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T Tsunenari

Publications and source records attributed to T Tsunenari.

At least 19 recordsLinked to original sources
PubMed2001

Physiology of morphologically identified cells of the bullfrog fungiform papilla.

Voltage-gated ionic current and the response to quinine were studied on the four types of morphologically identified taste cells of the bullfrog fungiform papilla by whole-cell patch clamp recording with a Lucifer yellow-filled pipette. Dye-coupled type Ia cells (mucous cells) did not show voltage-activated currents. Type Ib cells (wing cells) characterized by the fin-like processes, type II cells (rod cells) having a thick straight dendrite running to the surface and type III cells with a thin dendrite had voltage-gated sodium (INa) and potassium currents (IK) and generated action potentials. The amplitude of INa was significantly larger in type Ib and II cells than in type III cells. Type Ib and II cells responded to quinine but Type III cells did not.

Action Potentials↗
PubMed2001

Effect of extracellular Ca2+ on the quinine-activated current of bullfrog taste receptor cells.

The bitter substance quinine activates a cation current from the frog taste receptor cell. We have analysed the noise associated with this current, and the effect of extracellular Ca2+ on the current, using whole-cell recording on single dissociated cells. Quinine induced an inward current from the taste receptor cell near the resting potential. The response was accompanied by an increase in current fluctuations. From the variance/mean ratio of the quinine-activated current, the single-channel conductance was estimated to be 12 pS in the nominal absence of extracellular Ca2+. In the presence of 1.8 mM Ca2+, this conductance decreased to 5 pS. These values broadly agree with those previously obtained from excised, outside-out membrane patches. The dependence of the current on quinine concentration had a K1/2 of 0.48 mM in the absence of extracellular Ca2+, consistent with measurements from excised patches. The K1/2 value increased to 2.8 mM in 1.8 mM external Ca2+. The maximum current induced by quinine was also reduced by about 20% by Ca2+. The spectral power density distribution of the quinine-activated current could be described by the sum of two Lorentzian functions, with corner frequencies not substantially different in the absence and presence of 1.8 mM external Ca2+. The above results lend further support to the notion that the major component of the response of frog taste receptor cells to quinine comes from an ion channel directly activated by quinine.

Animals↗
PubMed1999

Activation by bitter substances of a cationic channel in membrane patches excised from the bullfrog taste receptor cell.

1. The response to bitter-tasting substances was recorded in outside-out membrane patches excised from the taste receptor cell of the bullfrog fungiform papilla. 2. Application of a bitter-tasting substance, quinine or denatonium, induced channel openings under conditions in which none of the second messenger candidates or their precursors (e.g. cyclic nucleotide, inositol 1,4,5-trisphosphate, Ca2+, ATP and GTP) were present on either side of the membrane. The response could be recorded > 10 min after excision of the patch membrane. These data suggest that the channel was directly gated by the bitter-tasting substances. 3. No change in response was detected upon addition to the cytoplasmic side of either GDPbetaS (1 mM) or GTPgammaS (1 mM), suggesting that the G protein cascade has no direct relation to response generation. 4. The quinine-induced current was dose dependent. The lowest effective concentration was approximately 0.1 mM, and the saturating concentration was near 1 mM. The dose-response curve was fitted by the Hill equation with a K of 0.52 mM and a Hill coefficient of 3.8. 5. The single channel conductance measured in 120 mM NaCl solution was 10 pS. The channel was cation selective, and the ratio of the permeabilities for Na+, K+ and Cs+ (PNa : PK : PCs) was 1 : 0.48 : 0.39. The unitary conductance was dependent on the extracellular Ca2+ concentration ([Ca2+]o); 9.2 pS in a nominally Ca2+-free solution, and 4.5 pS in 1. 8 mM [Ca2+]o. 6. The dose dependence, the ion selectivity and the dependence of the unitary conductance on [Ca2+]o were almost identical to those of the quinine-induced whole-cell current reported previously, indicating that the channel activity observed in the excised membrane is the basis of the whole-cell current. 7. The present observations suggest the new possibility that the cationic channel directly gated by bitter substances is involved in the bitter taste transduction mechanism.

