Search PubMed⌕ Search

Biomedical subjects

T Yoshioka

Publications and source records attributed to T Yoshioka.

At least 37 records · Page 2Linked to original sources
PubMed2004

Heat stress facilitates the recovery of atrophied soleus muscle in rat.

Effects of heat stress on the recovery of atrophied soleus muscle were studied in rats. Ten-week-old male Wistar rats were randomly divided into cage control (CC) and 5-day hindlimb suspension group (HS). The half of the rats in group HS was exposed to heat stress (41 degrees C for 60 min) in an incubator immediately after the hindlimb suspension (HS-H) and the other group of rats was not heat stressed (HS-C) prior to 10 days of ambulation recovery. One group of cage control rats (CH) was also exposed to heat similarly. The soleus muscles were dissected at four time points, i.e., immediately after the suspension (or heat stress), and 3, 5, and 10 days after the recovery (n=8 per group at each time point). The absolute wet weight and water and protein content of whole soleus muscle in group HS-C were approximately 36, 27, and 8 mg less than CC (p <0.05). Thus, the percentage contribution of water and protein loss to the decrease in muscle weight was 75 and 22%, respectively. Although water content, as well as muscle weight, was elevated within 3 days, the increase of protein was delayed. Heat exposure prior to recovery accelerated the increase in protein content even in the control group. These phenomena were closely associated with 72-kD heat shock protein (HSP72) content. It is suggested that heat stress applied at the end of hindlimb unloading facilitated the recovery of atrophied soleus muscle of rat, through possibly HSP72-related events of protein metabolism. The data also indicated that the combination of heat and mechanical stress evoked larger and long lasting HSP72 response than does heat or mechanical stress alone.

Adaptation, Physiological↗
PubMed2003

Effects of heat stress and mechanical stretch on protein expression in cultured skeletal muscle cells.

Effects of heat stress, mechanical stretching or a combination of both on the expression of heat shock proteins (HSPs) and total protein level were studied in a culture system. Rat skeletal muscle cells (L6) were cultured on flexible-bottomed culture plates. They were subjected to one of the four following conditions: (1) 97 h incubation at 37 degrees C, (2) 1 h incubation at 41 degrees C followed by 96 h incubation at 37 degrees C, (3) 1 h incubation at 37 degrees C followed by 96 h cyclic stretching (18% of initial length, 2-s stretch and 4-s release) at 37 degrees C or (4) 1 h incubation at 41 degrees C followed by 96 h cyclic stretching at 37 degrees C. The expression of HSP72 and HSP90 and total protein was determined in the crude homogenates, supernatant and pellets. Cellular protein concentrations in the homogenates and pellets were increased by heat stress and/or mechanical stress (stretch). A cumulative effect of the combination of heating and stretch on the protein concentration in the homogenates and in the pellets was noted. The expressions of HSP72 and HSP90 in the pellets were also increased by heat stress and/or stretch. However, HSP90 in the supernatant did not change following heat stress and/or stretch. The regulation of HSP72 and HSP90 expression in skeletal muscle cells may be closely related to total protein, the abundance of which is also stimulated by mechanical and heat stresses. These observations suggest strongly that heating and passive stretch of muscle may be useful as a means of increasing muscle mass, not only in athletes but also in patients during rehabilitation.

Animals↗
PubMed2003

A new approach for accessing retroperitoneal space using a 5-mm [corrected] visual access cannula.

Retroperitoneal lymph node evaluation is a very important step in planning cancer therapy. Traditional staging laparotomy is too invasive and causes considerable morbidity. However, laparoscopic access of the retroperitoneal space offers the onco-endoscopist a unique, noninvasive, and less dangerous method for assessing and managing women with gynecologic malignancies. The retroperitoneal approach is noninvasive and less dangerous way of accessing the paraaortic space. A new minimally invasive approach of accessing the retroperitoneal space using a 5-mm visual access cannula is introduced. A complete paraaortic and pelvic lymphadenectomy was possible for 60 patients with varied gynecologic malignancies using our retroperitoneal laparoscopic approach. Less blood loss and rapid recovery was observed, and no bowel complication was encountered. The use of the 5-mm visual access cannula offers a less invasive surgical procedure and provides cosmetic advantages.

Adult↗
PubMed2003

DS-Nh as an experimental model of atopic dermatitis induced by Staphylococcus aureus producing staphylococcal enterotoxin C.

