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Biomedical subjects

A Ando

Publications and source records attributed to A Ando.

At least 55 records · Page 3Linked to original sources

Production of 105Rh-EDTMP and its bone accumulation.

105Rh has favorable physical characteristics as a radiotherapeutic nuclide. Carrier-free 105Rh can be produced by the neutron activation of 104Ru followed by beta decay of 105Ru. It was clarified that carrier-free 105Rh can be produced in quantities and the purity necessary for chemical and clinical investigations of its use as a nuclide for radiotherapy. 105Rh-EDTMP was simply obtained from 105Rh3+ and EDTMP by heating for 30 min in boiling water, giving a radiochemical yield of > 99%. Dissociation of radioactivity assessed by paperchromatography was negligible for up to 5 days after its preparation. In animals, 105Rh-EDTMP showed rapid blood clearance and selective uptake in the bone. Hence, 105Rh-EDTMP is thought to be a promising therapeutic agent for the treatment of pain due to bone metastases.

Animals↗

Adsorption and pharmacokinetics of cyclosporin A in relation to mode of infusion in bone marrow transplant patients.

Two main factors that affect the pharmacokinetics of cyclosporin A (CsA) during 24-h durable intravenous (DIV) administration have been reported, namely physiological changes after bone marrow transplantation, and blood sampling through indwelling lines. In addition, it has been found that infusion sets made of polyvinyl chloride (PVC) markedly adsorb CsA. We conducted in vitro adsorption studies of CsA on infusion sets, and the administration routes that are used in the treatment of patients with bone marrow transplantation. We also examined the effects of administration route on CsA pharmacokinetics in clinical practice. The in vitro adsorption study using 30-mm segments of lumen from commercially available infusion sets showed that the degree of CsA adsorption per area of lumen made of PVC was significantly higher than that in those made of polyethylene (PE) or polybutadiene (PB), which showed no adsorption of CsA. Due to its adsorption, use of infusion sets made of PVC resulted in about a 40-50% loss of CsA dose, which affected the pharmacokinetic parameters during 24-h DIV, while those made of PE and PB did not. The use of non-PVC infusion sets should allow for accurate monitoring of CsA results, and provide cost benefit in the treatment of bone marrow transplantation.

Adsorption↗

Costs, emissions reductions, and vehicle repair: evidence from Arizona.

The Arizona inspection and maintenance (I/M) program provides one of the first opportunities to examine the costs and effectiveness of vehicle emission repair. This paper examines various aspects of emission reductions, fuel economy improvements, and repair costs, drawing data from over 80,000 vehicles that failed the I/M test in Arizona between 1995 and the first half of 1996. We summarize the wealth of data on repair from the Arizona program and highlight its limitations. Because missing or incomplete cost information has been a serious shortcoming for the evaluation of I/M programs, we develop a method for estimating repair costs when they are not reported. We find surprising evidence that almost one quarter of all vehicles that take the I/M test are never observed to pass the test. Using a statistical analysis, we provide some information about the differences between the vehicles that pass and those that do not. Older, more polluting vehicles are much more likely never to pass the I/M test, and their expected repair costs are much higher than those for newer cars. This paper summarizes the evidence on costs and emission reductions in the Arizona program, comparing costs and emissions reductions between cars and trucks. Finally, we examine the potential for more cost-effective repair, first through an analysis of tightening I/M cut points and then by calculating the cost savings of achieving different emission reduction goals when the most cost-effective repairs are made first.

Air Pollution↗

A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor.

BACKGROUND: Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55% of renal allograft recipients with recurrent IgA nephropathy (IgAN) at long-term follow-up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post-transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. METHODS: Twenty-one patients with post-transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin-converting enzyme (ACE) inhibitor treatment in post-transplant IgAN was also studied in 10 patients. RESULTS: The prevalence of glomeruli with adhesions and/or cellular crescents in primary IgAN was significantly greater than in post-transplant IgAN (P<0.05), but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post-transplant IgAN were significantly greater than in primary IgAN (P<0.05). The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post-transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post-transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE-inhibitor treatment (P<0.001). CONCLUSION: In post-transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE-inhibitor treatment in 10 patients showed favourable effects. A future long-term follow-up study is required to establish the effectiveness of ACE inhibitors in treatment of post-transplant IgAN.

