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Biomedical subjects

Ken Sakai

Publications and source records attributed to Ken Sakai.

At least 19 recordsLinked to original sources
PubMed2006

Chemotactic cytokine receptor 5 (CCR5) gene promoter polymorphism (59029A/G) is associated with diabetic nephropathy in Japanese patients with type 2 diabetes: a 10-year longitudinal study.

We previously showed that polymorphisms of the promoter area of chemokine receptor 5 (CCR5) gene (59029G/A) and its agonist, regulated upon activation, normal T-cell expressed and secreted (RANTES) gene (-28C/G) were new candidates for susceptibility to diabetic nephropathy. The aim of this study was to confirm the effect of these polymorphisms on the development and progression of diabetic nephropathy. We performed a 10-year retrospective study of 191 Japanese type 2 diabetic patients with normoalbuminuria at baseline. The subjects were classified into two groups: (1) those with persistent normoalbuminuria (group N) and (2) those with progression from normoalbuminuria to microalbuminuria or overt proteinuria (group P). Then, their association with CCR5 59029G/A and RANTES -28C/G polymorphisms was assessed. The frequency of the RANTES -28G(+) genotype did nor differ between the two groups, but the CCR5 59029A(+) genotype had a significantly higher frequency in group P than in group N (83% versus 71%, p=0.04). By discriminant analysis, only the CCR5 59029A(+) genotype showed an independent positive correlation with the onset or progression of nephropathy (p=0.03, odds ratio=2.41, 95% CI=1.09-5.33). Therefore, the CCR5 59029A(+) genotype seems to be related the etiology of diabetic nephropathy in Japanese type 2 diabetics.

Aged↗
PubMed2006

Strict glycemic control ameliorates the increase of carotid IMT in patients with type 2 diabetes.

The aim of this study was to investigate the effect of strict glycemic control on the carotid artery intima-media thickness (IMT) in type 2 diabetic patients who initially had good glycemic control (HbA1c between 5.8 and 6.4 %). The subjects were 67 patients showing deterioration of the mean HbA1c over 3 years by more than 0.2% from baseline (D group) and 33 subjects showing improvement of the mean HbA1c by more than 0.2% from baseline (A group). The clinical characteristics and annual change of IMT during the observation period were compared between the two groups in a 3-year retrospective longitudinal study. The baseline characteristics and the mean values of BMI, blood pressure, and serum lipids during the study period did not differ significantly between the two groups. However, the mean HbA1c of A group was significantly lower than that of D group (5.67 +/- 0.10 vs. 6.28 +/- 0.08, mean +/- SE, p<0.001). The adjusted annual increase rate of IMT was significantly less in A group than in D group (-0.035 +/- 0.019 vs. 0.036 +/- 0.015 mm, M +/- SEM, p<0.001). These results indicate that further improvement of glycemic control from a good HbA1c value can prevent an increase of IMT in type 2 diabetic patients.

Adult↗
PubMed2006

Therapeutic efficacy of mitiglinide combined with once daily insulin glargine after switching from multiple daily insulin regimen of aspart insulin and glargine in patients with type 2 diabetes mellitus.

Mitiglinide is novel class of rapid-acting insulin secretagogues, which have been widely used alone or in combination with other oral hypoglycemic drugs to improve postprandial hyperglycemia in early type 2 diabetes. While mitiglinide enhances postprandial requirement of insulin, the efficacy of mitiglinide combined with insulin has yet to be established. We investigated the efficacy of mitiglinide combined with insulin glargine, the first soluble insulin analog that has a flat and prolonged effect. After control with the intensive regimen (daily aspart insulin and glargine), 30 inpatients with type 2 diabetes were switched to premeal mitiglinide combined with once daily insulin glargine (mitiglinide regimen), and daily profiles of blood glucose level were compared under each regimen. Fifteen patients showed similar control of hyperglycemia with mitiglinide regimen and intensive insulin regimen, assessed by M value (<32), while the remaining 15 showed worsening under the mitiglinide regimen. The patients who were well controlled with mitiglinide regimen were significantly younger (51.9 +/- 16.0 years, p<0.005) and heavier (body mass index: 25.7 +/- 3.3 kg/m(2), p<0.05) than those who were not (67.9 +/- 8.7 and 23.0 +/- 3.1, respectively). Moreover, insulin doses of aspart per body weight were significantly fewer in effective group than in ineffective group. Duration of diabetes was shorter in the effective group, albeit insignificantly. Previous treatment before starting intensive insulin regimen, such as insulin and sulfonylurea, was not different between the two groups. Our results suggest that mitiglinide plus insulin glargine combination therapy is useful for lowering both fasting and postprandial hyperglycemia in a subpopulation of type 2 diabetes. The long-term effects of such treatment need to be established in future studies.