DS-Nh mice raised under conventional conditions spontaneously develop dermatitis similar to human atopic dermatitis (AD), which is associated with staphylococcal infection. In the present study, we show that Staphylococcus aureus producing staphylococcus exotoxin C (SEC) was recovered from the culture of the skin lesions of DS-Nh mice with AD-like dermatitis and that the serum levels of anti-SEC antibodies from these mice were elevated. We describe here how to promote experimental AD by epicutaneous injection with SEC-producing S. aureus to DS-Nh mice. In order to assess the role of SEC in the pathogenesis of AD, the mitogenic activity, TCRBV repertoire analysis and the production of IL-4 and IFN-gamma from spleen mononuclear cells (MNC) from DS-Nh stimulated by SEC were compared with those due to SEA, SEB and TSST. The weakest was the mitogenic activity of SEC, and higher IL-4 responses and lower IFN-gamma responses to SEC showed correlation with TCRBV8S2-positive T cells, which were selectively stimulated by SEC. We also demonstrate that SEC-producing S. aureus was able to survive in DS-Nh after intradermal injection. These results suggest a possible role for SEC in the pathogenesis of AD through host-S. aureus relationships.

Animals↗
PubMed2003

[Minimally invasive video-assisted thoracic surgery using radially expanding trocars].

We report a new and safer access device for thoracoscopic operation. This radially expanding trocar provides a smaller incision of skin and a lesser visceral, vascular or neural injury than a conventional cannula. Therefore, most of patients undergoing this operation do not feel much pain. Moreover, this device system is more cost effective than a conventional one. We prefer and recommend this minimally invasive technique for video-assisted thoracic surgery.

Equipment Design↗
PubMed2002

A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.

OBJECTIVE: The effects of pretreatment with ONO-4007, a lipid A analog, on cutaneous plasma leakage induced by ONO-4007, lipopolysaccharide (LPS) and inflammatory mediators were investigated. MATERIAL: Male ddY strain mice. TREATMENT: Mice were pretreated with ONO-4007 (up to 6 mg/kg i.p.), 0-24 h prior to plasma leakage study. METHODS: Plasma extravasation was determined by dye leakage. RESULTS: Systemic ONO-4007 (6 mg/kg i. p.) pretreatment for 2 to 12 h inhibited plasma extravasation in the mouse skin elicited by ONO-4007 and LPS. The inhibition was dose-dependent. Plasma leakage induced by platelet-activating factor (PAF), histamine and 5-hydroxytryptamine (5-HT) was also inhibited by ONO-4007 pretreatment. Plasma corticosterone levels increased 2 and 4 h after systemic ONO-4007 (6 mg/kg) administration and returned to the control level 24 h later. Adrenalectomy and metyrapone but not propranolol reversed the inhibition by ONO-4007 pretreatment of LPS-induced plasma leakage. CONCLUSIONS: A single injection of ONO-4007 in mice induced transient tolerance to plasma leakage elicited by LPS, ONO-4007 and inflammatory mediators. Endogenous corticosterone, at least in part, plays a role in the development of tolerance.

Adrenal Glands↗
PubMed2002

Distinct TCRAV and TCRBV repertoire and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation.

Acute graft-versus-host disease (GVHD) is a disorder involving the skin, gut and liver that is caused by mismatches of major and/or minor histocompatibility antigens between the HLA-identical donor and recipient. If T lymphocytes infiltrating GVHD lesions recognize antigens expressed in these organs, T cell clones should expand in inflammatory tissues. We previously reported that recipients of allogeneic bone marrow grafts have clonally expanded TCRalphabeta(+) T lymphocytes soon after transplantation, which leads to a skew of TCR repertoires. To establish whether or not the same antigens cause clonal expansion of T lymphocytes in both blood and GVHD tissues, we examined the usage of TCR alpha and beta chain variable regions (TCRAV and TCRBV) and determined the complementarity-determining region 3 (CDR3) of T lymphocytes clonally expanded in circulating blood and GVHD lesions. We found that the repertoires and CDR3 diversity of TCRAV and TCRBV differed between the GVHD lesions and circulating blood, suggesting the selective recruitment of antigen-specific T cells into GVHD tissues. We also found that the usage of TCRAV and TCRBV by the clonally expanded T lymphocytes and their CDR3 sequences differed between the GVHD tissues and blood. These results suggest that the antigen specificity of TCRalphabeta(+) T lymphocytes clonally expanded in blood and GVHD lesions is different.

Acute Disease↗
PubMed2002

A scanning electron microscopic study of dentinal erosion by final irrigation with EDTA and NaOCl solutions.