Adult↗

Enhancement of dedifferentiation and myoid differentiation of retinal pigment epithelial cells by platelet derived growth factor.

AIMS: To clarify factor(s) involved in morphological dedifferentiation of retinal pigment epithelial (RPE) cells in vitro from mitotically quiescent hexagonal cells to flattened cells that lack epithelial characteristics and concurrent myoid differentiation. METHODS: RPE cells which retained their differentiated hexagonal morphology were isolated from bovine eyes by mechanical pipetting. Dedifferentiation and myoid differentiation of RPE cells were examined by microscopic observation and immunohistochemical analysis using antibodies against cytokeratin, an epithelial marker, and alpha smooth muscle actin, a marker of myoid differentiation. The contractile ability of RPE cells was evaluated by collagen gel contraction assay. RESULTS: Platelet derived growth factor (PDGF) enhanced morphological changes in the RPE from hexagonal-shaped cells to flattened cells. Coincident with this morphological alteration, the expression of cytokeratin in RPE cells decreased and expression of alpha smooth muscle actin began and was increased in a time dependent manner. These alterations were completely blocked by collagen synthesis inhibitors. Interleukin 1beta, transforming growth factor beta1, insulin-like growth factor I, and basic fibroblast growth factor had little or no effect on the dedifferentiation. PDGF also potentiated the RPE induced collagen gel contraction. CONCLUSIONS: These results demonstrate that PDGF enhanced the dedifferentiation of RPE cells, the initial step of proliferative vitreoretinopathy (PVR), as well as myoid differentiation and collagen gel contraction. PDGF may have a versatile role in the pathogenesis of PVR involving collagen synthesis.

Actins↗

The second eye of Japanese patients with unilateral exudative age related macular degeneration.

AIM: To clarify the incidence of choroidal neovascularisation (CNV) and predisposing findings for development of CNV in the second eye of Japanese patients with unilateral exudative age related macular degeneration (AMD). METHODS: The second eyes of unilaterally affected patients with exudative (neovascular) AMD treated in our clinic during the past 10 years (1988-97) were carefully followed up for more than a year. Evidence of CNV was confirmed by fluorescein and indocyanine green angiography. Macular lesions in patients, in whom CNV developed in the second eye, were retrospectively evaluated from patient records. RESULTS: 170 patients met the criteria. The average follow up period was 47 months (range 12-108 months). All patients were Japanese. CNV developed in the second eye in 12 (7%) of 170 patients, 30.3 months on average after the first examination. Cumulative incidence of developing CNV in the second eye using Kaplan-Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3% by 5 years, and was relatively low compared with that in white patients. CNV developed most frequently from serous pigment epithelial detachment (PED) in the macula (58%). Soft drusen were not prevalent and risk of developing CNV was not very high (18%). CONCLUSION: It was confirmed that there were some differences in the incidence and predisposing findings for CNV developing in AMD among Japanese and other Asian patients compared with those in white people. It is important to recognise these differences between the two populations to understand the pathogenesis and epidemiology of AMD.

Adult↗

Michael-type reaction of ethyl bromodifluoroacetate with alpha,beta- unsaturated carbonyl compounds in the presence of copper powder.

We have reported that the reaction of ethyl bromodifluoroacetate (1) with alkenyl iodides in the presence of copper powder gives ethyl alkenyldifluoroacetates. As an extension of this reaction, reaction of 1 with Michael acceptors in the presence of copper powder was examined and found to give 1,4-addition products selectively, unless the acceptor has a group stabilizing a radical intermediate, such as a phenyl group.

