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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 37 records · Page 2Linked to original sources
PubMed2001

Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein.

BACKGROUND: It is well documented that serum insulin-like growth factor 1 (IGF-1) levels as well as growth hormone secretion decline with advancing age. Low levels of IGF-1 are shown to be associated with low activity of growth hormone, low lean mass, and high body fat mass; however, in the elderly, the relationship has not been confirmed. METHODS: We studied serum IGF-1 levels in 49 centenarians, who are at the ultimate stage of physiological senescence, and investigated the possible relationship between IGF-1 and body mass index, lipid parameters, nutritional indices, physical and cognitive function, and frequency of hip fracture. As nutritional indices, serum levels of albumin, prealbumin, transferrin, and retinol binding protein were measured. Cognitive function of the centenarians was assessed by clinical dementia rating. RESULTS: In the centenarians, the mean levels of IGF-1 were relatively low, indicating that there is an age-associated decline in IGF-1 even in the extremely old age. We demonstrated a strong association of IGF-1 with prealbumin and retinol binding protein (r2 = .192, .195, respectively); however, there was no association with albumin, transferrin, or body mass index. Interestingly, centenarians with lower IGF-1 levels had a higher prevalence of definitive dementia. CONCLUSIONS: These data suggest that serum IGF-1 levels in the centenarians appeared to reflect their short-term nutritional status as a rapid turnover protein. It is also suggested that low levels of serum IGF-1 may be involved in the progression of dementia in the oldest old.

Aged↗
PubMed2001

Strain-dependency of chromosomal abnormalities in lymphomas developed in E mu-myc transgenic mice.

We previously showed that B and T cell lymphoma development in Em (immunoglobulin heavy chain enhancer)-myc transgenic mice is dependent on the mouse strain. To determine whether any non-random chromosomal abnormality that was present was caused by variations in the lymphoma cell type or by a different genetic background, we crossed C3H transgenic mice with other inbred strains of mice, C57BL / 6 or BALB / c. Cytogenetic analysis showed a high frequency of non-random chromosomal aberrations, namely, duplication or amplification of part of chromosome 5 containing the transgene and trisomy of chromosome 1, 6, or 12 in the genetic background of C3H x C57BL / 6 mouse and C3H x BALB / c mouse, respectively, regardless of cell type of lymphoma. These results suggest that non-random chromosomal abnormalities in lymphoma cells are dependent on the genetic background of mouse, not on the tumor cell type in Em-myc transgenic mouse.

Animals↗
PubMed2001

Sustained ocular delivery of tilisolol to rabbits after topical administration or intravitreal injection of lipophilic prodrug incorporated in liposomes.

To improve the retention time of tilisolol in the precorneal area or vitreous body, we prepared liposomes incorporating the O-palmitoyl prodrug of tilisolol. O-Palmitoyl tilisolol was completely incorporated in the liposomes. After topical administration of O-palmitoyl tilisolol liposomes to the rabbit eye, O-palmitoyl tilisolol rapidly disappeared from the tear fluid. The inclusion of 2% carmellose sodium slightly prolonged the retention of O-palmitoyl tilisolol in the tear fluid. After intravitreal injection of O-palmitoyl tilisolol liposomes, there was a relatively prolonged retention of O-palmitoyl tilisolol in the vitreous body. At 24 and 48 h after intravitreal injection of O-palmitoyl tilisolol liposomes, the tilisolol concentration in the vitreous body was significantly higher compared with the concentration after intravitreal injection of tilisolol liposomes.

Administration, Topical↗
PubMed2001

Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17beta-oestradiol.

