Search PubMed⌕ Search

Biomedical subjects

S Oda

Publications and source records attributed to S Oda.

At least 55 records · Page 3Linked to original sources

Synthesis of methyl ursodeoxycholate via microbial reduction of methyl 7-ketolithocholate with Eubacterium aerofaciens JCM 7790 grown on two kinds of carbon and hydride sources, glucose and mannitol.

Eubacterium aerofaciens JCM 7790, which produces 7beta-hydroxysteroid dehydrogenase [7beta-HSDH], efficiently catalyzed the reduction of methyl 7-ketolithocholate [Me-7KLCA] to afford methyl ursodeoxycholate [Me-UDCA] in an anaerobic interface bioreactor. For the high accumulation of Me-UDCA, the best supplement of carbon and hydride source to the ABCM medium (glucose content, 0.3 wt.%) was screened because glucose strongly repressed 7beta-HSDH production. The supplementation of cellobiose, mannitol, sodium gluconate, and sodium pyruvate was effective to improve the production of Me-UDCA, although many mono- and disaccharides, such as fructose, sucrose, and lactose, strongly repressed 7beta-HSDH activity. A phosphate buffer was used as the aqueous phase in the carrier to avoid the lowering of medium pH in the carrier caused by the accumulation of organic acids via fermentation by E. aerofaciens. Thus, the productivity of Me-UDCA was elevated by the combination of glucose and mannitol as carbon and hydride sources and by using a phosphate buffer.

Journal Article↗

Preparation of methyl ursodeoxycholate via microbial reduction of methyl 7-ketolithocholate in an anaerobic interface bioreactor.

An interface bioreactor, which is a device for the microbial transformation of water-insoluble substrates, was applied to an anaerobic bioconversion for the first time. Methyl 7-ketolithocholate [Me-7KLCA] was reduced with the human intestinal bacterium Eubacterium aerofaciens JCM 7790 in a convenient anaerobic interface bioreactor using a nutrient agar plate placed in a GasPak pouch. The resulting methyl ursodeoxycholate [Me-UDCA] is a precursor of ursodeoxycholic acid, which is used as a cholesterol gallstone-dissolving agent. The reaction conditions were optimized, and ABCM medium and dihexyl ether were selected as the best carrier and reaction solvent, respectively. The toxicity of the bile acid esters toward the human intestinal bacterium was effectively alleviated in the interface bioreactor, in which the maximal concentrations of Me-7KLCA and Me-UDCA in the dihexyl ether layer respectively reached to 12.0 and 6.1 g/l.

Journal Article↗

Synthesis of (S)-ibuprofen via enantioselective degradation of racemic ibuprofen with an isolated yeast, Trichosporon cutaneum KPY 30802, in an interface bioreactor.

An interface bioreactor was used for the enantioselective degradation of (RS)-ibuprofen (IBU). An isolated yeast, Trichosporon cutaneum KPY 30802, preferentially degraded (R)-IBU to accumulate (S)-isomer. The addition of hydroquinone (10 mM) into a hydrophilic carrier was effective for the elevation of enantiomeric excess and the repression of excess degradation of (S)-IBU (E value, 9.3).

Journal Article↗

Coupling of fermentation and esterification: microbial esterification of decanoic acid with ethanol produced via fermentation.

Two different kinds of bioprocess, ethanol fermentation and subsequent microbial esterification, were coupled using Issatchenkia terricola IFO 0933 in an interface bioreactor. The strain produced ethyl decanoate (Et-DA) by esterification of exogenous decanoic acid (DA) with ethanol produced via fermentation. The efficiency of the new coupling system depended on the concentration of glucose in a carrier and DA in an organic phase (decane) in an agar plate interface bioreactor. Optimum glucose content and DA concentration were 4% and 29 mM, respectively.

Decanoic Acids↗

A new double coupling system: synthesis of citronellyl acetate via transacetylation to citronellol from acetyl coenzyme A produced from glucose and free fatty acids.