Copper↗

Synthesis of new synthons for organofluorine compounds from halothane containing sulfur functional groups.

To develop new synthons for the syntheses of organofluorine compounds, the treatment of Halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane, (1) with 4-methylbenzenethiol (2) in the presence of sodium hydride gave 1-chloro-2,2,2-trifluoroethyl 4-methylphenyl sulfide (3), which was oxidized with m-chloroperbenzoic acid (m-CPBA) to the corresponding sulfoxide (4) and sulfone (5). Reaction of 3 and 5 with allyltributyltin in the presence of 2,2'-azobis(isobutyronitrile) (AIBN) gave 1-(trifluoromethyl)-3-butenyl compounds (9, 11). Sulfoxide 4 was decomposed in this condition. The treatment of 3 with allyltrimethylsilane in the presence of Lewis acids gave 1-(trifluoromethyl)-3-butenyl compounds (9) in good yield. This result suggests that 4-methylphenylthio substituent stabilizes the alpha-carbocation effectively, though the trifluoromethyl group destabilizes it strongly. Aromatic compounds similarly reacted with 3 in the presence of titanium(IV) chloride to give 2-aryl-1,1,1-trifluoro-2-(4-methylphenylthio)ethanes. Thus, sulfur compounds derived from Halothane were found to be useful new synthons for organofluorine compounds.

Halothane↗

Effect of oxygen concentration on nitrogen removal by Nitrosomonas europaea and Paracoccus denitrificans immobilized within tubular polymeric gel.

Tubular gel reactors containing Nitrosomonas europaea and Paracoccus denitrificans, which remove nitrogen from solutions through a process of nitrification and denitrification, require oxygen for ammonia oxidation, the first and rate-limiting step in the process. To accelerate ammonia oxidation, high concentrations of oxygen were applied to the reactors instead of air. Although a 50% O2:N2 gas mixture and pure oxygen were both toxic to free N. europaea cells, they actually accelerated ammonia oxidation by N. europaea immobilized within the tubular gel. Indeed, the rate of ammonia oxidation by a tube exposed to pure oxygen was twice that of one exposed to 20% O2. When the distribution of N. europaea cells within the tubes was investigated using a fluorescently-labeled antibody, colonies were found on the external surface of the tube exposed to 20% O2, but were located at a depth of 120-300 microm from the external surface in the case of the tube exposed to pure oxygen. The region between the external surface of the gel and the colonies apparently acted as a barrier, reducing the diffusion of oxygen and thus protecting the cells from oxygen cytotoxicity.

Journal Article↗

Structures of ADP-ribosylated rifampicin and its metabolite: intermediates of rifampicin-ribosylation by Mycobacterium smegmatis DSM43756.

23-(O-ADP-Ribosyl)rifampicin [RIP-TAs (3, Na+ form), RIP-TAf (4, H+ form)] was obtained as an intermediate in the conversion process of rifampicin (1) to RIP-Mb (2) that is mediated by cell homogenates of Mycobacterium smegmatis DSM43756 or of Escherichia coli carrying a mycobacterial mono(ADP-ribosyl) transferase gene, in the presence of NADH. 23-[O-(5'-Phosphoribosyl)]rifampicin (5, RIP-TAp) was also obtained by the reaction of rifampicin with NADH in the presence of a homogenate of M. smegmatis. The structures of 3, 4, and 5 were determined by means of MS and NMR analyses.

ADP Ribose Transferases↗

[Two cases of thymic carcinoma effectively treated by preoperative chemotherapy].

