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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 127 records · Page 7Linked to original sources

Early and long-term results of cardiovascular surgery in octogenarians.

The purpose of this study was to evaluate characteristics and outcomes of octogenarians undergoing cardiovascular surgery with cardiopulmonary bypass in a Japanese population. Thirty-one consecutive patients over 80 years of age underwent coronary artery bypass grafting 19 (61%), combined coronary artery bypass grafting and ventricular septal perforation closure 1 (3%), valve replacement 3 (10%), and prosthetic graft replacement 8 (26%). The early mortality rate was 16.1%. Survival estimates were 74% after 1 year, 74% after 3 year, and 64% after 5 years. Emergency and urgent cases involved 16 (51.6%), and 2 patients (6.5%), respectively. Multivariate analyses revealed that predictors of early mortality was preoperative left ventricular ejection fraction. Predictors of hospital death (within 3 months after surgery) were preoperative renal dysfunction, intraaortic balloon pumping, and age. Predictors of late mortality were chronic lung disease and age. Twenty-one patients expected to have died before surgery were living at home, and 9 (40.9%) patients were completely autonomous. Multivariate analyses revealed diabetes mellitus and a small number of bypass grafts were predictive risk factors for postoperative autonomy. Thus, cardiovascular surgery can be performed in octogenarians under 85 years of age with a favorable long-term outcome, when appropriately applied in selective octogenarians without significant comorbidity. If patients are over 85 years of age or have significant comorbidity, clinical treatment recommendations should be individually tailored while evaluating the risk of having or not having surgery and their life expectancy. QOL of survivors was almost satisfactory and significantly improved compared with a preoperative state.

Age Factors↗

[Characterization of cryoglobulin, M protein, low molecular weight IgM in a patient with chronic hepatitis C and type II mixed cryoglobulinemia].

The common extrahepatic manifestation of hepatitis C virus(HCV) infection is mixed cryoglobulinemia. We have analyzed serum cryoglobulin, IgM and various antibody activities from a patient with chronic hepatitis C and type II cryoglobulinemia. Cryoprecipitates were consisted of polyclonal IgG and monoclonal IgM-kappa with rheumatoid factor activity. About 20% of total IgM was found to be low molecular weight IgM by gel-filtration and SDS-PAGE. The anti-streptolysin O(ASO) activity measured by Latex agglutination method was found to be markedly elevated despite normal activity by Rantz-Randell method. The patient's serum has revealed to react against bovine gamma globulin, which crosslinked streptolysin O to Latex particles, in a nonspecific manner. Phenotypic analysis of the surface markers on abnormal lymphoid cells from peripheral blood and bone marrow showed monoclonal expansion of B-cell lineage by flow cytometry. The patient was treated with interferon-alpha, which resulted in an improvement of liver dysfunction, decreased amounts of cryoglobulin and IgM. It was concluded that the patient has suffered from lymphoproliferative disorder, namely HCV infection-associated primary macroglobulinemia.

Aged↗

[Management of medical practice at home].

We present here how medical practice is managed at the patients home. Medical care at home is conducted in conjunction with a variety of professionals who provide health care in the community. The use of computers allows us to easily download information, and transfer it from the clinic to community services. Fluid replacement, total parenteral nutrition, palliative treatment of pain in cancer patients, management of urethral catheters, and other skills that are carried out at home would be stated.

Home Care Services, Hospital-Based↗

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗

Synthesis and properties of aminoacylamido-AMP: chemical optimization for the construction of an N-acyl phosphoramidate linkage.