A double coupling system, which couples metabolism of glucose and transacetylation, is a unique procedure for the production of acetic esters. In the novel coupling system described in this article, acetyl coenzyme A (acetyl-CoA) was supplied via metabolism of both glucose and exogenous saturated fatty acids. While short and middle chain fatty acids having C4-8 were very biotoxic, myristic acid (C14) was effectively used as a source of acetyl-CoA.

Acetyl Coenzyme A↗

A case of aldosterone-producing adrenocortical adenoma associated with preclinical Cushing's syndrome and hypersecretion of parathyroid hormone.

A rare case of aldosterone-producing adrenocortical adenoma with preclinical Cushing's syndrome and hypersecretion of parathyroid hormone (PTH) is described. A 64-year-old male patient had a history of hypertension for two decades and hypokalemia for 4 years. He suffered from left hemiparesis and aphasia due to cerebral hemorrhage, but his appearance was not Cushingoid. His plasma renin activity was below the normal range, while plasma aldosterone concentration was high. They did not respond to furosemide-upright test. His plasma cortisol level in the morning was at the upper limit of the normal range, but it did not show a diurnal rhythm nor was it suppressed by 1 mg and 8 mg of dexamethasone. Computed tomography showed a low density tumor in the right adrenal gland. An adrenal scintigram under dexamethasone treatment revealed an uptake of the tracer on the right side, and plasma aldosterone and cortisol concentrations in the adrenal vein were higher on the right side than on the opposite. The diagnosis of right aldosterone-producing adrenal adenoma with an autonomous production of cortisol was confirmed by right adrenalectomy. Histological findings showed an adenoma consisting mostly of clear cells, but that the nests of compact cells were scattered. Analysis of an extract from the adenoma revealed that the adenoma contained an excess amount of aldosterone and that the cortisol/corticosterone ratio was higher than that of aldosterone-producing adenoma. Both serum calcium and PTH levels remained high one year after adrenalectomy. Ultrasonography revealed the swelling of a parathyroid gland on the left side, indicating the coexistence of an autonomous hyperparathyroidism.

Adenoma↗

Histological characteristics of the pelage skin of rough fur mice (C3H/HeJ- ruf/ruf).

Pelage skin of C3H/HeJ mice homozygous at an autosomal recessive mutant locus, rough fur (ruf) which is located on chromosome 9, was histologically analyzed. Sebaceous glands synthesizing lipids were larger in the mutant mice than in controls in an examination by Sudan IV staining. Electron microscopic analysis of the sebaceous gland showed that lipid droplets were denser in mutant mice than in control mice, and that they were irregular in shape in ruf mice while those of controls were round. Our results suggested that rough fur (ruf) mice might be an animal model for hyperlipogenesis of the pelage skin.

Animals↗

A new mouse model with cochleo-saccular type inner ear defects.

We found a new inner ear mutant exhibiting abnormal behavior, such as circling and head shaking, in a breeding stock of SJL/J mice. The traits are inherited in a simple autosomal-recessive fashion. Animals homozygous for the responsible gene, designated cosa, show no startle response to sounds and an inability to swim. In the inner ears of cosa/cosa homozygous, but not +/cosa heterozygous adults, histopathological features of severe damage that are typical for 'cochleo-saccular' or 'spotting' mutants have been demonstrated. We suggest here that the abnormal mice carry a mutation of a gene that is developmentally switched on in the early stages of development and is involved in endolymph homeostasis.

Animals↗

Central and peripheral visual reaction time of soccer players and nonathletes.

Visual Reaction Time (RT) was measured by presenting three different sizes of stimulus to the central and peripheral fields of vision in 6 soccer players and 6 nonathletes. An electromyogram was recorded from the flexor digitorum superficialis muscle of the responding forearm. Peripheral visual RT was longer in comparison to central visual RT due to an increment in Premotor Time. The soccer players showed shorter Premotor Times during central and peripheral visual RT tasks than nonathletes, suggesting that the soccer players are better able to respond quickly to a stimulus presented to peripheral as well as central positions.