Aromatase P450 (CYP19) is an enzyme catalysing the conversion of androgens into oestrogens. We generated mice lacking aromatase activity (ArKO) by targeted disruption of Cyp19 and report the characteristic features of the ArKO ovaries and uteri as revealed by histological and biochemical analyses. ArKO females were totally infertile but there were as many developing follicles in their ovaries at 8 weeks of age as in wild-type ovaries. Nevertheless, no typical corpus luteum was observed in the ArKO ovaries. Electron microscopy revealed the presence of well-developed smooth endoplasmic reticulum, few lipid droplets and mitochondria with less organized tubular structures in the ArKO luteinized interstitial cells. These ultrastructural features were different from those of the wild-type interstitial cells, where there are many lipid droplets and mitochondria with well-developed tubular structures, characteristic of steroid-producing cells. When ArKO mice were supplemented with 17beta-oestradiol (E(2); 15 microg/mouse) every fourth day from 4 weeks of age for 1 month, increased numbers of follicles were observed in the ovaries as compared with those of untreated ArKO mice, although no typical corpus luteum was detectable. Ultrastructural analysis revealed the disappearance of the accumulated smooth endoplasmic reticulum in the luteinized interstitial cells after E(2 )supplementation. Transcripts of pro-apoptotic genes such as p53 and Bax genes were markedly elevated in the ArKO ovaries as compared with those of wild-type mice. Although E(2) supplementation did not cause suppression of the elevated expression of p53 and Bax mRNAs, it caused marked enhancement of expression levels of lactoferrin and progesterone receptor mRNAs in the uteri as well as increases in uterine wet weight. At 8 months of age, ArKO mice developed haemorrhages in the ovaries, in which follicles were nearly depleted, while age-matched wild-type females still had many ovarian follicles. Furthermore, macrophage-like cells were occasionally observed in the ArKO ovarian follicles. These results suggested that targeted disruption of Cyp19 caused anovulation and precocious depletion of ovarian follicles. Additionally, analysis of mice supplemented with E(2) demonstrated that E(2) apparently supports development of ovarian follicles, although it did not restore the defect in ovulation.

Animals↗
PubMed2001

[Suggestions from a centenarian study--aging and inflammation].

With the numbers of elderly increasing rapidly, it is important for both individuals and society that the oldest old maintains autonomy. To know how to attain successful aging, we investigate the status of centenarians. The characteristics of centenarians in Tokyo is 1) low level of nutritional parameters, 2) low level of cholesterol and HDL-cholesterol, 3) low level of red blood cells and hemoglobin, 4) high level of CRP, 5) high level of homocysteine, 6) high level of von Willbrand factor. The incidence of dementia is 59.3%. Are these characteristics due to aging itself or other factors? We examined the effect of nutritional status, inflammation and level of homocysteine on the characteristics. The level of albumin is associated with serum level of lipid, RBC, ADL and cognitive function. The level of CRP is related to the level of albumin, suggesting that inflammation is related to nutritional status. The level of homocysteine is associated with the level of von Willbrand factor, suggesting that homocysteine is related to endothelial injury. From these data, we propose the hypothesis that proinflammatory status is associated with aging, resulting in a part of characteristics of centenarians. Homocysteine is partly responsible for endothelial injury. Intervention to suppress proinflammatory status and homocysteine level may promote QOL in the oldest old.

Aged↗
PubMed2000

Head movements and neck muscle activities associated with the jaw movement during mastication in the rabbit authors.

Rhythmical head movements and neck muscle activities associated with the masticatory jaw movement were investigated in rabbits. In natural mastication, head movements and neck muscle activities showed a rhythmical feature synchronized with jaw movement. During cortically induced rhythmical jaw movements, some neck muscle showed rhythmical activity induced by biting a wooden stick. Neck muscles may contribute to the rhythmical head movement after loading the tooth with food.

Animals↗
PubMed2000

An auxiliary mode of apoptotic DNA fragmentation provided by phagocytes.

CAD (caspase-activated DNase) can cause DNA fragmentation in apoptotic cells. Transgenic mice that ubiquitously express a caspase-resistant form of the CAD inhibitor (ICAD) were generated. Thymocytes prepared from the mice were resistant to DNA fragmentation induced by a variety of stimuli. However, similar numbers of TUNEL-positive cells were present in adult tissues of transgenic and wild-type mice. Exposure to gamma-irradiation caused a striking increase in the number of TUNEL-positive cells in the thymus of wild-type, but not transgenic, mice. TUNEL-positive nuclei in transgenic mice were confined to thymic macrophages. When apoptotic thymocytes from the transgenic mice were cocultured with macrophages, the thymocytes underwent phagocytosis and their chromosomal DNA underwent fragmentation. This DNA fragmentation was sensitive to inhibitors that block the acidification of lysosomes. Hence, we conclude that the DNA fragmentation that occurs during apoptosis not only can result cell-autonomously from CAD activity but can also be attributed to a lysosomal acid DNase(s), most likely DNase II, after the apoptotic cells are engulfed.

Animals↗
PubMed2000

Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination.

The mechanisms underlying oligodendrocyte (OLG) loss and the precise roles played by OLG death in human demyelinating diseases such as multiple sclerosis (MS), and in the rodent model of MS, experimental autoimmune encephalomyelitis (EAE), remain to be elucidated. To clarify the involvement of OLG death in EAE, we have generated transgenic mice that express the baculovirus anti-apoptotic protein p35 in OLGs through the Cre-loxP system. OLGs from cre/p35 transgenic mice were resistant to tumor necrosis factor-alpha-, anti-Fas antibody- and interferon-gamma-induced cell death. cre/p35 transgenic mice were resistant to EAE induction by immunization with the myelin oligodendrocyte glycoprotein. The numbers of infiltrating T cells and macrophages/microglia in the EAE lesions were significantly reduced, as were the numbers of apoptotic OLGs expressing the activated form of caspase-3. Thus, inhibition of apoptosis in OLGs by p35 expression alleviated the severity of the neurological manifestations observed in autoimmune demyelinating diseases.