AIM: The purpose of this in vitro study was to examine dentinal erosion caused by final irrigation with EDTA and NaOCl. METHODOLOGY: Twenty-five single-rooted human teeth were instrumented with rotary nickel-titanium Series 29 Profile Instruments. The teeth were divided into five groups and subjected to final irrigation as follows: group A, irrigated with 6% NaOCl (3 mL) for 2 min; group B, 15% EDTA (3 mL) for 1 min; group C, 15% EDTA (3 mL) for 1 min, followed by 6% NaOCl (3 mL) for 2 min; group D, 15% EDTA (3 mL) for 3 min and group E, 15% EDTA (3 mL) for 3 min, followed by 6% NaOCl (3 mL) for 2 min. Photomicrographs of dentinal walls were produced using a scanning electron microscope (3000 x) at 1, 3 and 6 mm from the apex. The amount of debris and dentinal tubule diameter were evaluated, and values were statistically analysed using one-way ANOVA and Fisher's PLSD test. RESULTS: When the root canal was irrigated with 15% EDTA alone, the dentine had a smooth and plane appearance, and dentinal tubule orifices were regular and separated. When the root canal was irrigated with EDTA followed by NaOCL the dentine was eroded and the dentinal tubule orifices were irregular and rough. Dentinal tubule diameter increased to 3.43 +/- 0.23 microm in group C and to 3.93 +/- 0.44 microm in group E. Significant differences were observed between groups B and C, and between groups D and E (P < 0.05). However, more debris was removed by irrigation with EDTA followed by NaOCl than with EDTA alone (P < 0.05). CONCLUSIONS: Final irrigation with 6% NaOCl accelerates dentinal erosion following treatment with 15% EDTA.

Analysis of Variance↗
PubMed2001

Sequence-dependent antitumor efficacy of combination chemotherapy with nedaplatin, a newly developed platinum, and paclitaxel.

We evaluated the sequence dependency of antitumor efficacy and toxicity in combination therapy of nedaplatin (NDP) with paclitaxel (TXL) against Lewis lung carcinoma. The sequential administration of NDP prior to TXL (NT therapy) resulted in severe body weight loss followed by frequent toxic death of mice. In contrast, the sequential dosing of TXL prior to NDP (TN therapy) resulted in synergistically enhanced inhibition of tumor growth with less toxicity compared with the NT therapy. Comparing the antitumor activity of NDP plus TXL with that of cisplatin (CDDP) plus TXL or carboplatin (CBDCA) plus TXL, the combination effect of NDP plus TXL was significantly higher than that of CDDP plus TXL or CBDCA plus TXL. These results indicate that the TN therapy may have significant potential in clinical use.

Animals↗
PubMed2001

Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells.

Understanding the process of inducing T cell activation has been hampered by the complex interactions between APC and inflammatory Th1 cells. To dissociate Ag-specific signaling through the TCR from costimulatory signaling, rTCR ligands (RTL) containing the alpha1 and beta1 domains of HLA-DR2b (DRA*0101:DRB1*1501) covalently linked with either the myelin basic protein peptide 85-99 (RTL303) or CABL-b3a2 (RTL311) peptides were constructed to provide a minimal ligand for peptide-specific TCRs. When incubated with peptide-specific Th1 cell clones in the absence of APC or costimulatory molecules, only the cognate RTL induced partial activation through the TCR. This partial activation included rapid TCR zeta-chain phosphorylation, calcium mobilization, and reduced extracellular signal-related kinase activity, as well as IL-10 production, but not proliferation or other obvious phenotypic changes. On restimulation with APC/peptide, the RTL-pretreated Th1 clones had reduced proliferation and secreted less IFN-gamma; IL-10 production persisted. These findings reveal for the first time the rudimentary signaling pattern delivered by initial engagement of the external TCR interface, which is further supplemented by coactivation molecules. Activation with RTLs provides a novel strategy for generating autoantigen-specific bystander suppression useful for treatment of complex autoimmune diseases.

Calcium Signaling↗
PubMed2001

Impaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice.

To elucidate the functional role of phospholipase Cbeta4 (PLCbeta4), which is highly expressed in the Purkinje cells of the rostral cerebellum, cerebellar long-term depression (LTD) and delay and trace eyeblink conditioning were investigated in PLCbeta4-deficient mice. Rostral cerebellar LTD and delay eyeblink conditioning were severely impaired, whereas trace eyeblink conditioning was not. These results indicate that PLCbeta4 is essential for LTD in the rostral cerebellum and delay conditioning, but not trace conditioning. Rostral cerebellar LTD may be required as a neural substrate for delay conditioning, but is not required for trace conditioning.