Adult↗

Efficacy of the novel selective platelet-derived growth factor receptor antagonist CT52923 on cellular proliferation, migration, and suppression of neointima following vascular injury.

Exaggerated or inappropriate signaling by the platelet-derived growth factor receptor (PDGFR) tyrosine kinase has been implicated in a wide variety of diseases. Thus, a series of piperazinyl quinazoline compounds were identified as potent antagonists of the PDGFR by screening chemical libraries. An optimized analog, CT52923, was shown to be an ATP-competitive inhibitor that exhibited remarkable specificity when tested against other kinases, including all members of the closely related PDGFR family. The PDGFRs and stem cell factor receptor were inhibited with an IC(50) of 100 to 200 nM, while 45- to >200-fold higher concentrations of CT52923 were required to inhibit fms-like tyrosine kinase-3 and colony-stimulating factor-1 receptor, respectively. Other receptor tyrosine kinases, cytoplasmic tyrosine kinases, serine/threonine kinases, or members of the mitogen-activated protein kinase pathway were not significantly inhibited at 100- to 1000-fold higher concentrations. In addition, this compound also demonstrated specificity for inhibition of cellular responses. Platelet-derived growth factor-induced smooth muscle cell migration or fibroblast proliferation was found to be blocked by CT52923 with an IC(50) of 64 and 280 nM, respectively, whereas 50- to 100-fold higher concentrations were required to inhibit these responses when induced with fibroblast growth factor. To investigate the effect of CT52923 on PDGFR signaling, in vivo studies demonstrated that CT52923 could significantly inhibit neointima formation following carotid artery injury by oral administration in the rat. Therefore, PDGFR antagonism by CT52923 could be a viable strategy for the prevention of clinical restenosis or the treatment of other human diseases involving PDGFR signaling.

Angioplasty, Balloon↗

[A study of the relation between providing healthcare information and behavior changes of people in Japan. Parental behavior changes after receiving information about the sudden infant death syndrome].

OBJECTIVE: Considering the lack of evidence concerning the relationship between providing healthcare information and behavior of people in Japan, we utilized a questionnaire to survey the parents of infants to evaluate behavior change after receiving information about the Sudden Infant Death Syndrome (SIDS). METHODS: A questionnaire about SIDS information was administered in 234 municipalities in Niigata, Gifu, Shizuoka, and Hiroshima Prefectures and in Yokohama City in November and December of 1999 to 14,879 parents who visited for the 18-month health examination of their children. The questionnaire did not ask for the participants' names. Logistic regression analysis was used to study the connection between behavior change and SIDS information sources. RESULTS: 10,900 parents returned the questionnaire to give a 73.3% response rate, 19.0% of these receiving information about SIDS risk factors from hospitals or clinics, 3.7% from public health centers, and 9.2% from their friends. More received information from the mass media such as TV programs, which provided the main source for 71.1% of the parents. The degree of behavior change was evaluated after adjustment for variables concerning a variety of information sources and other appropriate factors such as the age and sex of parents and the number of their children. We found that receiving information from hospitals or clinics significantly influences behavior changes for all kinds of risk factors. Information from public health centers, baby-care groups, and friends influenced behavior changes relevant to the risk factors for feeding methods, sleeping position, and parents' smoking. There was no relation between receiving information from the mass media and behavior change of parents. CONCLUSIONS: The mass media provide far more information than do medical facilities, public health centers, baby-care groups and personal contacts but the latter played much more effective roles in making parents change their baby care behavior. These results point to an obvious discrepancy between efficiency in providing information and the degree of behavior change elicited. We should thus take the source of information and the target population into consideration when we examine the best way to provide healthcare information for people in the future.

Adult↗

NAD(P)+-NAD(P)H models. 90. Stereoselection controlled by electronic effect of a carbonyl group in oxidation of NAD(P)H analog.