Animals↗
PubMed2000

Distribution and serum concentration of sisomicin released from fibrin glue-sealed dacron graft in the rat and human.

We investigated whether or not fibrin glue (FG) used as a sealant in vascular prostheses to prevent leakage might be useful as a carrier of antibiotics for the prevention of local graft infection. Sisomicin (SISO) was incorporated into fibrin glue (SISO-FG) and evaluated as to its safety and pharmacokinetics. SISO (1.75 mg) -FG Dacron grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, and then the changes in SISO concentrations in the serum and in the tissue around the implantation sites were compared with those same sites in rats that had had intravenous injection of SISO (1.75 mg). The serum SISO concentrations were significantly lower in the SISO-FG Dacron graft group than they were in the intravenous injection group. However, until 4 h after implantation the SISO concentrations in the tissues around the implantation sites were significantly higher in the SISO-FG Dacron group than they were in the iv injection group, and the peak concentrations during that time were 5.8 times higher for the SISO-FG Dacron group than they were for the intravenous injection group. The ratio of the area under the tissue concentration time curve of SISO (AUC tissue) after implantation of the SISO-FG Dacron graft to that after intravenous injection of SISO was 13.08. Therefore, FG was considered to control the release of SISO into the serum and to maintain a high SISO concentration in the tissue around the implantation site. Clinically, SISO (45 mg) -FG was applied directly to the Dacron grafts implanted in 10 patients who underwent prosthetic vascular reconstruction. No graft infection was observed in any of the patients who received SISO-FG Dacron grafts. The mean serum concentration of SISO was 0.65+/-0.17 microg/mL after 1 h and 0.33+/- 0.21 microg/mL after 3 h. The results of these clinical applications are in close correlation with those of the animal experiment and suggest that FG is useful as a carrier of SISO, allowing its controlled release for the prevention of local infection.

Aged↗
PubMed2000

Delayed infection of a lymphocele following mastectomy with immediate breast reconstruction: report of a case.

We report herein a rare case of delayed infection of a lymphocele following mastectomy with immediate breast reconstruction. A 38-year-old woman presented to our hospital 7 months after undergoing a left-modified radical mastectomy with an immediate breast reconstruction, following the sudden development of a giant mass in the left thoracoabdominal region as well as a high fever and shivering. Ultrasonography and a computed tomographic scan revealed massive fluid retention extending from the left axilla to the lower abdominal region. Puncture drainage was performed three times and the injection of an antibiotic directly into the cyst resulted in resolution of the fluid. This massive retraction of fluid was considered to have resulted from a delayed infection of an axillary lymphocele.

Adenocarcinoma↗
PubMed2000

Maximizing yellow pigment production in fed-batch culture of Monascus sp.

Yellow pigment production in exponential fed-batch cultivation of Monascus sp. was studied. Due to the difficulty of measuring the optical density for accurate determination of the cell concentration, a capacitance probe was employed on-line. The feed rate needed to keep the specific growth rate, mu, constant in fed-batch culture was determined on the basis of the cell concentration measured by the capacitance probe. Control of mu was improved by using updated information on the cell concentration compared with the simple feed-forward determination method using the initial cell concentration only. The highest specific pigment production rate was achieved with a mu of 0.02 h(-1) in the feeding phase. However, among several fermentation examined, the largest pigment production in the final step was obtained at a mu of 0.01 h(-1); in each case the same amount of substrates was used. An investigation of the optimal initial glucose concentration revealed that pigment production was maximum when the initial glucose concentration in the batch mode was 10 g/l and mu was 0.01 h(-1) in the fed-batch mode. It was also found that the pellet weight in the fermentation could be accurately estimated by image analysis. The ratio of the mycelium weight to the total cell weight estimated from information on the total cell weight and the estimated pellet weight was found to be more than 80%. However, no clear quantitative relationship could be discerned between the specific pigment production rate, rho, and the ratio of mycelium in the cell population.

Journal Article↗
PubMed2000

An innovative application of anatomic electromagnetic voltage mapping in a patient with Ebstein's anomaly undergoing permanent pacemaker implantation.