This paper describes the design and synthesis of a new type of aminoacyl-adenylate analogue (aa-AMPN) having an N-acyl phosphoramidate linkage where the oxygen atom of the mixed anhydride bond of aminoacyl-adenylate (aa-AMP) is replaced by an amino group. This new type of aa-AMP analogue is expected to be useful as material for studies on the recognition mechanism of the aminoacylation of tRNA and other biochemical reactions. The condensation of phosphoramidite derivatives of carboxamides with nucleoside derivatives failed, because the activated phosphoramidite derivatives reacted with not only the hydroxyl groups but also another reactive species. An alternative approach was examined by the reaction of 5'-O-phosphoramidite adenosine derivatives with carboxamide derivatives. The TBTr and TSE groups were chosen for protection of the amino group of amino acid amides and the phosphate group, respectively. Detailed studies revealed that the use of 5-(3,5-dinitrophenyl)-1H-tetrazole as an activating catalyst of phosphoramidites resulted in rapid condensation within 10 min to give fully protected aa-AMPN derivatives. No side reaction occurred. Deprotection of these products via a two-step procedure gave aa-AMPN derivatives in good yields. It also turned out that aa-AMPNs thus obtained are stable under both acidic and basic conditions, such as 0.1 M HCl (pH 1.0) and 0.1 M NaOH (pH 13.0).

Adenosine Monophosphate↗

Supramolecular photochirogenesis. 2. Enantiodifferentiating photoisomerization of cyclooctene included and sensitized by 6-O-modified cyclodextrins

Supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to the chiral (E)-isomer (1E) via inclusion and sensitization by modified alpha-, beta-, and/or gamma-cyclodextrin derivatives, possessing benzoate (2a, 3a, 4a), isomeric phthalates (3b-d), and tethered benzamide (3e) chromophores, has been investigated in aqueous methanol solutions at varying temperatures. The photostationary-state 1E/1Z ratios obtained upon sensitization with 2-4 in 1:1 water-methanol reached 0.4-0.8, which are higher than the value of ca. 0.25 reported for sensitizations by conventional alkyl benzoates in hydrocarbon solvents, although the ratio was reduced to 0.2-0.4 in water or methanol. The sensitizations of 1Z by alpha- and gamma-cyclodextrin benzoates (2a, 4a) with size-mismatched cavities gave 1E of poor enantiomeric excesses (ee's) smaller than 3 and 5%, respectively. In contrast, beta-cyclodextrin derivatives (3a-e) afforded much higher ee's of up to 24%, depending on the solvent composition. Thus, the modification of cyclodextrin with a sensitizing group successfully enhanced the product through the excited-state supramolecular interaction within the cavity. Interestingly, the product ee's obtained with benzoate 3a and methyl phthalate 3b are not a simple function of either temperature or solvent, but are nicely correlated with the host occupancy or the percentage of occupied host. This means that the entropy factor plays an insignificant role in this supramolecular photochirogenesis system, which is in sharp contrast to the decisive role of entropy in the conventional (nonsupramolecular) counterpart performed in homogeneous solutions, where an inversion of product chirality by temperature variation is reported to occur.

Journal Article↗

A regulator of transcriptional elongation controls vertebrate neuronal development.

The development of distinct vertebrate neurons is defined by the unique profiles of genes that neurons express. It is accepted that neural genes are regulated at the point of transcription initiation, but the role of messenger RNA elongation in neural gene regulation has not been examined. Here we describe the mutant foggy, identified in a genetic screen for mutations that affect neuronal development in zebrafish, that displayed a reduction of dopamine-containing neurons and a corresponding surplus of serotonin-containing neurons in the hypothalamus. Positional cloning disclosed that Foggy is a brain-enriched nuclear protein that is structurally related to the transcription elongation factor Spt5 (refs 5-12). Foggy is not part of the basic transcription apparatus but a phosphorylation-dependent, dual regulator of transcription elongation. The mutation disrupts its repressive but not its stimulatory activity. Our results provide molecular, genetic and biochemical evidence that negative regulators of transcription elongation control key aspects of neuronal development.

Amino Acid Sequence↗

Synthesis and conformational properties of oligonucleotides incorporating 2'-O-phosphorylated ribonucleotides as structural motifs of pre-tRNA splicing intermediates.