4-Monodeuterated NAD(P)H model compounds (1,4,6,7-tetrahydro-1,6,11-trimethyl-5-oxo-5H-benzo[c]pyrido[2,3-e]az epin; 11Me-MMPAH) have been oxidized with a series of p-benzoquinone and its derivatives in the presence of Mg2+. The models have an axial chirality with respect to the orientation of carbonyl dipole, the dihedral angle of which is larger than 55 degrees out of the plane of dihydropyridine ring. Without Mg2+, the anti- (with respect to the carbonyl dipole) hydrogen is 3 to 32 times more reactive than the corresponding syn-hydrogen, whereas, when Mg2+ is present in the system, the selectivity is shifted toward the syn-preferency. Mg2+ plays the role of a Lewis acid catalyst to control the stereochemistry at the same time as it catalyzes the reaction.

Catalysis↗

Synthesis and applications of [1-(15)N]-labeled 4,6-dimethyl-4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide as a useful tool for mechanistic investigations.

[1-(15)N]-Labeled 4,6-dimethyl-4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide (1-(15)N1) was easily prepared by nitration of commercially available 6-amino-1,3-dimethyl-1H-pyrimidine-2,4-dione using 15N-enriched nitric acid followed by an intramolecular oxidative cyclization with iodosylbenzene diacetate under mild conditions. On the basis of the experimental results using 1-(15)N1, the formation of 8-phenyltheophylline (3), the 1,3-dimethylalloxazines (4: n = 0, 1), and 1,3,7,9-tetramethyl-1H,9H-pyrimido[5,4-g]pteridine-2,4,6,8-tetraone++ + (5) in the thermal reaction of the N-oxide 1 with benzylamine, aniline, or piperidine, and the generation of NO or NO-related species in the reaction with N-acetylcysteamine were reasonably explained by considering the initial attack of the employed nucleophiles on the 3a-position of 1.

Aniline Compounds↗

Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation rolling Nagoya (tg(rol)).

Recent genetic analyses have revealed an important association of the gene encoding the P/Q-type voltage-dependent Ca(2+) channel alpha(1A) subunit with hereditary neurological disorders. We have identified the ataxic mouse mutation, rolling Nagoya (tg(rol)), in the alpha(1A) gene that leads to a charge-neutralizing arginine-to-glycine substitution at position 1262 in the voltage sensor-forming segment S4 in repeat III. Ca(2+) channel currents in acutely dissociated Purkinje cells, where P-type is the dominant type, showed a marked decrease in slope and a depolarizing shift by 8 mV of the conductance-voltage curve and reduction in current density in tg(rol) mouse cerebella, compared with those in wild-type. Compatible functional change was induced by the tg(rol) mutation in the recombinant alpha(1A) channel, indicating that a defect in voltage sensor of P/Q-type Ca(2+) channels is the direct consequence of the tg(rol) mutation. Furthermore, somatic whole-cell recording of mutant Purkinje cells displayed only abortive Na(+) burst activity and hardly exhibited Ca(2+) spike activity in cerebellar slices. Thus, in tg(rol) mice, reduced voltage sensitivity, which may derive from a gating charge defect, and diminished activity of the P-type alpha(1A) Ca(2+) channel significantly impair integrative properties of Purkinje neurons, presumably resulting in locomotor deficits.

Action Potentials↗

Efficient repair of A/C mismatches in mouse cells deficient in long-patch mismatch repair.

A previously unrecognized mismatch repair activity is described. Extracts of immortalized MSH2-deficient mouse fibroblasts did not correct most single base mispairs. The same extracts carried out efficient repair of A/C mismatches. A/G mispairs were less efficiently corrected and there was no significant repair of A/A. MLH1-defective mouse extracts also repaired an A/C mispair. A/C correction by Msh2(-/-) mouse cell extracts was not affected by antibodies against the PMS2 protein, which inhibited long-patch mismatch repair. A/C repair activity is thus independent of MutSalpha, MutSbeta and MutLalpha. A/C mismatches were corrected 5-fold more efficiently by extracts of Msh2 knockout mouse cells than by comparable extracts prepared from hMSH2- or hMLH1-deficient human cells. MSH2-independent A/C correction by mouse cell extracts did not require a nick in the circular duplex DNA substrate. Repair involved replacement of the A and was associated with the resynthesis of a limited stretch of </=25 bases of DNA.