Animals↗
PubMed1999

Effects of ionic compositions of the medium on monosodium glutamate binding to taste epithelial cells.

Monosodium glutamate and nucleotides are umami taste substances in animals and have a synergistic effect on each other. We studied the ligand-binding properties of the glutamate receptors in taste epithelial cells isolated from bovine tongue. Specific glutamate binding was observed in an enriched suspension of taste receptor cells in Hanks' balanced salt solution, while no specific glutamate binding was apparent in the absence of divalent ions or when the cells had been depolarized by a high content of potassium in Hanks' balanced salt solution. There was no significant difference between the release of glutamate under depolarized or divalent ion-free conditions and under normal conditions. However, glutamate was easily released from the depolarized cells in the absence of divalent ions. These data suggest that the binding of glutamate to receptors depends on divalent ions, which also have an effect on maintaining binding between glutamate and receptors.

Animals↗
PubMed1998

Noise analysis of the quinine-induced current in frog taste receptor cells.

It has been shown that quinine, a bitter tasting substance, induces a cationic membrane current in frog taste receptor cells. We analyzed the quinine-induced current fluctuation to further characterize the cationic channel conducting the current. Taste cells were enzymatically isolated from fungiform papillae of the bullfrog tongue. Membrane currents were recorded under voltage-clamp by using the whole-cell patch clamp technique. A Cs(+)-containing pipette solution was used to block K+ currents. When quinine was bath applied, it induced a steady inward current in cells held at -60 mV. The current data were digitized at a sampling frequency of 2 kHz after having been low-pass filtered (cut-off frequency, 1 kHz). The spectral density distribution was calculated by 1024 points fast Fourier transform (FFT), and was fitted by a sum of two Lorentzian functions, with corner frequencies at 10-20 Hz and at 90-120 Hz. The single-channel conductance calculated from the variance versus mean current plot was 5 pS in a normal saline solution containing 1.8 mM Ca2+. In a nominally Ca(2+)-free solution, the single-channel current was doubled. Our previous study has shown that the quinine-induced current is enhanced in low extracellular [Ca2+]. This enhancement could be partly attributable to the Ca2+ suppression of the single-channel conductance.

Analgesics, Non-Narcotic↗
PubMed1997

New xenograft model of multiple myeloma and efficacy of a humanized antibody against human interleukin-6 receptor.

A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 x 10(6) KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti-IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6-dependent KPMM2 cells.

Animals↗
PubMed1996

A quinine-activated cationic conductance in vertebrate taste receptor cells.

The chincona alkaloid quinine is known to be a bitter tasting substance for various vertebrates. We examined the effects of quinine on isolated taste receptor cells from the bullfrog (Rana catesbeiana). Membrane currents were recorded by whole-cell recording, while quinine hydrochloride was applied extracellularly from a puffer pipette. At the resting potential (-77 +/- 9 mV, mean +/- SD, n = 49 cells), taste cells generated inward currents in response to quinine stimulation (> 1 mM), indicating a depolarizing response in the taste cells. Two types of current responses were observed; a newly found quinine-activated cationic conductance and a previously reported blocking effect of quinine on K+ conductances. The cationic current was isolated from the K+ current by using a Cs(+)-containing patch pipette. The relative permeabilities (Pion) of the quinine-activated cationic conductance were: PNa/PK/PCs = 1:0.5:0.42. The quinine dose-response relation was described by the Hill equation with the K1/2 of 3.6 mM and Hill coefficient of 5.3. When extracellular [Ca2+] (1.8 mM) was reduced to nominally free, the conductance was enhanced by about sixfold. This property is consistent with observations on quinine responses recorded from the gustatory nerve, in vivo. The quinine-induced cationic current was decreased with an application of 8-bromo-cAMP. We conclude that the bitter substance quinine activates a cation channel in taste receptor cells and this channel plays an important role in bitter taste transduction.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Menopause-related changes in bone mineral density in Japanese women: a longitudinal study on lumbar spine and proximal femur.

