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Biomedical subjects

S Akimoto

Publications and source records attributed to S Akimoto.

At least 19 recordsLinked to original sources

Modified windmill porphyrin arrays: coupled light-harvesting and charge separattion, conformational relaxation in the S1 state, and S2-S2 energy transfer.

The architecture of windmill hexameric zinc(II) -porphyrin array 1 is attractive as a light-harvesting functional unit in view of its three-dimensionally extended geometry that is favorable for a large cross-section of incident light as well as for a suitable energy gradient from the peripheral porphyrins to the meso-meso-linked diporphyrin core. Three core-modified windmill porphyrin arrays 2-4 were prepared for the purpose of enhancing the intramolecular energy-transfer rate and coupling these arrays with a charge-separation functional unit. Bisphenylethynylation at the meso and meso' positions of the diporphyrin core indeed resulted in a remarkable enhancement in the intramolecular S1-S1 energy transfer in 2 with tau=2 approximately 3 ps, as revealed by femtosecond time-resolved transient absorption spectroscopy. The fluorescence lifetime of the S2 state of the peripheral porphyrin energy donor determined by the fluorescence up-conversion method was 68 fs, and thus considerably shorter than that of the reference monomer (150 fs), suggesting the presence of the intramolecular energy-transfer channel in the S2 state manifold. Such a rapid energy transfer can be understood in terms of large Coulombic interactions associated with the strong Soret transitions of the donor and acceptor. Picosecond time-resolved fluorescence spectra and transient absorption spectra revealed conformational relaxation of the S1 state of the diporphyrin core with tau = 25 ps. Upon photoexcitation of models 3 and 4, which bear a naphthalenetetracarboxylic diimide or a meso-nitrated free-base porphyrin attached to the modified diporphyrin core as an electron acceptor, a series of photochemical processes proceeded, such as the collection of the excitation energy at the diporphyrin core, the electron transfer from the S1 state of the diporphyrin to the electron acceptor, and the electron transfer from the peripheral porphyrins to the diporphyrin cation radical, which are coupled to provide a fully charge-separated state such as that in the natural photosynthetic reaction center. The overall quantum yield for the full charge separation is better in 4 than in 3 owing to the slower charge recombination associated with smaller reorganization energy of the porphyrin acceptor.

Journal Article↗

Determination of serum prostate-specific antigen-alpha1-antichymotrypsin complex for diagnosis of prostate cancer in Japanese cases.

OBJECTIVE: The clinical utility of the determination of serum prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) for the diagnosis of prostate cancer, especially in cases in the diagnostic gray zone, is still unclear. MATERIAL AND METHODS: With the use of a newly approved enzyme immunoassay for the detection of PSA-ACT, 907 sera, including those from non-urological benign and malignant diseases, were analysed. RESULTS: Serum values of PSA-ACT in non-prostate cancer males increased according to age from the 40s to 70s. The serum values were high only in the patients with prostatic diseases and, in prostate cancer patients, the values became high as the clinical stage progressed. By receiver-operating characteristic analysis significantly better results in PSA-ACT than total PSA were observed. In the group with a total PSA of 2-20 ng/ml, the detection of PSA-ACT showed better results, although not significantly so, than the free-to-total PSA ratio. CONCLUSIONS: The detection of PSA-ACT showed a high clinical utility in the diagnosis of prostate cancer. Therefore, it may replace total PSA determination.

Adult↗

Genetic variation in 16S-23S rDNA internal transcribed spacer regions and the possible use of this genetic variation for molecular diagnosis of Bacteroides species.

The structural variation in 16S-23S rDNA internal transcribed spacer regions (ITS) among Bacteroides species was assessed by PCR amplification and sequencing analysis, and its possible use for molecular diagnosis of these species was evaluated. Ninety strains of the genus Bacteroides, including the species B. distasonis, B. eggerthii, B. fragilis, B. ovatus, B. thetaiotaomicron, B. uniformis and B. vulgatus, produced one to three ITS amplification products with sizes ranging from 615 to 810 bp. Some Bacteroides strains could be differentiated at species level on the basis of ITS amplification patterns and restriction fragment length polymorphism (RFLP) analysis using a four-nucleotide-recognizing enzyme, Msp I. The results of sequence analysis of ITS amplification products revealed genes for Ile-tRNA and Ala-tRNA in all strains tested. The nucleotide sequence, except for that in tRNA-coding regions, was highly variable and characteristic for each species, but a common sequence among B. fragilis, B. thetaiotaomicron and B. ovatus was observed. A digoxigenin-labeled oligonucleotide probe (named FOT1), which was designed from this conserved sequence, specifically hybridized to the ITS amplification products from B. fragilis, B. thetaiotaomicron and B. ovatus. These results suggest that the ITS region is a useful target for the development of rapid and accurate techniques for identification of Bacteroides species.