Adaptor Proteins, Signal Transducing↗

Spatiotemporal analysis of Ca(2+) waves in relation to the sperm entry site and animal-vegetal axis during Ca(2+) oscillations in fertilized mouse eggs.

Fertilized mouse eggs exhibit repetitive rises in intracellular Ca(2+) concentration ([Ca(2+)](i)) necessary for egg activation. Precise spatiotemporal dynamics of each [Ca(2+)](i) rise were investigated by high-speed Ca(2+) imaging during early development of monospermic eggs. Every [Ca(2+)](i) rise involved a Ca(2+) wave. In the first Ca(2+) transient, [Ca(2+)](i) increased in two steps separated by a "shoulder" point, suggesting two distinct Ca(2+) release mechanisms. The first step was a Ca(2+) wave that propagated from the sperm-fusion site to its antipode in 4-5 s (velocity, approximately 20 microm/s in most eggs). The second step from the shoulder to the peak was a nearly uniform [Ca(2+)](i) rise of 12-15 s. A slight cytoplasmic movement followed the Ca(2+) wave in the same direction and recovered in 25-35 s. These characteristics changed as follows, as Ca(2+) oscillations progressed during the second meiosis up to their cessation at the stage of pronuclei formation ( approximately 3 h after fertilization). (1) The duration of Ca(2+) transients became shorter. (2) The shoulder point shifted to higher levels and the first step occupied most of the rising phase. (3) The rate of [Ca(2+)](i) rise became greater and wave speeds increased up to 80-100 microm/s or more. (4) The transient cytoplasmic movement always resulted from the Ca(2+) wave, although its displacement became smaller. (5) The Ca(2+) wave initiation site was freed from the sperm-fusion or -entry site and eventually localized in the cortex of the vegetal hemisphere. Since the shift of the wave initiation site to the vegetal cortex is observed in fertilized eggs of nemertean worms and ascidians, this might be an evolutionarily conserved feature.

Animals↗

Comparison of Sepsis-related Organ Failure Assessment (SOFA) score and CIS (cellular injury score) for scoring of severity for patients with multiple organ dysfunction syndrome (MODS).

OBJECTIVE: To evaluate the usefulness of cellular injury score (CIS) and Sepsis-related Organ Failure Assessment (SOFA) score for determination of the severity of multiple organ dysfunction syndrome (MODS). DESIGN: A prospective observational study. SETTING: A medical and surgical intensive care unit (ICU) of a teaching hospital. PATIENTS: Forty-seven consecutive MODS patients. MEASUREMENTS AND RESULTS: SOFA score and CIS were measured every day for 12 months for 47 MODS patients. Comparison was made of the SOFA score and CIS for usefulness in the scoring of severity of MODS in 26 survivors and 21 non-survivors. In addition, receiver operating characteristics (ROC) analysis was used to determine the usefulness of these two indexes as predictors of prognosis. No significant differences were found on admission between the survivors and non-survivors, but significant differences between the two subgroups (p < 0.001) were found in maximum value within 1 week after admission and maximum value during the course of treatment for both indexes. Analysis of changes after admission indicated that significant differences between survivors and non-survivors began to appear on day 3 of admission for both indexes; at that time SOFA score began to deteriorate in the non-survivors while CIS began to improve in the survivors. ROC analysis demonstrated that the area under the ROC curve was 0.769 for SOFA scores and 0.760 for CIS. CONCLUSIONS: Both SOFA score and CIS sequentially reflected the severity of MODS. Furthermore, they were comparable in diagnostic value as predictors of prognosis. These findings may indicate the possibility that MODS is a summation of effects of cellular injury. In addition, sequential evaluation of both SOFA score and CIS would provide a more accurate prediction of prognosis than conventional methods.

Aged↗