Adult↗
PubMed2005

Syntheses and properties of emissive iridium(III) complexes with tridentate benzimidazole derivatives.

A series of novel emissive Ir(III) complexes having the coordination environments of [Ir(N--N--N)2]3+, [Ir(N--N--N)(N--N)Cl]2+, and [Ir(N--N--N)(N--C--N)]2+ with 2,6-bis(1-methyl-benzimidazol-2-yl)pyridine (L1, N--N--N), 1,3-bis(1-methyl-benzimidazol-2-yl)benzene (L2H, N--C--N), 4'-(4-methylphenyl)-2,2':6',2' '-terpyridine (ttpy, N--N--N), and 2,2'-bipyridine (bpy, N--N) have been synthesized and their photophysical and electrochemical properties studied. The Ir(III) complexes exhibited phosphorescent emissions in the 500-600 nm region, with lifetimes ranging from approximately 1-10 micros at 295 K. Analysis of the 0-0 energies and the redox potentials indicated that the lowest excited state of [Ir(L1)(L2)]2+ possessed the highest contribution of 3MLCT (MLCT = metal-to-ligand charge transfer) among the Ir(III) complexes, reflecting the sigma-donating ability of the tridentate ligand, ttpy < L1 < L2. The emission quantum yields (phi) of the Ir(III) complexes ranged from 0.037 to 0.19, and the highest phi value (0.19) was obtained for [Ir(L1)(bpy)Cl]2+. Radiative rate constants (k(r)) were 1.2 x 10(4) s(-1) for [Ir(ttpy)2]3+, 3.7 x 10(4) s(-1) for [Ir(L1)(bpy)Cl]2+, 3.8 x 10(4) s(-1) for [Ir(ttpy)(bpy)Cl]2+, 3.9 x 10(4) s(-1) for [Ir(L1)2]3+, and 6.6 x 10(4) s(-1) for [Ir(L1)(L2)]2+. The highest radiative rate for [Ir(L1)(L2)]2+ with the highest contribution of 3MLCT could be explained in terms of the singlet-triplet mixing induced by spin-orbit coupling of 5d electrons in the MLCT electronic configurations.

Journal Article↗
PubMed2005

Tissue transglutaminase at embryo-maternal interface.

CONTEXT: Tissue transglutaminase (tTG) has a high affinity for fibronectin (FN) and is a coreceptor of both beta1 and beta3 integrin subunits. Considering the notion that FN and integrins have critical roles during the implantation process, this study was undertaken to elucidate the expression pattern and the potential physiological function of tTG at the embryo-maternal interface. METHODS: The primary cultures of human placentas from 15 legal elective abortions at the first trimester of normal pregnancies and endometrial biopsies of 12 female patients in the midluteal phase as well as normal trophoblastic cell lines (CRL) were employed to address these issues using several approaches, such as scanning and transmission electron microscopies, immunostaining for light and electron microscopies, western blotting, and function assays using GRGDSP hexapeptide and an antibody against tTG. RESULTS: The results demonstrated tTG expression on uterine pinopodes and lamellipodia of extravillous trophoblasts. The colocalization of tTG with beta1 and beta3 integrins and its interaction with alpha(v)beta3 integrin and integrin-associated proteins at focal adhesions of the extravillous trophoblasts were illustrated in the results of immunofluorescence, immunoblot, and coimmunoprecipitation studies. Furthermore, function assays revealed that tTG mediated the adhesion and spread of the placental cells on intact FN-coated and 42- and 110-kDa FN fragment-coated wells. CONCLUSION: In conclusion, our findings demonstrated for the first time that tTG actively participates in adhesion events at the embryo-maternal interface through its interaction with FN, at least in part, by activating integrin-signaling pathways.

Blotting, Western↗
PubMed2005

Total synthesis of epoxyquinols A, B, and C and epoxytwinol A and the reactivity of a 2H-pyran derivative as the diene component in the Diels-Alder reaction.

