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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 73 records · Page 4Linked to original sources
PubMed1999

Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism.

A mouse model of Rubinstein-Taybi syndrome (RTS) was generated by an insertional mutation into the cyclic AMP response element-binding protein (CREB)-binding protein (CBP) gene. Heterozygous CBP-deficient mice, which had truncated CBP protein (residues 1-1084) containing the CREB-binding domain (residues 462-661), showed clinical features of RTS, such as growth retardation (100%), retarded osseous maturation (100%), hypoplastic maxilla with narrow palate (100%), cardiac anomalies (15%) and skeletal abnormalities (7%). Truncated CBP is considered to have been acting during development as a dominant-negative inhibitor to lead to the phenotypes of RTS in mice. Our studies with step-through-type passive avoidance tests and with fear conditioning test showed that mice were deficient in long-term memory (LTM). In contrast, short-term memory (STM) appeared to be normal. These results implicate a crucial role for CBP in mammalian LTM. Our CBP +/- mice would be an excellent model for the study of the role of CBP in development and memory storage mechanisms.

Animals↗
PubMed1999

A patient with genetic deletion of glutathione-S-transferase T1 and M1 who developed non-small-cell lung cancer and myelodysplastic syndromes.

Glutathione S-transferase (GST) M1 polymorphism is a marker for susceptibility to smoking-related neoplasms, such as lung and bladder cancer. Recently, a genetic deletion of GSTT1, an isoenzyme of GST, has been reported to be associated with myelodysplastic syndromes (MDS). A 59-year-old man with a long-term smoking habit was treated successfully for non-small-cell lung cancer. Four years after the surgical removal of his lung cancer, he developed MDS and died. Using a polymerase chain reaction-based genotyping method, he was found to have a deletion of both the GSTM1 and GSTT1 genes. Screening for the deletion of the GSTM1 and GSTT1 genes may be useful for assessing individual genetic susceptibility to smoking-related lung cancer and MDS.

Asian People↗
PubMed1999

Prophylaxis of local vascular graft infection with levofloxacin incorporated into albumin-sealed dacron graft (LVFX-ALB Graft).

An animal model was used to assess the efficacy of levofloxacin (LVFX) incorporated into albumin (ALB)-sealed Dacron (LVFX-ALB) graft for the prevention of vascular graft infections caused by Staphylococcus aureus. Under general anesthetic, an interposition graft was placed into dog carotid artery. On completion of the operation, 0.1 ml of normal saline containing 10(7) colony-forming units (CFU) of a slime-producing S. aureus was inoculated directly onto the graft. After 1 day, the samples were sterilely harvested. The antibacterial activity of LVFX into the LVFX-ALB graft was evaluated by colony counting in bacterial cultures and by the fluorescent antibody method staining bacteria adhesion to the grafts. LVFX-ALB grafts had a lower infection rate than the control grafts (1/4, 10(2) CFU vs 4/4, 1.50 x 10(5)+/-1.38 x 10(5)CFU (mean+/-SE)). In an immunostaining study, LVFX-ALB grafts had small fluorescent areas showing S. aureus adhesion, while fluorescence was observed over the entire surface of the control grafts. Therefore, LVFX-ALB presumably had a bactericidal action and adhesive prevention against inoculated S. aureus. LVFX-ALB may be useful in preventing graft infections during and immediately after vascular reconstruction.

Albumins↗
PubMed1999

Characterization of ocular pharmacokinetics of tilisolol after instillation into anesthetized rabbits.

The purpose of this study was to characterize the ocular pharmacokinetics of a beta-blocker, tilisolol, after instillation into anesthetized rabbits using a mathematical model including a diffusion process. The samples were analyzed by HPLC. Anesthetized rabbit was used as a model of tear secretion deficiency. Anesthetized rabbits showed higher drug concentration in the tear fluid and aqueous humor after instillation than unanesthetized rabbits. A mathematical model including a diffusion process and in vivo penetration parameters well described the concentrations of tilisolol in the aqueous humor after instillation in anesthetized rabbits.

