint pain and nocturnal awakening.The performance of Lixelle S‐15, that has a column volume of 150 mL,is dependent on the dialysis membrane used in combination with theadsorbent column in a hemodialysis circuit. The combination of S‐15 anda dialysis membrane with a high β2‐m clearance eliminatesan amount of β2‐m that is nearly equal to the amount removed by using S‐35. Treatment with S‐15 for 6 months improved joint pain with an efficacy similar to that observed when using S‐35. The major adverse effectswere hypotension and decrease in hematocrit, and these incidenceswere much less in S‐15 compared to S‐35.

Anti-DNA antibody kinetics following selective removal by adsorption using dextran sulphate cellulose columns in patients with systemic lupus erythematosus

The aim of this study is to determine by mathematical analysis which of two models, the one‐ or the two‐compartment model, more closely approximates the kinetics of anti‐dsDNA following immunoadsorption procedures in patients with systemic lupus erythematosus. Titers of anti‐dsDNA were measured at specified intervals after apheresis to each model by nonlinear least‐squares methods, and Akaikes Information Criterion (AIC) was calculated to determine which model most approximately described the kinetics.

Anti-dsDNA antibody kinetics during in vivo apheresis in systemic lupus erythematosus patients and in an in vitro apheresis model

Levels of anti‐dsDNA measured just after an immunoadsorption procedure in systemic lupus erythematosus (SLE) patients are sometimes paradoxically larger than those measured just before the procedure. A 1:100 in vitro single‐compartment immunoadsorption system model was devised to determine which of two models, one‐ or two‐compartment, more closely approximates the kinetics of anti‐dsDNA during apheresis procedures. Ten SLE patients were employed in this study. A total of 4,100 ml of plasma was passed through the dextran sulfate cellulose columns during one clinical apheresis session. In eight of ten patients, the log of RIA‐measured anti‐dsDNA titers decreased linearly as treated plasma volume increased, in both the clinical procedure and the experimental model. The mean adsorption efficacy in the clinical apheresis procedure and in the in vitro model was 0.37 and 0.27, respectively. However, in one patient the RIA‐measured level of anti‐dsDNA increased during the apheresis procedure; this phenomenon was mirrored in the model (definitely a single pool model). In contrast, the level of anti‐dsDNA, as measured by ELISA, decreased in accordance with the increase of treated plasma volume in both the clinical and the in vitro apheresis procedures. Therefore, an increased titer of anti‐dsDNA as measured by RIA immediately following clinical apheresis cannot be accounted for exclusively by an inflow of antibodies from a secondary (extravascular) pool into the circulating plasma. In short, a one‐compartment model is applicable and an explanation must be sought elsewhere.

Microbial production of (R)-3-halolactic acid from (±)-3-halo-1,2-propanediol

Abstract Microbial oxidation of (±)-3-halo-1,2-propanediol was studied and it was found that several microorganisms accumulated ( R )-3-halolactic acid. Geotrichum loubieri CBS 252.61 produced the most and gave optically pure ( R )-3-chlorolactic acid and ( R )-3-bromolactic acid from the corresponding diols.