Afferent Pathways↗
PubMed2001

Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.

Animals↗
PubMed2001

Neural coding mechanisms underlying perceived roughness of finely textured surfaces.

Combined psychophysical and neurophysiological studies have shown that the perceived roughness of surfaces with element spacings of >1 mm is based on spatial variation in the firing rates of slowly adapting type 1 (SA1) afferents (mean absolute difference in firing rates between SA1 afferents with receptive fields separated by approximately 2 mm). The question addressed here is whether this mechanism accounts for the perceived roughness of surfaces with element spacings of <1 mm. Twenty triangular and trapezoidal gratings plus a smooth surface were used as stimulus patterns [spatial periods, 0.1-2.0 mm; groove widths (GWs), 0.1-2.0 mm; and ridge widths (RWs), 0-1.0 mm]. In the human psychophysical studies, we found that the following equation described the mean roughness magnitude estimates of the subjects accurately (0.99 correlation): 0.2 + 1.6GW - 0.5RW - 0.25GW(2). In the neurophysiological studies, these surfaces were scanned across the receptive fields of SA1, rapidly adapting, and Pacinian (PC) afferents, innervating the glabrous skin of anesthetized macaque monkeys. SA1 spatial variation was highly correlated (0.97) with human roughness judgments. There was no consistent relationship between PC responses and roughness judgments; PC afferents responded strongly and almost equally to all of the patterns. Spatial variation in SA1 firing rates is the only neural code that accounts for the perceived roughness of surfaces with finely and coarsely spaced elements. When surface elements are widely spaced, the spatial variation in firing rates is determined primarily by the surface pattern; when the elements are finely spaced, the variation in firing rates between SA1 afferents is determined by stochastic variation in spike rates.

Action Potentials↗
PubMed2001

Structure-activity relationships in the deacetylation of O-glucosides of N-hydroxy-N-arylacylamides by mammalian liver microsomes.

Structure-activity relationships in the deacylation of O-glucosides of N-hydroxy-N-aryl-acylamides were investigated to provide insights into the metabolic activation of carcinogenic/mutagenic O-glycosides of N-hydroxy-N-arylacylamides. In the subcellular fractions obtained from porcine liver, the deacetylation activity toward O-glucoside of N-hydroxyacetanilide (GAc) was mainly localized in the microsomes. Both the 2-chloro (2ClGAc) and 2-methyl (2MeGAc) derivatives of GAc were not deacetylated by the microsomes. Other compounds having either 3- or 4-substituent (chloro or methyl), however, were deacetylated and showed higher V(max)/K(m) values than that of GAc. 4-Methyl derivative (4MeGAc) was shown to competitively inhibit the deacetylation activity toward GAc, and the K(i) value of 4MeGAc was comparable with its K(m) value obtained in the microsome-catalyzed deacetylation. These apparent K(m) values were shown to correspond to their lipophilicities estimated from retention times on high-performance liquid chromatography (HPLC). As for the effect of acyl groups, the order of V(max)/K(m) values was N-propionyl derivative (GPr)>GAc>N-butyryl derivative (GBu). From the optimized structures and energy levels of the frontier orbitals of these compounds, calculated by the semi-empirical AM1 method, the effects of 2-substituents and acyl groups on the deacetylation activity is thought to be due to a steric factor. From the energy levels of the frontier orbitals of GAc and its 3- or 4-substituted derivatives, the compound having a lower level of LUMO was shown to be deacetylated effectively. There were marked species differences in the microsomal deacetylation activity toward GAc, and the highest activity was found in the rabbit, followed by the porcine, hamster, rat and then bovine liver microsomes.

Aniline Compounds↗
PubMed2001

Ion selectivities of the Ca(2+) sensors for exocytosis in rat phaeochromocytoma cells.