A 67-year-old man was admitted with left pleural effusion on chest X-ray film. Chest CT scans showed an anterior mediastinal tumor, left pleural dissemination and pleural effusion. Percutaneous needle biopsy yielded a diagnosis of epitherial carcinoma. The patient underwent 3 courses of systemic chemotherapy (CDDP + ADM + VCR + CPA). At achievement of partial response, the tumor was completely resected. Examination of the resected tumor revealed partial response to chemotherapy. A 49-year-old woman was admitted our hospital with supraclavicular lymph nodes swelling. Chest CT scans showed an large mediastinal tumor. Percutaneous needle biopsy yielded a diagnosis of squamous cell carcinoma of thymus. The patient underwent 3 courses of systemic chemotherapy. At achievement of partial response, the tumor was completely resected. Examination of the resected tumor revealed partial response to chemotherapy. These cases indicate the usefulness of preoperative chemotherapy for advanced thymic carcinoma to reduce tumor size and to control local invasion, distant metastasis before operation.

Aged↗

[Three cases of pulmonary mucoepidermoid carcinoma].

Three cases of pulmonary mucoepidermoid carcinoma, which were surgically treated in our hospital, were reported. The first case was 28-year-old male, who had hemoptysis, underwent right upper lobectomy and mediastinal lymph node dissection on October 31, 1973. The tumor located and obstructed the ostium of right B2. The diameter was 2.3 x 1.8 cm. The second case was 63-year-old male, who had obstructive pneumonia, underwent left upper lobectomy and mediastinal lymph node dissection on November 18, 1998. The tumor located and obstructed the ostium of lingular bronchus, and the diameter was 1.8 x 1.2 cm. The third case was 25-year-old male, who had obstructive pneumonia, underwent left sleeve lower lobectomy and mediastinal lymph node dissection on May 26, 1999. The tumor located in ostium of left B6, and it obstructed lower bronchus and expanded into the lung. The diameter was 4 x 2 cm. All cases were diagnosed as low grade malignancy with no lymph node metastasis. The first case survived without recurrence at least 5 years as far as we followed, and the others are surviving until now without any signs of recurrence. These three cases were 0.19% of total resected lung cancers in our hospital from 1969 to 1999.

Adult↗

Cloned mice derived from somatic cell nuclei.

In 1997, a cloned sheep "Dolly" was produced by nuclear transfer of somatic cell. The first birth of cloned mice derived from some somatic cells were succeeded in 1998. At present, it is shown that somatic cells, cumulus cells, fibroblasts and Sertoli cells can be used to the study of cloned animal as nuclear donor. In this study investigation was designed to compare with efficiency on the production of cloned embryos by using the microinjection and the electrofusion methods for nuclear transfer. Oocyte enucleation was performed with a micromanipulator. The oocyte was held by holding pipette, and was enucleated using a beveled pipette. Microinjection method: Cell's nucleus injection was carried out by piezo-micromanipulator. Cytochalasin B treated cumulus cell was aspirated into a injection pipette, and was broken its plasma membrane using the injection pipette. Then, the cumulus cell was injected into the enucleated ooplasm directly. Electrofusion method: The cell was aspirated into a beveled pipette, and then an aspirated cell was inserted into perivitelline space. Then, the pair of enucleated oocyte and cell was fused using electrical cell fusion apparatus. The reconstituted embryos were activated after nuclear transfer using St2+. Reconstituted embryos had been produced by the microinjection showed the embryonic development to over 8-cell stages. But, the rate of fragmentation of reconstituted embryos by the microinjection showed a little high rate in comparison with the electrofusion. When some reconstituted embryos by the microinjection were transplanted to pseudopregnant females' oviduct, 9 fetuses were observed at 14 days post coitum.

Animals↗

Complex mechanisms underlying impaired activation of Cdk4 and Cdk2 in replicative senescence: roles of p16, p21, and cyclin D1.