Bacteroides↗

B chromosomes, translocation between B and autosomes, and C-heterochromatin polymorphism of the grasshopper Podisma sapporensis Shir. (Orthoptera, Acrididae) in Hokkaido, northern Japan.

Seven categories of B chromosomes found in the brachypterus grasshopper Podisma sapporensis from Hokkaido populations differ in structure, size, and C-band content. The interchange between B and one autosome from M3 and sporadically M7 was observed in most of the populations examined. Such an interaction between standard and non-standard chromosomal set provides an insight into the integration of supernumerary chromosome. In addition, C-heterochromatin polymorphism was also identified in male karyotypes in some populations. These facts indicate P. sapporensis is a highly polymorphic species from the cytogenetic point of view.

Animals↗

Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/Waf1)

Alterations in the functions of vascular endothelial cells (ECs) induced by fluid shear stress may play a pivotal role in both the development and prevention of vascular diseases. We found that DNA synthesis of bovine aortic and human umbilical vein ECs, determined by [(3)H]thymidine incorporation, was inhibited by steady laminar shear stress (5 and 30 dyne/cm(2)). This growth inhibition due to shear stress was associated with suppression of cell transition from the G(1) to S phase of the cell cycle. Therefore, we studied G(1)-phase events to find the molecules responsible for this cell cycle arrest. Shear stress inhibited the phosphorylation of a retinoblastoma protein (pRb) and the activity of cyclin-dependent kinase (cdk) 2 and cdk4, which phosphorylate pRb. The level of cdk inhibitor p21(Sdi1/Cip1/Waf1) protein, but not that of p27(Kip1), increased as a result of shear stress, and the amount of p21 protein associated with cdk2 also increased, although the protein level of cdk2 was unchanged. Shear stress markedly elevated the mRNA level of p21, and this elevation in mRNA faded after the release of cells from shear stress, concomitant with a recovery of DNA synthesis. These results suggest that steady laminar shear stress induces cell cycle arrest by upregulating p21. Derangement of the steady laminar flow may release cells from this inhibition and induce cell proliferation, which, in turn, may cause atherosclerosis through the induction of EC stability disruption.

Animals↗

Integrin alpha6beta4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer.

BACKGROUND & AIMS: Because alterations of integrin expression in cancers contribute to cancer cell biology, we analyzed the association between the potential for peritoneal dissemination and integrin expression. METHODS: The dissemination potential of 10 human gastric cancer cell lines in mice with severe combined immunodeficiency (SCID) was compared with the expression of various integrins. The relationship between integrin expression and peritoneal dissemination was also investigated in surgically resected gastric cancer cases. RESULTS: The level of integrin beta4 subunit expression was inversely correlated with dissemination potential. Introduction of a full-length complementary DNA (cDNA) for beta4 subunit into cancer cells showing negligible beta4 subunit expression markedly suppressed peritoneal dissemination and inhibition of endogenous integrin alpha6beta4 by introduction of a cytoplasmic domain-deleted beta4 subunit cDNA into cells showing high expression of beta4 subunit promoted peritoneal dissemination. Apoptosis, which was histologically evident in peritoneal nodules of SCID mice, was induced in the cells with high beta4 subunit expression by attachment to laminin and stimulation with growth factors in vitro. An immunohistochemical study of specimens from 120 cases of primary gastric cancer showed that patients with beta4 subunit-positive tumors exhibited peritoneal dissemination only infrequently (P < 0.0001) and had a better outcome (P < 0.01). CONCLUSIONS: These results indicate that integrin alpha6beta4 is both a suppressor and a predictive marker for peritoneal dissemination in gastric cancer.

Animals↗

Disaccharide analysis of skin glycosaminoglycans in atrophoderma of Pasini and Pierini.

There are divergent opinions as to whether atrophoderma of Pasini and Pierini (APP) is a nosologic entity or a primary atrophic morphoea. In this study, we used high performance liquid chromatography to analyse the skin disaccharide contents of glycosaminoglycan (GAG) in two patients with APP and compared the results with those from a typical atrophic morphoea patient. Perilesional uninvolved skin was used as a control in each patient. In the atrophic phase morphoea, both the total amount of disaccharide per skin punch-biopsy and the amount of DeltaDi-4S(DS) - the main disaccharide unit of dermatan sulphate - per mg dry weight were increased. These changes were consistent with sclerotic phase morphoea. In contrast, the total amount of disaccharide per skin punch-biopsy was decreased and the amount of DeltaDi-4S(DS) per mg dry weight was decreased or unchanged in APP. Our results suggest that GAG metabolism in APP may be unique and quite different from that in morphoea.