We investigated 2-year longitudinal changes of bone mineral density (BMD) in lumbar spine and proximal femur in 64 Japanese women aged 38-67. Forty subjects were premenopausal (mean age 44.9) and 24 postmenopausal (mean age 54.6) at enrollment of the study. Six subjects experienced menopause during the 2-year study period and were defined as the perimenopausal group. Measurements of BMD were performed using dual-energy X-ray absorptiometry at L2-4, femoral neck, greater trochanter, and Ward's triangle. Paired t test revealed no significant decrease in BMD at any site in the premenopausal group. Significant annual decrease in BMD was observed in the perimenopausal group at L2-4, femoral neck, and greater trochanter. A similar tendency was observed in Ward's triangle, but did not reach statistical significance. In the postmenopausal group, significant decrease in BMD was found at the proximal femur, but not at L2-4. Significant inverse correlation between age and change rate of BMD was found at L2-4, but not at the proximal femur, in premenopausal women. In postmenopausal women, there was a significant association between body weight (BW) change and change rate in BMD at L2-4, femoral neck, or greater trochanter. This association was not found in the premenopausal group. These results suggest that effect of menopause on BMD may be different in individuals and sites of the skeleton. BW change may affect change in BMD in postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Relationship between respiratory muscle strength and lean body mass in men with COPD.

It has been suggested that low body weight may be associated with decreased respiratory muscle function in COPD, but the precise mechanism is not known. Since body compositional change inevitably accompanies body weight change, we decided to study the possible relationship between respiratory muscle strength and body composition in patients with COPD. We studied respiratory muscle strength, pulmonary function, and body composition in 24 Japanese male patients with COPD. Patients were divided into two groups according to their body weight (group A, body weight lower than 80% of ideal body weight vs group B, 80% or more) and a comparison was made together with age-matched controls (group C). Maximal inspiratory mouth pressure (PImax) and maximal expiratory mouth pressure (PEmax) were measured by a previously reported method. Body compositional analysis was performed using dual energy x-ray absorptiometry (DXA; Norland XR26). It showed significantly lower fat body mass (FAT), FAT/body weight%, and lean body mass (LEAN) in group A than those in group B. The PImax in group A was significantly lower than that in group B and C (44.2 +/- 13.8, 76.4 +/- 29.9, and 88.6 +/- 18.1 cm H2O, respectively). PEmax in group A was also significantly lower than that in group B and group C (61.9 +/- 20.1, 86.7 +/- 26.8, and 90.4 +/- 17.6 cm H2O, respectively). Both PImax and PEmax were significantly correlated with LEAN (r = 0.656, r = 0.591, p < 0.01, respectively) in patients with COPD. These results show that respiratory muscle strength is closely associated with body weight and lean body mass in patients with COPD. The present approach to compare respiratory muscle strength with lean body mass should be useful for studying the mechanism of respiratory muscle weakness in patients with COPD.

Absorptiometry, Photon↗
PubMed1994

Radial bone mineral content of normal Japanese infants and prepubertal children: influence of age, sex and body size.

The present study was performed to measure appendicular bone mass of Japanese infants and children, and to assess the influence of age, sex and body size on bone mass during the period of bone growth. The bone mineral content (BMC) and bone width (BW) at the distal third of the radius were measured by single photon absorptiometry (SPA) in 229 healthy Japanese infants and children aged 0-12 years, and the BMC/BW ratio was calculated to give the bone mineral density (BMD). BMC and BW increased with age until 2 years, while BMD did not obviously change until 2 years. After 2 years of age, the overall effect of aging appeared more prominent in BMC and BMD than in BW. There were no significant differences in BMC, BW and BMD between males and females aged 0-12 years. Age, body height, and body weight were strongly correlated with three parameters of bone mass (BMC, BW, and BMD). Among the three parameters of bone mass, BMC showed the highest Pearson coefficient of correlation with age (r = 0.955), body height (r = 0.957) and body weight (r = 0.966), as compared with BW and BMD. The present cross-sectional study provides normative data of the appendicular bone mass in healthy Japanese children, which may serve as a standard for assessment of bone mineralization in Japanese infants and children with medical problems.