A novel application of the Biosense CARTO System anatomic electromagnetic voltage mapping is presented, utilized as a guide for permanent pacemaker placement. The technique is illustrated in the successful implantation of an atrial lead in a patient with Ebstein's anomaly characterized by a severely dilated right atrium and extremely low-amplitude voltage signals, requiring a DDD pacemaker. Electromagnetic voltage mapping can be used in selected patients with structural heart disease to determine the optimal site for permanent pacemaker lead placement.

Adult↗
PubMed2000

Pharmacokinetic prediction of the ocular absorption of an instilled drug with ophthalmic viscous vehicle.

We previously developed an in vivo pharmacokinetic model that accounts for the corneal diffusion in albino rabbits and predicts the concentration of beta-blockers in the anterior segments. The purpose of this study is to pharmacokinetically predict the ocular absorption and characterize the systemic absorption of instilled drug with ophthalmic viscous vehicle to assist in its design and evaluation. Tilisolol and carboxymethylcellulose sodium salt (CMC) were used as the model ophthalmic drug and viscous polymer, respectively. After instillation of tilisolol with CMC vehicle in rabbits, the disposition of the drug in tear fluid, aqueous humor, and plasma were determined by HPLC. The ocular and systemic absorption were analyzed by a mathematical model including a diffusion process and a two-compartment model with first-order absorption, respectively. CMC vehicle increased the area under the concentration-time curve (AUC) of tilisolol in the tear fluid and aqueous humor and slightly reduced the AUC in plasma. The concentrations of tilisolol in the aqueous humor after instillation with CMC vehicle were accurately predicted from the tear concentrations by using the in vivo ocular pharmacokinetic model. CMC vehicle improved the ocular delivery of tilisolol.

Absorption↗
PubMed2000

Modification of ocular permeability of peptide drugs by absorption promoters.

The purpose of this study was to investigate the effect of absorption promoters on the ocular membrane permeability of thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) as model peptides. The permeabilities of TRH and LHRH were measured using a two-chamber glass diffusion cell mounted with isolated ocular membranes of albino rabbits. Saponin, EDTA, benzalkonium chloride and paraben were used as absorption promoters. These promoters enhanced the permeability of hydrophilic molecules through the cornea and conjunctiva. The promoting effects of the absorption promoters on the conjunctival drug penetrations were not as strong as those on the corneal penetrations. The different responses of the corneal and conjunctival drug penetrations to these promoters may be useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled drugs. The promotional effects of absorption promoters on the corneal drug penetration apparently increased with an increase in penetrant molecular weights, although those on the conjunctival drug penetrations did not depend on the molecular weights.

Absorption↗
PubMed2000

Expression of cyclooxygenase mRNA in the livers of mice with interferon-gamma chronic hepatitis.

Interferon-gamma (IFN-gamma) transgenic mice expressed the IFN-gamma gene in the liver and developed chronic hepatitis. The expression of cyclooxygenase (Cox)-1 and -2 mRNA were studied in the livers of these mice. A faint band of Cox-1 mRNA was observed in the livers of both normal and transgenic mice. Slight expression of Cox-2 mRNA was observed in the normal mouse liver, and this mRNA expression was induced in the transgenic mouse liver. The present results showed the induction of Cox-2 mRNA expression in the livers of transgenic mice with chronic hepatitis.

Animals↗
PubMed2000

Identification of somatotrophs, mammosomatotrophs, and mammotrophs by sandwich cell immunoblot assay in GH-secreting adenomas and prolactinomas: correlations between the proportions of hormone secreting cells and tumor size.

Sandwich cell immunoblot assay(sandwich CIBA) was used to identify somatotrophs (GH cells), mammosomatotrophs, and mammotrophs (PRL cells) in pituitary tumors obtained from patients with GH-secreting adenomas and prolactinomas. The mean serum GH level was 177.6 ng/ml in 19 patients with GH-secreting adenomas and the mean PRL level was 2,129 ng/ml in 9 patients with prolactinomas. GH-secreting adenomas could be divided into 3 groups according to the proportions of the cell types. The GH cell dominant type had more than 70% GH cells. The mammosomatotroph cell dominant type had more than 80% mammosomatotrophs. The non-dominant type had no dominant cell type. There was a good correlation (r2=0.804) between serum GH levels and tumor size in patients with the GH cell dominant type (n=10). The nondominant type (n=8) had a low serum level of GH except for one tumor. The mammosomatotroph cell dominant type (n=1) showed high serum levels of both GH and PRL. All prolactinomas had a predominance of PRL cells. Sandwich CIBA is a simple method for detecting GH cells, mammosomatotrophs, and PRL cells, and useful for classification for GH-secreting adenomas.

Adenoma↗