1. The ion selectivities of the Ca(2+) sensors for the two components of exocytosis in rat phaeochromocytoma (PC12) cells were examined by measurement of membrane capacitance and amperometry. The cytosolic concentrations of metal ions were increased by photolysis of caged-Ca(2+) compounds and measured with low-affinity indicators benzothiazole coumarin (BTC) or 5-nitrobenzothiazole coumarin (BTC-5N). 2. The Ca(2+)-induced increases in membrane capacitance comprised two phases with time constants of 30--100 ms and 5 s. Amperometric events reflecting the exocytosis of large dense-core vesicles occurred selectively in the slow phase, even with increases in the cytosolic Ca(2+) concentration of > 0.1 mM. 3. The slow component of exocytosis was activated by all metal ions investigated, including Cd(2+) (median effective concentration, 18 pM), Mn(2+) (500 nM), Co(2+) (900 nM), Ca(2+) (8 microM), Sr(2+) (180 microM), Ba(2+) (280 microM) and Mg(2+) (> 5 mM). In contrast, the fast component of exocytosis was activated by Cd(2+) (26 pM), Mn(2+) (620 nM), Ca(2+) (24 microM) and Sr(2+) (320 microM), but was only slightly increased by Ba(2+) (> 2 mM) and Co(2+) and not at all by Mg(2+). 4. The fast component, but not the slow component, was competitively blocked by Na(+) (median effective concentration, 44 mM) but not by Li(+), K(+) or Cs(+). Thus, the Ca(2+) sensor for the fast component of exocytosis is more selective than is that for the slow component; moreover, this selectivity appears to be based on ionic radius, with cations with radii of 0.84 to 1.13 A (1 A = 0.1 nm) being effective. 5. These data support a role for synaptotagmin--phospholipid as the Ca(2+) sensor for the exocytosis of large dense-core vesicles and they suggest that an additional Ca(2+)-sensing mechanism operates in the synchronous exocytosis of synaptic-like vesicles.

Animals↗
PubMed2001

Antitumor effect of a new selective matrix metalloproteinase inhibitor, MMI-166, on experimental pancreatic cancer.

The antitumor effect of a new matrix metalloproteinase inhibitor, MMI-166, which is a selective inhibitor of MMP-2 and -9, was examined in the hamster pancreatic cancer cell line PGHAM-1. In vitro, MMI-166 inhibited the gelatinase activity of MMP-2 and -9 derived from PGHAM-1 cells, and dose-dependently inhibited invasion of PGHAM-1 through a basement membrane-like barrier. MMI-166 showed no apparent cytotoxicity to PGHAM-1 cells in culture at 100 microgram/ml. MMI-166 (200 mg/kg) or vehicle were administered orally, once daily, from day 1 until day 21 after implantation in the orthotopic implantation model of PGHAM-1. MMI-166 significantly reduced the incidence of liver surface metastasis from 66.7% to 20.0%, and it reduced the number of liver surface metastases per animal from 6.17 to 2.00, but this reduction was not significant. MMI-166 significantly reduced the volume of pancreatic tumors from 718.3 +/- 220.0 mm(3) to 222.8 +/- 85.4 mm(3). Treatment of pancreatic tumors with MMI-166 caused a significant reduction in the microvessel density from 37.90 +/- 10.18/mm(2) to 16.16 +/- 3.15/mm(2) and a significant increase in apoptotic index from 1.75 +/- 0.41% to 3.96 +/- 0.38%, but there was no significant difference between tumor cell proliferation in the MMI-166-group and the control group. These results showed that selective MMP inhibition could limit both cancer spread and angiogenesis in pancreatic cancer. The selective MMP-2 and -9 inhibitor MMI-166 may be of therapeutic use in the treatment of pancreatic cancer because of its inhibitory effect on invasion and angiogenesis.

Animals↗
PubMed2001

Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA.

Human type II iodothyronine deiodinase (hDII) belongs to a family of selenoproteins. It catalyzes 5'-deiodination of thyroxine to generate an active thyroid hormone, 3,3',5-triiodothyronine. Two novel splice variants of hDII gene transcript; namely hDII-b and hDII-c, were identified. Three distinct DNA fragments (hDII-a-c) were amplified by a reverse transcription-polymerase chain reaction (RT-PCR) with hDII intron-spanning primers using total-RNA from human umbilical vein endothelial cell line, ECV304. The sequence of hDII-a was identical to that of previously reported hDII. hDII-b and hDII-c had an additional insertion of 108 and 242 bp, respectively. The insertion sequences were found in the intron of hDII gene, therefore, two novel exons exist between exons 1 and 2 of hDII gene. The splice sites of new exons (b and c) conserved the consensus sequences of splice acceptor and donor sites. hDII-b contains exon b with an in-frame TGA codon that may encode an extra selenocysteine. hDII-c contained exons b and c and the predicted open reading frame is interrupted by a stop codon (TAA) produced by a frame shift. RT-PCR analysis showed that hDII-a and hDII-b mRNAs are expressed in human tissues including brain, kidney, lung and trachea. The mRNA abundance of hDII-c was lower than that of hDII-a or hDII-b. Thus, the new variants of hDII transcripts suggest the presence of two short exons between exons 1 and 2 of hDII gene, and of functional variant of hDII.

Alternative Splicing↗