Adolescent↗

Outbreak of human parvovirus B19 in hospital workers.

We report an outbreak of human parvovirus B19 (HPV B19) infection affecting five nursing staff, four hospital office workers and one physiotherapist and its possible transmission between hospital staff. We investigated the presence of the virus in serum specimens using a nested PCR assay to confirm HPV B19 infection. The viral genome was detected in serum specimens from a nurse with a rash and arthralgia and from three hospital office workers with a febrile illness. The DNA sequence of the PCR products from three staff members was identical. Our findings suggest that transmission of HPV B19 between hospital staff members occurred.

Adult↗

Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human colorectal cancer.

The membranous, cytoplasmic and nuclear levels of beta-catenin were evaluated immunohistochemically in archival tissue specimens from 96 Japanese patients with primary colorectal carcinoma who had undergone surgery. The relationships between beta-catenin and clinicopathological variables were analyzed statistically. Reduced beta-catenin immunoreactivity in the cell membranes of cancer cells was found in 70% of the tumors, and cytoplasmic and nuclear accumulation of beta-catenin were found in 68 and 66% of tumors, respectively. Significant correlations between cytoplasmic beta-catenin accumulation and the depth of invasion, venous invasion and focal dedifferentiation were observed. Cytoplasmic beta-catenin accumulation was also found to be a useful predictor of hematogenous metastasis (hazard ratio = 8.94, p = 0.054), though neither a reduced cell membrane level nor nuclear accumulation of beta-catenin correlated with metastasis.

Adenocarcinoma↗

Induction and suppression of endothelial cell apoptosis by sphingolipids: a possible in vitro model for cell-cell interactions between platelets and endothelial cells.

Because sphingosine (Sph) is actively incorporated into platelets and rapidly converted to sphingosine 1-phosphate (Sph-1-P), which is then released extracellularly, it is important to study the effects of Sph and Sph-1-P on endothelial cells from the viewpoint of platelet-endothelial cell interaction. In this study, we found that Sph, as well as ceramide, induces apoptosis in human umbilical vein endothelial cells (HUVECs). In contrast, Sph-1-P acts as a HUVEC survival factor; this bioactive lipid was shown to protect HUVECs from apoptosis induced by the withdrawal of growth factors and to stimulate HUVEC DNA synthesis. In metabolic studies, [3H]Sph, incorporated into HUVECs, was converted to [3H]Cer and further to [3H]sphingomyelin in a time-dependent manner, whereas [3H]Sph-1-P formation from [3H]Sph was weak and transient. These findings in HUVECs are very different from those of platelets, which possess a highly active Sph kinase but lack Sph-1-P lyase. As a result, platelets abundantly store Sph-1-P, whereas HUVECs contain much less Sph-1-P. Finally, HUVECs, in contrast to platelets, failed to release Sph-1-P extracellularly, indicating that HUVECs themselves are not able to supply the survival factor Sph-1-P, but receive it from activated platelets. Our results suggest that platelets may maintain the integrity of endothelial cells by incorporating Sph and releasing Sph-1-P.

Acetic Anhydrides↗

Fluorescence properties of chlorophyll d-dominating prokaryotic alga, acaryochloris marina: studies using time-resolved fluorescence spectroscopy on intact cells

Antenna components and the primary electron donor of the photosystem (PS) II in the Chlorophyll (Chl) d-dominating prokaryote, Acaryochloris marina, were studied using time-resolved fluorescence spectroscopy in the ps time range. By selective excitation of Chl a or Chl d, differences in fluorescence properties were clearly resolved. At physiological temperature, energy transfer was confirmed by a red shift of emission maximum among PS II antenna components, and the equilibrium of energy distribution among Chl a and Chl d was established within 30 ps. A fluorescence component that can be assigned to delayed fluorescence (DF) was observed at 10 ns after the excitation; however, it was not necessarily resolved by the decay kinetics. At -196 degrees C, a red shift of emission maximum was reproduced but the equilibrium of energy distribution was not detected. DF was resolved in the wavelength region corresponding to Chl a by spectra and by decay kinetics. The lifetime of the DF was estimated to be approx. 15 ns, and the peaks were located at 681 and 695 nm, significantly shorter wavelengths than those of Chl d. These findings strongly suggest that an origin of DF is Chl a, and Chl a is most probably the primary electron donor in the PS II reaction center (RC). These results indicate that the constitution of PS II RC in this alga is essentially identical to that of other oxygenic photosynthetic organisms.

Journal Article↗

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

BACKGROUND: Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS: The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS: The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS: These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Aged↗

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗

Pattern of progression and survival in hormonally treated metastatic prostate cancer.

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.

Aged↗