Absorptiometry, Photon↗
PubMed1993

Age- and gender-related changes in body composition in Japanese subjects.

Age-dependent changes in body composition, namely a decrease in bone mass and lean mass and a reciprocal increase in fat mass, are often observed in normal populations. The recent development of dual-energy x-ray absorptiometry (DXA) made it possible to analyze bone mineral content (BMC), fat mass (fat), and lean body mass (LBM) more precisely and easily. We measured BMC, fat, and LBM in Japanese subjects by DXA to describe the changes in body composition with aging in the Japanese population. A total of 34 female (aged 20-74) and 34 male (aged 18-78) volunteers were divided into three groups according to their age: young (18-22 years), middle-aged (39-48 years), and old (61-78 years). Mean values for body height (BH), body weight (BW), and body mass index (BMI) of the subjects were very similar to Japanese normative values. The BMI of the middle-aged group was the highest of all groups of both sexes. BMC decreased significantly with aging in females but not in males. A decrease in LBM and a reciprocal increase in fat were found between young and middle-aged males but not in females. The correlation between BMC and LBM tends to be greater in males than in females. On the other hand, the correlation between BMC and fat was greater in females than males. These results demonstrate the age- and gender-related difference in body components in Japanese subjects. DXA may be useful for the analysis of body composition in different age and sex groups.

Absorptiometry, Photon↗
PubMed1992

[Combination therapy of a new platinum complex, DWA2114R with various antitumor agents against mouse tumors in vivo].

In vivo antitumor activity of (-)-(R)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) monohydrate (DWA2114R) in combination with various antitumor agents was examined using mouse leukemia P388, Meth-A fibrosarcoma and M5076 reticulum cell sarcoma. The combination treatment of DWA2114R with cyclophosphamide, 5-fluorouracil, adriamycin, etoposide or vindesine showed synergistic effects on the prolongation of survival time of mice bearing P388. Among these combinations, combination of DWA2114R with adriamycin or vindesine showed a good synergism. In the combination treatment with vindesine against Meth-A which is not so sensitive to platinum agent, DWA2114R showed a synergistic or additive effect, but cis-diamminedichloroplatinum (II) (CDDP) showed subadditive. Three-drug combination of DWA2114R or CDDP with cyclophosphamide and adriamycin was examined in mice inoculated i.p. or s.c. with M5076. In both models, the combination of DWA2114R was more active than that of CDDP at the dose less than 1/16-fold of the dose of CDDP which is the ratio of two drugs in clinical trial.

Animals↗
PubMed1991

Bone histomorphometric analysis for the cause of osteopenia in vitamin C-deficient rat (ODS rat).

A particular strain of rat, the osteogenic disorder rat (ODS rat), was established in 1973. Phenotypic expression of od/od in ODS rat develops signs characteristics of a vitamin C-deficient animal, with bleeding tendencies and limb fractures. We investigated the bone histomorphometry to clarify the pathogenesis of osteopathy found in ODS rat. Bone histomorphometry revealed that static parameters reflecting bone formation were found to be remarkably decreased in od/od rats. These observations were more prominent in the metaphysis of distal femurs of od/od rats than those in the tail vertebrae. Parameters reflecting bone resorption in od/od rats were reduced in the distal femoral metaphysis, but were similar to those of controls in the tail vertebrae. These parameters were restored to control levels after ascorbic acid supplementation to pair-fed od/od rats. The mineral appositional rate in od/od rats was not significantly different from that in controls. Although body weight gain in pair-fed controls was significantly reduced compared to those fed ad libitum, histomorphometric parameters, on the contrary, were unaltered between these groups. Our present study provides evidence that the cause of osteopenia found in od/od rat is attributable to an imbalance between the total amounts of resorption and formation, and the pathogenesis of osteopathy could be due to ascorbic acid deficiency itself rather than malnutrition.