Full details of two versions of the total synthesis of epoxyquinols A, B, and C and epoxytwinol A (RKB-3564D) are described. In the first-generation synthesis, the HfCl(4)-mediated diastereoselective Diels-Alder reaction of furan with Corey's chiral auxiliary has been developed. In the second-generation synthesis, a chromatography-free preparation of an iodolactone, by using acryloyl chloride as the dienophile in the Diels-Alder reaction of furan, and the lipase-mediated kinetic resolution of a cyclohexenol derivative have been developed. This second-generation synthesis is suitable for large-scale preparation. A biomimetic cascade reaction involving oxidation, 6pi-electrocyclization, and then Diels-Alder dimerization is the key reaction in the formation of the complex heptacyclic structure of epoxyquinols A, B, and C. Epoxytwinol A is synthesized by the cascade reaction composed of oxidation, 6pi-electrocyclization, and formal [4 + 4] cycloaddition reactions. A 2H-pyran, generated by oxidation/6pi-electrocyclization, acts as a good diene, reacting with several dienophiles to afford polycyclic compounds in one step. An azapentacyclic compound is synthesized by a similar cascade reaction composed of the four successive steps: oxidation, imine formation, 6pi-azaelectrocyclization, and Diels-Alder dimerization.

Ascomycota↗
PubMed2005

Post-transplant early recurrent proteinuria in patients with focal glomerulosclerosis--angiotensin II immunostaining and treatment outcome.

We reviewed the transplantation data and results of histopathological studies with additional angiotensin II (AII) immunostaining of renal graft biopsies of nine cases (10 grafts) with recurrent proteinuria and three controls without recurrent proteinuria that received renal transplantation for primary focal segmental glomerulosclerosis (FSGS) between 1986 and 2002. Recurrent FSGS was confirmed in six grafts from nine cases by light microscopy. In cases with recurrent proteinuria, loss of graft function was noted in all six renal grafts received between 1986 and early 1992 but in none of four grafts received between late 1992 and 2002. Two of four patients of the late group but none of those of the early group received angiotensin converting enzyme (ACEI) or angiotensin II receptor blocker (ARB) with plasma exchange (PE). In control cases without proteinuria, AII immunostaining was detected in tubules but not in glomeruli in 1-hour biopsies as well as later on. In cases with recurrent proteinuria, AII immunostaining was detected in both tubules and glomeruli, although glomerular AII staining was not observed in 1-hour biopsies. Our results suggest that effective treatment of post-transplantation recurrent FSGS requires ACEI or ARB with PE in the absence of another etiology.

Adolescent↗
PubMed2005

[Recurrence of sarcoidosis in a hemodialysis patient confirmed by abnormal calcium metabolism].

28-year-old man hospitalized for a fever of unknown origin. This patient was already diagnosed as neurosarcoidosis proven by brain biopsy in 1997, then entered chronic hemodialysis therapy in 2002. The data showed hypercalcemia without taking any calcium agent and vitamin D, also showed suppressed intact-parathyroid hormone and normalized 1,25-dihydroxyvitamin D even the condition of end stage renal failure. Recurrence of sarcoidosis was made in this hospitalization. The laboratory data as well as symptom improved after taking oral prednisolone. We reported the case of recurrent sarcoidosis in a hemodialysis patient confirmed by abnormal calcium metabolism.

Adult↗
PubMed2004

First bent form for the hydroxo-bridged cis-diammineplatinum(II) dimer [Pt(2)(NH(3))(4)(micro-OH)(2)](ClO(4))(2).

The third crystal structure containing the hydroxo-bridged cis-diammineplatinum(II) dimer has been determined for a perchlorate salt of the complex, [Pt(2)(NH(3))(4)(micro-OH)(2)](ClO(4))(2). However, the dinuclear cations in the nitrate and the carbonate salts, [Pt(2)(NH(3))(4)(micro-OH)(2)](NO(3))(2) [Faggiani, Lippert, Lock & Rosenberg (1977). J. Am. Chem. Soc. 99, 777-781] and [Pt(2)(NH(3))(4)(micro-OH)(2)](CO(3)).H(2)O [Lippert, Lock, Rosenberg & Zvagulis (1978). Inorg. Chem. 17, 2971-2975], were reported to possess a nearly planar geometry. The cation in the title perchlorate salt has been found to possess an exceptional bent form in which two Pt coordination planes within the dimer are tilted at an angle of 151.7 (1) degrees to one another. The diplatinum entity has a syn orientation with regard to the conformation of two hydroxo bridges, in part due to the one-dimensional hydrogen-bonding network achieved in the crystal structure. DFT MO investigations have also been carried out to reveal that the planar-bent selection could be induced by the anti-syn selection at the H(hydroxo) atoms. Comparison has also been made between the geometrical features of the three salts from the viewpoint of the orientation of H(hydroxo) atoms.