Administration, Topical↗
PubMed1999

The effects of tone exposure on the inner ear functions in the guinea pig: impact tone vs. steady state tone.

The damage-risk criterion (DRC) for hearing supposes that sound exposure with equal energy implies equal risk for noise-induced hearing loss (NIHL). We measured cochlear microphonics (CM), compound action potential (CAP), endocochlear potential (EP) and K+ ion concentration in the scala media, to see if the same level of Leq24h (impact tone and steady state tone) induced the same physiological changes in the inner ear function or not. Regarding the equal energy principle (EEP), we also examined if the EEP is appropriate or not at exposure of moderate level tone. We also checked how the time interval between impact tones affects or not the inner ear functions at the same Leq24h tone exposure. Therefore we used exposure at 1 pulse/second or 1 pulse/3 seconds and steady state tone exposure at Leq24h=90, 85 and 80 dB. The results are the following. Both steady state and impact tone exposure causes change of the electrophysiological data. First, CM maximum output voltage after exposure to impact tone of 115 dB (Leq24h=90 dB) was lower than after exposure to a 8 kHz steady state tone of 90 dB. CAP threshold (below 10 microV) obtained after the 115 and 110 dB exposure of impact tone were 5-10 dB higher than that of steady state tone of 90 dB. The negative EP induced by impact tone exposures showed the same tendency as the CM experiments. Having more frequent pulses (1 pulse/second vs. to 1 pulse/3 seconds) showed more inhibition. The K+ concentration time course remained similar to the control when the Leq24h was low (80 dB). Impact tone exposure induced stronger effects to the inner ear at exposure of moderate level tone than that of steady state tone of Leq24h.

Acoustic Stimulation↗
PubMed1999

Comparative study of effects of impact tone and steady state tone exposure: EP and concentration of K+ ion and Na+ ion.

To test the adequacy of equal energy principle (EEP), guinea pigs were exposed to impact tone. The changes in electrophysiological data, namely endocochlear potential (EP) and the change in K+ ion and Na+ ion concentrations in the endolymph were investigated. The frequency of impact tone was 1 pulse/second or 1 pulse/3 seconds. The steady state tone had Leq24h = 100, 95, 90 or 85 dB, and impact tone had Leq24h = 95, 90 or 85 dB. The results are the following. Both steady state and impact tone exposure cause changes of electrophysiological data. The effects on the absolute value of negative EP induced by impact tone exposures were smaller than that of steady state tone of the same Leq. The rate of pulses was also an important factor for impact tone exposure. Impact tone exposure of 1 pulse/second caused smaller absolute value of negative EP than that of 1 pulse/3 seconds. The K+ ion concentration time course in the endolymph remained similar to the control (Exp. 1) only in Exp. 8 (85 dB; the lowest steady state noise exposure in our experiments), but no decrease in the K+ ion concentration was detected in the other experiments, suggesting an alteration in the K+ ion flow. The Na+ ion concentration time course was also influenced showing no increase in Na+ ion concentration compared to the control (Exp. 1c) and the lowest steady-state exposure experiment (Exp. 8c). Our experimental results suggest that both the K+ ion and Na+ ion movement are altered by tone exposure. We found also that the different types of noise exposure with the same Leq value does not exhibit the same changes. Leq24h is not an accurate damage risk criteria.

Acoustic Stimulation↗
PubMed1999

The mouse interferon-gamma transgene chronic hepatitis model (Review).

Acute hepatitis models are widely used for the evaluation of drugs for liver disease or for basic research on hepatitis. However, it is difficult to produce similar liver conditions to human chronic hepatitis with an acute hepatitis model. The interferon-gamma (IFN-gamma) transgenic mouse, which carries the mouse IFN-gamma gene, strongly expresses the IFN-gamma gene in the liver and develops chronic hepatitis from the age of 6-10 weeks. We found that the hepatitis in this mouse reflects human chronic hepatitis at least in the following points, i) infiltration by lymphoid cells into the portal areas and necroinflammation in the lobules, and ii) expression of Fas antigen and Fas ligand mRNAs in the liver. Furthermore, the induction of CPP32-like protease activity in the transgenic mouse liver suggests the involvement of this protease activity in the development of chronic hepatitis.