To synthesize oligonucleotides containing 2'-O-phosphate groups, four kinds of ribonucleoside 3'-phosphoramidite building blocks 6a-d having the bis(2-cyano-1,1-dimethylethoxy)thiophosphoryl (BCMETP) group were prepared according to our previous phosphorylation procedure. These phosphoramidite units 6a-d were not contaminated with 3'-regioisomers and were successfully applied to solid-phase synthesis to give oligodeoxyuridylates 15, 16 and oligouridylates 21, 22. Self-complementary Drew-Dickerson DNA 12mers 24-28 replaced by a 2'-O-phosphorylated ribonucleotide at various positions were similarly synthesized. In these syntheses, it turned out that KI(3) was the most effective reagent for oxidative desulfurization of the initially generated thiophosphate group to the phosphate group on polymer supports. Without using this conversion step, a tridecadeoxyuridylate 17 incorporating a 2'-O-thiophosphorylated uridine derivative was also synthesized. To investigate the effect of the 2'-phosphate group on the thermal stability and 3D-structure of DNA(RNA) duplexes, T(m) measurement of the self-complementary oligonucleotides obtained and MD simulation of heptamer duplexes 33-36 were carried out. According to these analyses, it was suggested that the nucleoside ribose moiety phosphorylated at the 2'-hydroxyl function predominantly preferred C2'-endo to C3'-endo conformation in DNA duplexes so that it did not significantly affect the stability of the DNA duplex. On the other hand, the 2'-modified ribose moiety was expelled to give a C3'-endo conformation in RNA duplexes so that the RNA duplexes were extremely destabilized.

Base Sequence↗

Dorsal spinal cord inhibits oligodendrocyte development.

Oligodendrocytes are the myelinating cells of the mammalian central nervous system. In the mouse spinal cord, oligodendrocytes are generated from strictly restricted regions of the ventral ventricular zone. To investigate how they originate from these specific regions, we used an explant culture system of the E12 mouse cervical spinal cord and hindbrain. In this culture system O4(+) cells were first detected along the ventral midline of the explant and were subsequently expanded to the dorsal region similar to in vivo. When we cultured the ventral and dorsal spinal cords separately, a robust increase in the number of O4(+) cells was observed in the ventral fragment. The number of both progenitor cells and mature cells also increased in the ventral fragment. This phenomenon suggests the presence of inhibitory factor for oligodendrocyte development from dorsal spinal cord. BMP4, a strong candidate for this factor that is secreted from the dorsal spinal cord, did not affect oligodendrocyte development. Previous studies demonstrated that signals from the notochord and ventral spinal cord, such as sonic hedgehog and neuregulin, promote the ventral region-specific development of oligodendrocytes. Our present study demonstrates that the dorsal spinal cord negatively regulates oligodendrocyte development.

Animals↗

Molecular design of crown ethers. 21.(1,2) synthesis of novel double-armed benzo-15-crown-5 lariats and their complexation thermodynamics with light lanthanoid nitrates in acetonitrile

Three new disubstituted benzo-15-crown-5 derivatives (3-5) have been synthesized from 4',5'-bis(bromomethyl)benzo-15-crown-5 (2) and the corresponding alkanols in the presence of Na(2)S(2), and their complexation thermodynamics with light lanthanoid(III) nitrates (La-Gd) have been studied in anhydrous acetonitrile at 25 degrees C. Plots of K(S) against the reciprocal ionic diameter of lanthanoid exhibited monotonically declining pattern for the parent benzo-15-crown-5 (1) and 3 but showed a characteristic peak at Ce(3+) for 4 and 5. It is interesting to note that the simple extension of the alkyl side chains in 4 and 5 can alter the cation selectivity profiles of 1 and 3. Possessing two 2-oxapropyl groups, 3 gave a comparable K(S) for La(3+) but a significantly decreased K(S) for Ce(3+) compared with the corresponding values for 1, thus exhibiting an exceptionally high La(3+)/Ce(3+) selectivity of 11. Thermodynamically, the complexation of lanthanoid perchlorates with 1 is absolutely entropy-driven in acetonitrile, while the complexation of lanthanoid nitrates with 3-5 is primarily driven by exothermic enthalpy changes with accompanying moderate entropic gain or small entropic loss.