Carbonates↗
PubMed2004

Di-mu-pivalamidato-kappa4N:O;O:N-bis[(2,2'-bipyridine-kappa2N,N')(sulfato-kappaO)platinum(III)] tetrahydrate in a head-to-tail isomerism.

The title compound, [Pt(2)(III)(C(5)H(10)NO)(2)(SO(4))(2)(C(10)H(8)N(2))(2)].4H(2)O, is the first reported example of a complex in which an amidate-bridged Pt(bpy) dimer is stabilized in the oxidation level of Pt(III) (bpy is 2,2'-bipyridine). The asymmetric unit consists of one half of the formula unit with a twofold axis passing through the center of the dimer. The intradimer Pt(III)-Pt(III) bond distance [2.5664 (6) A] is comparable to those reported for alpha-pyridonate-bridged cis-diammineplatinum(III) dimers [2.5401 (5)-2.5468 (8) A; Hollis & Lippard (1983). Inorg. Chem. 22, 2605-2614], in spite of the close contact between the bpy planes within the dimeric unit. The axial Pt-O(sulfate) distance is 2.144 (7) A.

Journal Article↗
PubMed2004

Bis(2,2'-bipyridine-kappa2N,N')(1,10-phenanthroline-kappa2N,N')ruthenium(II) tetracyanoplatinate(II).

In the title compound, [Ru(C(10)H(8)N(2))(2)(C(12)H(8)N(2))][Pt(CN)(4)], cations and anions alternate along the a axis to afford a one-dimensional network. The one-dimensional character arises from the pi-pi stacking as well as from the electrostatic interactions formed between the phen (1,10-phenanthroline) and [Pt(CN)(4)](2-) units. Two adjacent one-dimensional chains form further stacks based on the pi-pi stacking interactions between the phen moieties, where the interplanar spacing is 3.50 (1) A.

Journal Article↗
PubMed2004

Bis[tris(2,2'-bipyridine-kappa2N,N')ruthenium(II)] hexacyanoferrate(III) chloride octahydrate.

In the title compound, [Ru(II)(C(10)H(8)N(2))(3)](2)[Fe(III)(CN)(6)]Cl.8H(2)O, the [Ru(bpy)(3)](2+) (bpy is 2,2'-bipyridine) cations and water molecules afford intriguing microporous honeycomb layers, while the [Fe(CN)(6)](3-) anions and the remainder of the water molecules form anionic sheets based on extensive hydrogen-bonding networks. The cationic and anionic layers alternate along the c axis. The Fe atom in [Fe(CN)(6)](3-) lies on an inversion centre and the axial cyano ligands are hydrogen bonded to the water molecules encapsulated within the micropores [N.O = 2.788 (5) A], giving an unusual interpenetration between the cationic and anionic layers. On the other hand, the in-plane cyano ligands are relatively weakly hydrogen bonded to the water molecules [N.O = 2.855 (7) and 2.881 (8) A] within the anionic sheets.

Journal Article↗
PubMed2004

Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants.

This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-kappaB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-kappaB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 +/- 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 +/- 0.9 vs. 0.9 +/- 0.8, p < 0.01), although no significant differences were observed in NF-kappaB activation. Specimens with Banff acute rejection (AR) grade > or = 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well-functioning (serum creatinine < 1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68-positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.

Adult↗
PubMed2003

A head-to-head isomer of di-mu-pivalamidato-kappa4N,O-bis[(1,10-phenanthroline-kappa2N,N')platinum(II)] dinitrate dihydrate.

In the title compound, [Pt(2)(C(5)H(10)NO)(2)(C(12)H(8)N(2))(2)](NO(3))(2)*-2H(2)O, the intradimer Pt-Pt distance is relatively short [2.8489 (17) A], which must be due to the strong intramolecular pi-pi-stacking interactions between the phenanthroline moieties. The dimers stack along the c axis, forming one-dimensional columns in which very intriguing d-d, pi-pi and d-pi interactions exist. Although the dimer-dimer Pt...Pt distances are very long [4.340 (2) and 4.231 (2) A], some short interdimer Pt...C contacts leading to strong interdimer associations are found [3.325 (19) and 3.402 (19) A].

Journal Article↗