Animals↗
PubMed1999

Long lasting chronic hepatitis is accompanied by cyclin D1 gene expression in the mouse.

The interferon-gamma (IFN-gamma) transgenic mouse expresses the IFN-gamma gene strongly in the liver and develops chronic hepatitis from 6-10 weeks of age. Previously we reported the detection of hepatocyte apoptosis and the expression of the Fas system in the transgenic mouse liver. The objective of the present study was to examine the possible development of favorable conditions for predisposing cells to malignancy. The connection between the cell cycle and cancer has become evident, and the relation of cyclin D1 (CD1) with hepatocellular carcinomas has been strengthened. In the liver of transgenic mice of 48 weeks of age, c-myc and CD1 gene expression was induced, indicating progression of the cell cycles. p21 gene expression in the transgenic mouse liver might counteract cell-cycle progression promoted by c-myc and CD1. In the liver of 8-week-old transgenic mice, expression of c-myc mRNA was correlated with the levels of plasma transaminase activities. In these 8-week-old transgenic mice, however, CD1 mRNA was not induced, regardless of the progression of hepatitis. Based on these results, we conclude that long lasting hepatitis may lead to favorable conditions for predisposing cells to malignancy.

Animals↗
PubMed1999

Enhancement of ocular drug penetration.

Although new drugs have recently been developed within the field of ophthalmology, the eye's various defense mechanisms make it difficult to achieve an effective concentration of these drugs within the eye. Drugs administered systemically have poor access to the inside of the eye because of the blood-aqueous and blood-retinal barriers. And although topical instillation of drugs is very popular in ophthalmology, topically applied drugs are rapidly eliminated from the precorneal area. In addition, the cornea, considered a major pathway for ocular penetration of topically applied drugs, is an effective barrier to drug penetration, since the corneal epithelium has annular tight junctions (zonula occludens), which completely surround and effectively seal the superficial epithelial cells. Various drug-delivery systems have been developed to increase the topical bioavailability of ophthalmic drugs by enhancement of the ocular drug penetration. The first approach is to modify the physicochemical property of drugs by chemical and pharmaceutical means. An optimum promoiety can be covalently bound to a drug molecule to obtain a prodrug that can chemically or enzymatically be converted to the active parent drug, either within the cornea or after the corneal penetration. Along these same lines, the transient formation of a lipophilic ion pair by ionic bonding is also useful for improving ocular drug penetration. The second approach is to modify the integrity of the corneal epithelium transiently by coadministration of an amphiphilic substance or by chelating agents that act as drug-penetration enhancers. The third approach modifies the integrity of the corneal epithelium transiently by physical techniques including iontophoresis and phonophoresis. This paper reviews the absorption behavior and ocular membranes penetration of topically applied drugs, and the various approaches for enhancement of ocular drug penetration in the eye.

Drug Carriers↗
PubMed1999

[Experimental study of water leakage in duraplasty using ePTFE sheet as an artificial dura mater].

The authors have evaluated the preventive effect of water leakage from the suture holes of expanded polytetrafluoroethylene (ePTFE) sheet. Six currently available suture materials (4-0 SURGILON, 4 types of Gore-tex suture, DuraClose) were compared. The water leakage was 0.05 cc/min when using Gore-tex suture (CV-6, needle/thread ratio = 1.0), 0.025 cc/min when using DuraClose. With each two material, the water leakage was significantly less (p < 0.05) in comparison with other materials. Scanning electron microscopic examination revealed that the residual suture holes were minimum when using Gore-tex suture (CV-6, needle/thread ratio = 1.0). In conclusion, running suture with Gore-tex suture (CV-6, needle/thread ratio = 1.0) could be effective in preventing water leakage from the suture holes of ePTFE sheet in duraplasty.