Alkaline Phosphatase↗
PubMed1991

Therapeutic trial of hematological disorders with intermittent administration of high-dose 1-alpha-hydroxyvitamin D3.

Aplastic anemia and myelodysplastic syndrome were successfully treated with an intermittent administration of high-dose 1 alpha-hydroxy-vitamin D3, an active analogue of 1,25-dihydroxyvitamin D3. This effect was considered to be through the differentiation-inducing and immunomodulatory actions of 1,25-dihydroxyvitamin D3. The only adverse effect was hypercalciuria which was controllable by decreasing the dose.

Adult↗
PubMed1990

Quantitative bone histomorphometry and circulating T lymphocyte subsets in postmenopausal osteoporosis.

To explore the influence of the immune system on the development of osteoporosis, 19 untreated postmenopausal women with osteoporosis were studied by means of quantitative histomorphometry of the ilium and an analysis of T lymphocyte subsets in the peripheral blood. Osteoporotic women had lower OKT3+ and OKT8+ counts and a higher OKT4+/OKT8+ ratio than nonosteoporotic control subjects. Linear regression analyses disclosed that the age of subjects correlated with bone mineral density (BMD; r = -0.634, p less than 0.01) and some of the histomorphometric parameters for bone formation (r = -0.694 to -0.467, p less than 0.01-0.05). The number of OKT4+ cells showed weak but significant negative correlation with the parameters for bone resorption (r = -0.549 to -0.462, p less than 0.05). In a multiple regression analysis, the advanced age, the increase in OKT3+, and the decrease in OKT4+ and OKT8+ counts were shown to be significant predictors for the decrease in BMD (R = 0.882, p less than 0.01). According to the regression formula obtained from the analysis, the parameters for bone formation were related only to the age of subjects whereas those for bone resorption were tightly associated with the number of OKT4+ and OKT8+ cells but not with the age of subjects. These results indicated that, in addition to the age factor, abnormalities of the peripheral T lymphocyte subsets, especially those of OKT4+ and OKT8+ cells, are closely associated with the decrease in bone mass in postmenopausal osteoporosis, supporting the causal relationship between T lymphocyte functions and the development of postmenopausal osteoporosis.

Aged↗
PubMed1989

Quantitative computed tomography of lumbar vertebrae in Japanese patients with osteoporosis.

Vertebral trabecular bone mineral density of both healthy Japanese subjects and Japanese patients with osteoporosis was measured by quantitative computed tomography (QCT) technique. The age-related reduction rate in vertebral trabecular bone mineral density of control females averaged 1.1% per year, from age 20 to 80, with an accelerated loss demonstrated after age 40. In the male controls, trabecular bone mineral density declined by an average of 0.9% per year. These values were found to be similar to the University of California at San Francisco (UCSF) QCT data (US Caucasians: 1.2% for female, 0.72% for male). Therefore, it appears that age-related rates of trabecular bone loss in the lumbar vertebrae may be similar for both Japanese and Caucasians. However, when compared to average values in UCSF QCT data of comparable age and sex, the mean values in Japanese appear to be approximately 10-20 mg/cm3 lower than Caucasian counterparts. All female patients with osteoporosis as evidenced by atraumatic vertebral fracture had QCT values below 50 mg/cm3. It is suggested that the Japanese may have lower trabecular bone mineral density than Caucasians but may also have a lower threshold for fracture of the vertebrae. Further studies are needed to establish the possible racial differences in vertebral trabecular bone mineral density, and to determine whether these possible disparities are related to genetic differences, or to differences in body size, dietary intake, physical activity or other lifestyle/environmental factors.

Adult↗