Biomedical subjects
Publications and source records attributed to Takashi Kikuchi.
We show here that La@C72 has a non-IPR cage, unique electronic properties, and high reactivity by the spectroscopic and X-ray crystallographic analysis and the theoretical study. The isolation of La@C72 as a stable derivative might constitute an important stepping-stone on the way to isolation of these unknown metallofullerenes and open new material science of metallofullerenes.
We present experimental results verifying the optical robustness of a 1 x 1 multimode interference (MMI) device that is directly butt coupled with optical fibers at 70 degrees C for 1050 h and discuss the gradual increase of polarization dependent loss. Based on this structure, an electro-optic (EO) MMI waveguide device that can control the output optical power by using an electrode structure located directly on top of the multimode is presented. As a proof of principle, we demonstrate the switching operation of the EO-MMI device using commercially available chromophore as the active EO material.
Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 microg/ml), parathyroid hormone (PTH; 10(-8) M), and bisphosphonates (BPs; 1-25 microM clodronate or 0.1-2.5 microM risedronate) in cultured neonatal calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the alphavbeta3 integrin were found colocalized with the actin ring in the sealing zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in BP-treated cultures showed morphological abnormalities, including retraction of pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and beta3 integrin staining. Depth analyses of calvaria showed that the area of resorbed bone was filled with proliferating osteoblastic cells that stained for alkaline phosphatase, collagen type I, and bone sialoprotein, regardless of the presence of BPs. These studies show that confocal microscopy of neonatal calvaria in culture can be used to assess the cytological relationships between osteoclasts and osteoblastic cells in response to agents that regulate bone remodeling in situ, avoiding systemic effects that can compromise in vivo studies and artifacts associated with studies of isolated osteoclasts.
The first isolation of missing metallofullerene, La@C74, as a derivative is reported. The structural determination has been performed by spectroscopic and, finally, X-ray crystallographic analysis, and the properties of La@C74 are discussed on the basis of the theoretical study.
ConPred II (http://bioinfo.si.hirosaki-u.ac.jp/~ConPred2/) is a server for the prediction of transmembrane (TM) topology [i.e. the number of TM segments (TMSs), TMS positions and N-tail location] based on a consensus approach by combining the results of several proposed methods. The ConPred II system is constructed from ConPred_elite and ConPred_all (previously named ConPred), proposed earlier by our group. The prediction accuracy of ConPred_elite is almost 100%, which is achieved by sacrificing the prediction coverage (20-30%). ConPred_all predicts TM topologies for all the input sequences with accuracies improved by up to 11% over individual proposed methods. In the ConPred II system, the TM topology prediction of input TM protein sequences is executed following a two-step process: (i) input sequences are first run through the ConPred_elite program; (ii) sequences for which ConPred_elite does not give the TM topology are delivered to the ConPred_all program for TM topology prediction. Users can get access to the ConPred II system automatically by submitting sequences to the server. The ConPred II server will return the predicted TM topology models and graphical representations of their contents (hydropathy plots, helical wheel diagrams of predicted TMSs and snake-like diagrams).
In a recent paper, we reported that pravastatin sodium (pravastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme. A reductase, decreases the concentrations of low density lipoprotein (LDL) cholesterol through an LDL receptor pathway in Japanese White (JW) rabbits, whereas this agent lowers high density lipoprotein (HDL) cholesterol in a manner correlated with a reduction of very low density lipoprotein (VLDL) cholesterol secretion from the liver. In the present study, we administered pravastatin to JW rabbits at 30 mg/kg for 14 days and examined further the mechanisms for the reduction of HDL cholesterol. A striking finding was that the 4-day administration of pravastatin at 30 mg/kg selectively decreased the concentration of HDL cholesterol. Since 4-day administration of pravastatin to JW rabbits did not change the concentrations of hepatic LDL receptor proteins, these receptors were not likely to be involved in the reduction of HDL cholesterol. Another important finding was that pravastatin suppressed VLDL cholesteryl ester (CE) secretion from the liver, but not that of other VLDL lipids and VLDL proteins, indicating that the CE-poor VLDL particles were secreted by the consecutive administration of pravastatin. There were, however, no differences in the levels of VLDL cholesterol between the control and pravastatin-treated groups over the experimental period of 14 days. These observations raised the possibility that the reduction of HDL cholesterol in the pravastatin-treated group was due to the transfer of CE molecules from HDL particles to these CE-poor VLDL particles. Molecular species analysis supported this notion that the VLDL-CE in the pravastatin-treated group was rich in cholesteryl linoleate, indicating that the CE in this group mainly originated from HDL, whereas the VLDL-CE in the control group was rich in cholesteryl oleate, indicating that the CE in this group originated from the liver. The present study suggests that pravastatin lowers HDL cholesterol by transferring CE from these lipoproteins to VLDL in JW rabbits.
In experimental animals and humans, the concentration of serum mevalonate (MVA), a direct product of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is considered to reflect the activity of whole-body sterol synthesis. The relationship between the concentration of serum MVA and the activity of sterol synthesis in tissues, however, has not been fully clarified. In the present study, we examined MVA metabolism by using pravastatin, a liver-selective inhibitor of HMG-CoA reductase, and common marmosets, a good model animal for studying lipid metabolism. In the time course study, the maximal reduction in the concentration of serum MVA was observed 2 h after a single oral administration of 30 mg/kg pravastatin to common marmosets. We, therefore, examined the relationship between the concentrations of serum and hepatic MVA, and sterol synthesis in some tissues at this time point. Sterol synthesis was determined ex vivo in tissue slices by measuring the incorporation of [14C]acetate into digitonin-precipitable [14C]sterols. Pravastatin at 0.03-30 mg/kg reduced dose-dependently the activity of hepatic sterol synthesis, whereas no significant reduction of sterol synthesis was observed in other tissues such as intestine, kidney, testis and spleen, even with the highest dose (30 mg/kg). The liver-specific inhibition of sterol synthesis caused parallel reductions in the concentrations of both serum and liver MVA. In addition, there were good correlations between the concentration of either serum or hepatic MVA and the activity of hepatic sterol synthesis. These data indicate that the major origin of serum MVA is the liver, and that the concentration of serum MVA reflects the concentration of hepatic MVA and the activity of hepatic sterol synthesis 2 h after a single oral administration of pravastatin in common marmosets.
An extract from corn germ induced a positive response in the pigeon crop sack test, used for the detection of prolactin-like substances. One of the substances extracted was identified as ferulic acid, which was reported to affect serum gonadotropin levels in ovariectomized male rats. To evaluate the effects of ferulic acid on bone loss, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were given ferulic acid and/or 17a-ethynylestradiol daily for 8 weeks, and serum hormone levels and tibial bone mineral density were measured. In metaphysis of the tibia, which was abundant in cancellous bone and more reflective of BMD than whole tibia, the BMD was markedly reduced by ovariectomy and enhanced by the treatment with estrogen or ferulic acid in the ovariectomized rats. The treatment slightly increased the serum levels of estrogen and progesterone and alkaline phosphatase activity, which was reduced by estrogentreatment, i.e. the mechanism of bone formation by ferulic acid was suggested to be different from that by estrogens. These results indicate that ferulic acid promotes bone remodeling, leading to a predominantly osteoblastic phase, besides bone resorption by osteoclasts.