Journal Article↗

Perfect switching of photoreactivity by acid: photochemical decarboxylation versus transesterification of mesityl cyclohexanecarboxylate

Mesityl cyclohexanecarboxylate has been photodecarboxylated upon excitation at 254 nm to form cyclohexylmesitylene in good yield in neutral acetonitrile solutions. In the presence of a catalytic amount of the acid and ethanol as a nucleophile, however, the same compound undergoes facile transesterification upon irradiation, affording its ethyl ester in almost quantitative yield.

Journal Article↗

Synthesis and properties of oligonucleotides having a phosphorus chiral center by incorporation of conformationally rigid 5'-cyclouridylic acid derivatives.

This paper describes the design and synthesis of a conformationally rigid dimer building block Umpc3Um as a chiral center at the phosphate group with the S/N junction where c3 refers to a propylene bridge linked between the uracil 5-position and 5'-phosphate group of pUm. The extensive H1 NMR analysis of Umpc3Um suggests that the 5'-upstream Um has predominantly a C2'-endo conformation and the pc3Um moiety exists almost exclusively in a C3'-endo conformation. The absolute configuration of the diastereomers Umpc3Um(fast) (8a) and Umpc3Um(slow) (8b) was determined by CD spectroscopy as well as computer simulations. The oligonucleotides U4[Umpc3Um(fast)]U4 (13a) and U4[Umpc3Um(slow)]U4 (13b) incorporating 8a and 8b were synthesized by use of the phosphoramidite building blocks 11a and 11b, respectively. The Tm experiments of the duplexes formed between these modified oligomers and the complementary oligomers imply that the modified oligomer 13a having Umpc3Um(fast) has the Sp configuration at the chiral phosphoryl group.

Circular Dichroism↗

Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is one of the many known X-linked mental retardation syndromes. Mutations in the ATR-X gene (ATRX) that encodes a putative global transcription factor have been identified in patients with ATR-X as well as those with other forms of X-linked mental retardation syndrome. To better understand the genetic basis of ATR-X, we investigated nine patients with the ATR-X phenotype from eight independent Japanese families for mutations in ATRX. We identified seven missense mutations, including six novel mutations, all of which were located either in the N-terminal region corresponding to the putative zinc finger domain (N179S, P190L, V194I, and R246C) or in the C-terminal region corresponding to the helicase domain (V1552F, L1645S, and Y1847C). R246C was found in two independent patients. Furthermore, we investigated the origin of the mutations in seven mothers. Five mothers were found to be carriers, and two were not, indicating de novo origin of the mutations. When we compared clinical manifestations with respective mutations, we could not find apparent phenotype-genotype correlation. Therefore, the putative zinc finger domain and the helicase domains may have similar functional significance for the function of ATRX.

Adult↗

Initial Stage Dynamics of Bridging Flocculation of Polystyrene Latex Spheres with Polyethylene Oxide.

The kinetics of bridging flocculation of polystyrene latex (PSL) particles induced by addition of excess polyethylene oxide (PEO) in the initial stage was studied using standardized mixing flow generated in an end-over-end rotation apparatus. To clarify the effect of the rate of polymer supply, flocculation experiments were performed by changing polymer concentration (C(p)). As was found in previous investigation, the progress of flocculation is divided into two stages. The first stage is characterized by an enhancement of the rate of flocculation by polymer addition. The increase in polymer concentration results in a higher enhancement but in a shorter duration for this stage. In the second stage, the flocculation is essentially stopped due to the appearance of steric stabilization. It was found that the ultimate degree of flocculation goes through a maximum against C(p). That is, when C(p)>==1.0 ppm, the ultimate degree of flocculation decreases with increased C(p). In this region, a clear crossover from the first stage to the second stage was observed. In the extreme case, evidence of a slight setback of flocculation was confirmed, which implies the breakup of metastable bridges by the application of additional fluid shear. When C(p)<==1.0 ppm, the ultimate degree of flocculation decreases with decreased C(p). The crossover from the first stage to the second stage appears more gradual at lower C(p). These results were observed irrespective of ionic strength. This result was interpreted as the elimination of a bare surface due to the spreading of a steric layer of adsorbed polymer. The characteristic time for reconformation of the polymer at a bare colloidal surface was estimated to be a few seconds. Copyright 2000 Academic Press.