Numerous changes in gene expression are known to occur during replicative senescence, including changes in genes involved in the cell cycle control. In the present study, we have found a severe impairment in the activation of Cdk2 and Cdk4 in response to mitogens in senescent human fibroblasts and determined the molecular basis for this. Although Cdk4 protein was constitutively expressed in senescent cells at the same level as in early-passage young cells, it was found to be complexed with a distinct set of Cdk inhibitors. Cdk4 derived from early passage quiescent cells was effectively activated by incubation with cyclin D1 and Cdk-activating kinase (CAK) in vitro, whereas Cdk4 from senescent cells was not. Cdk2 protein was dramatically decreased in senescent cells and complexed primarily with cyclin D1 and p21. This cyclin D1-bound Cdk2 was not activated by CAK either in vivo or in vitro, implicating cyclin D1 as an inhibitor of Cdk2 activation. Thus, one of the underlying molecular events involved in replicative senescence is the impaired activation of Cdk4 and Cdk2 due to increased binding of p16 to Cdk4 and increased association of Cdk2 with cyclin D1 and p21.

Blood Proteins↗

Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region.

The intensely studied MHC has become the paradigm for understanding the architectural evolution of vertebrate multigene families. The 4-Mb human MHC (also known as the HLA complex) encodes genes critically involved in the immune response, graft rejection, and disease susceptibility. Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F. A total of 127 genes or potentially coding sequences were recognized within the analyzed sequence, establishing a high gene density of one per every 14.1 kb. The identification of 758 microsatellite provides tools for high-resolution mapping of HLA class I-associated disease genes. Most importantly, we establish that the repeated duplication and subsequent diversification of a minimal building block, MIC-HCGIX-3.8-1-P5-HCGIV-HLA class I-HCGII, engendered the present-day MHC. That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA/B genes provides experimental evidence for evolution by "birth and death," which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.

Base Pairing↗

Crystal structure of chitosanase from Bacillus circulans MH-K1 at 1.6-A resolution and its substrate recognition mechanism.

Chitosanase from Bacillus circulans MH-K1 is a 29-kDa extracellular protein composed of 259 amino acids. The crystal structure of chitosanase from B. circulans MH-K1 has been determined by multiwavelength anomalous diffraction method and refined to crystallographic R = 19.2% (R(free) = 23.5%) for the diffraction data at 1.6-A resolution collected by synchrotron radiation. The enzyme has two globular upper and lower domains, which generate the active site cleft for the substrate binding. The overall molecular folding is similar to chitosanase from Streptomyces sp. N174, although there is only 20% identity at the amino acid sequence level between both chitosanases. However, there are three regions in which the topology is remarkably different. In addition, the disulfide bridge between Cys(50) and Cys(124) joins the beta1 strand and the alpha7 helix, which is not conserved among other chitosanases. The orientation of two backbone helices, which connect the two domains, is also different and is responsible for the differences in size and shape of the active site cleft in these two chitosanases. This structural difference in the active site cleft is the reason why the enzymes specifically recognize different substrates and catalyze different types of chitosan degradation.

Amino Acid Sequence↗

The kinesin-related protein, HSET, opposes the activity of Eg5 and cross-links microtubules in the mammalian mitotic spindle.

We have prepared antibodies specific for HSET, the human homologue of the KAR3 family of minus end-directed motors. Immuno-EM with these antibodies indicates that HSET frequently localizes between microtubules within the mammalian metaphase spindle consistent with a microtubule cross-linking function. Microinjection experiments show that HSET activity is essential for meiotic spindle organization in murine oocytes and taxol-induced aster assembly in cultured cells. However, inhibition of HSET did not affect mitotic spindle architecture or function in cultured cells, indicating that centrosomes mask the role of HSET during mitosis. We also show that (acentrosomal) microtubule asters fail to assemble in vitro without HSET activity, but simultaneous inhibition of HSET and Eg5, a plus end-directed motor, redresses the balance of forces acting on microtubules and restores aster organization. In vivo, centrosomes fail to separate and monopolar spindles assemble without Eg5 activity. Simultaneous inhibition of HSET and Eg5 restores centrosome separation and, in some cases, bipolar spindle formation. Thus, through microtubule cross-linking and oppositely oriented motor activity, HSET and Eg5 participate in spindle assembly and promote spindle bipolarity, although the activity of HSET is not essential for spindle assembly and function in cultured cells because of centrosomes.

Fungal Proteins↗