Dura Mater↗
PubMed1999

Exchangeable gene trap using the Cre/mutated lox system.

The gene trap technique is a powerful approach for characterizing and mutating genes involved in mouse development. However, one shortcoming of gene trapping is the relative inability to induce subtle mutations. This problem can be overcome by introducing a knock-in system into the gene trap strategy. Here, we have constructed a new gene trap vector, pU-Hachi, employing the Cre-mutated lox system (Araki et al., 1997), in which a pair of mutant lox, lox71 and lox66, was used to promote targeted integrative reaction by Cre recombinase. The pU-Hachi carries splicing acceptor (SA)-lox71-internal ribosomal entry site (IRES)-beta-geo-pA-loxP-pA-pUC. By using this vector, we can carry out random insertional mutagenesis as the first step, and then we can replace the beta-geo gene with any gene of interest through Cre-mediated integration. We have isolated 109 trap clones electroporated with pU-Hachi, and analyzed their integration patterns by Southern blotting to select those carrying a single copy of the trap vector. By use of some of these clones, we have succeeded in exchanging the reporter gene at high efficiency, ranging between 20-80%. This integration system is also quite useful for plasmid rescue to recover flanking genomic sequences, because a plasmid vector sequence can be introduced even when the pUC sequence of the trap vector is lost through integration into the genome. Thus, this method, termed exchangeable gene trapping, has many advantages as the trapped clones can be utilized to express genes with any type of mutation.

Animals↗
PubMed1998

Functional dissection of the cytoplasmic subregions of the IL-2 receptor betac chain in primary lymphocyte populations.

The interleukin 2 (IL-2) receptor betac chain (IL-2Rbetac) is known to regulate the development and function of distinct lymphocyte populations. Thus far, the functions of the IL-2Rbetac cytoplasmic subregions have been studied extensively by using cultured cell lines; however, this approach has limitations with respect to their functions in distinct primary lymphocyte populations. In the present study, we generated mice each expressing a mutant form of an IL-2Rbetac transgene, lacking the cytoplasmic A- or H-region, on an IL-2Rbetac null background. We show that lack of the H-region, which mediates activation of the Stat5/Stat3 transcription factors, selectively affects the development of natural killer cells and T cells bearing the gamma delta T cell receptor. This region is also required for the IL-2-induced proliferation of T cells in vitro, by upregulating IL-2Ralpha expression. In contrast, the A-region, which mediates activation of the Src family protein tyrosine kinase (PTK) members, contributes to downregulation of the T cell proliferation function. The IL-2Rbetac null mutant mice develop severe autoimmune symptoms; these are all suppressed following the expression of either of the mutants, suggesting that neither the Stats nor the Src PTK members are required. Thus, our present approach offers new insights into the functions of these cytoplasmic subregions of the IL-2Rbetac chain.

Animals↗
PubMed1998

Effects of food consistency on the modulatory mode of the digastric reflex during chewing in freely behaving rabbits.

Effects of food consistency on the mode of the phase-linked modulation in the digastric reflex amplitude were examined in naturally chewing rabbits. Two test foods with different textures (bread as a soft food, pellet as a hard food) were used. The digastric reflex was elicited by electrical stimulation (10 train pulses at 2 kHz) of the inferior alveolar nerve. The amplitude of the digastric reflex measured was divided into three categories depending on the chewing phases in which the stimulus was delivered and each value was compared with the control response obtained when the animal was resting. The reflex was strongly inhibited in the jaw-opening phase and no difference was observed in the inhibitory effect between the foods. In the jaw-closing phase, larger digastric reflexes than those in the opening phase were elicited with both foods. This was the case in both the fast-closing and slow-closing phases. Reflex amplitude was significantly larger during chewing of the hard food than the soft food and, thereafter, inhibition of the reflex was observed only during chewing of the soft food in the closing phase. The results suggest the following: (1) food consistency may affect the central mechanism which regulates the digastric reflex and (2) the reflex may contribute to the regulation of masticatory force during chewing particularly hard food.

Animal Feed↗