Journal Article↗

Synthesis of 4-thiouridine, 6-thioinosine, and 6-thioguanosine 3',5'-O-bisphosphates as donor molecules for RNA ligation and their application to the synthesis of photoactivatable TMG-capped U1 snRNA fragments.

4-Thiouridine, 6-thioguanosine, and 6-thioinosine 3',5'-bisphosphates (9, 20, and 28) were synthesized in good yields by considerably improved methods. In the former two compounds, uridine and 2-N-phenylacetylguanosine were converted via transient O-trimethylsilylation to the corresponding 4- and 6-O-benzenesulfonyl intermediates (2 and 13), which, in turn, were allowed to react with 2-cyanoethanethiol in the presence of N-methylpyrrolidine to give 4-thiouridine (3) and 2-N-phenylacetyl-6-thioguanosine derivatives (14), respectively. In situ dimethoxytritylation of these thionucleoside derivatives gave the 5'-masked products 4 and 15 in high overall yields from 1 and 11. 6-S-(2-Cyanoethyl)-5'-O-(4,4'-dimethoxytrityl)-6-thioinosine (23) was synthesized via substitution of the 5'-O-tritylated 6-chloropurine riboside derivative 22 with 2-cyanoethanethiol. These S-(2-cyanoethyl)thionucleosides were converted to the 2'-O-(tert-butyldimethylsilyl)ribonucleoside 3'-phosphoramidite derivatives 7, 18, and 26 or 3',5'-bisphosphate derivatives 8, 19, and 27. Treatment of 8, 19, and 27 with DBU gave thionucleoside 3',5'-bisphosphate derivatives 9, 20, and 28, which were found to be substrates of T4 RNA ligase. These thionucleoside 3',5'-bisphosphates were examined as donors for ligation with m3(2,2,7) G5'pppAmUmA, i.e., the 5'-terminal tetranucleotide fragment of U1 snRNA, The 4-thiouridine 3',5'-bisphosphate derivative 9 was found to serve as the most active substrate of T4 RNA ligase with a reaction efficiency of 96%.

Guanosine↗

Synthesis and properties of 2'-O-methyl-2-thiouridine and oligoribonucleotides containing 2'-O-methyl-2-thiouridine.

A new method for the synthesis of 2'-O-methyl-2-thiouridine (s2Um) found in thermophilic bacterial tRNA was developed. Structural properties of s2Um and s2Um(p)U were studied by using 1H NMR spectroscopy. A modified nonaribonucleotide (RNA*: 5'-CGUUs2UmUUGC-3') was synthesized to study the base-recognition ability of s2Um in formation of RNA-RNA and RNA DNA duplexes. The UV melting experiments revealed that RNA*-RNA and RNA*-DNA duplexes having an s2U-A base pair are more stable than those having a U-A base pair. On the contrary, the thermal stability of RNA*-RNA and RNA*-DNA duplexes having an s2U-G wobble base pair was much lower than that of the unmodified duplexes having a natural U-G base pair. It is concluded that s2Um has higher selectivity toward A over G than unmodified U.

Archaea↗

Total syntheses of (-)-methyl atis-16-en-19-oate, (-)-methyl kaur-16-en-19-oate, and (-)-methyl trachyloban-19-oate by a combination of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement.

Asymmetric total syntheses of (-)-methyl atis-16-en-19-oate (1c), (-)-methyl kaur-16-en-19-oate (2c), and (-)-methyl trachyloban-19-oate (3c) have been achieved by employing a hybrid strategy of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement. The common synthetic intermediate 5 was prepared from 2-allylcyclohexanone (4) with 98% ee using d'Angelo's asymmetric Michael addition. A series of functional group modifications in 5 via palladium-catalyzed cycloalkenylation led to (+)-14, which had already been prepared by us as racemate. (-)-Methyl atis-16-ene-19-oate (1c) was generated via homoallyl-homoallyl radical rearrangement. On the other hand, Wolff-Kishner reduction of 18 followed by esterification yielded (-)-methyl kaur-16-en-19-oate (2c) together with (-)-methyl trachyloban-19-oate (3c).

Alkaloids↗