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T Goto

Publications and source records attributed to T Goto.

At least 19 recordsLinked to original sources

Substance P stimulates late-stage rat osteoblastic bone formation through neurokinin-1 receptors.

Substance P (SP) is a widely distributed neuropeptide that works as a neurotransmitter and neuromodulator. Recently, SP receptors, particularly neurokinin-1 receptors (NK(1)-Rs) that have a high affinity for SP, have been observed not only in neuron and immune cells, but also in other peripheral cells, including bone cells. To identify the role of SP in bone formation, we investigated the expression of NK(1)-Rs in osteoblastic cells and the effects of SP on bone formation by rat calvarial osteoblastic cells. Rat calvarial osteoblastic cells were isolated and cultured for 3 weeks in alpha-MEM containing 10% serum, ascorbic acid, dexamethasone, and beta-glycerophosphate. We then investigated NK(1)-R expression, SP effects on osteoblastic bone formation, and osteocalcin mRNA expression in osteoblastic cells. RT-PCR and immunocytochemistry showed that NK(1)-R mRNA was expressed and NK(1)-R was present in 14-day, but not 7-day, cultured calvarial osteoblasts. Bone formation by cultured osteoblastic cells significantly increased after the addition of 10(-8)-10(-6)MSP. During 3 weeks of culture, the addition of SP in the first week did not significantly increase bone formation, whereas adding SP during the first and second week or all 3 weeks significantly increased calvarial osteoblastic bone formation. Furthermore, semi-quantitative RT-PCR indicated that SP stimulated osteocalcin mRNA expression in the osteoblasts at day 14 or day 21, whereas SP did not stimulated the runX2 or type I collagen mRNA expression at day 7 but stimulated them at day 14. These results indicate that SP stimulates bone formation by osteoblastic cells via NK(1)-Rs at late-stage bone formation. These effects were dependent on the expression of NK(1)-R in osteoblastic cells. Our findings suggest that SP secreted from sensory neurons may modulate bone formation after the expression of SP receptors.

Animals↗

Optimal low-energy laser irradiation causes temporal G2/M arrest on rat calvarial osteoblasts.

Low-energy laser irradiation (LELI) accelerates wound healing and is thought to accelerate bone formation. However, the mechanism of laser healing is not clear. To clarify the biological mechanism of LELI healing, we investigated the effects of LELI on rat osteoblasts in vitro. Osteoblastic cells from 3-day-old Wistar rat calvaria were irradiated using a low-energy gallium-aluminum-arsenide (Ga-Al-As) diode laser. Bone formation, osteoblast differentiation, and cell proliferation were evaluated by von Kossa staining, reverse-transcription polymerase chain reaction, alkaline phosphatase (ALP) staining, 5-bromo-2'-deoxyuridine (BrdU) uptake, and fluorescence-activated cell sorter (FACS) analysis. At 21 days after LELI, the greatest bone formation was observed with irradiation energy of 3.75 J/cm2 and the first week after seeding. LELI (3.75 J/cm2) induced an increased number of cells at day 3. LELI-stimulated differentiation in osteoblastic cells was demonstrated by the increases of Runx2 expression and ALP-positive colonies. By contrast, at 1 day after laser irradiation, the number of cells in the irradiation group was significantly lower than that in the control group. BrdU uptake indicated lower proliferation 12 and 24 hours after irradiation compared with the control. Furthermore, FACS data demonstrated a higher proportion of cells in the G2/M phase of the cell cycle 12 hours after irradiation compared with the control. G2/M arrest was confirmed by the appearance of G2/M arrest marker 14-3-3-sigma or phospho-p53. These results demonstrate that LELI induces not only acceleration of bone formation but also initial G2/M arrest, which may cause wound healing like tissue repair.

Alkaline Phosphatase↗

Induction of osteoclast-like cells derived from the synovial lavage fluids of patients with temporomandibular joint disorders.

OBJECTIVE: Although biochemical studies have examined the synovial fluid (SF) of patients with temporomandibular joint (TMJ) disorders (TMDs), the details of the molecular mechanism of bone destruction and remodeling remain unknown. In this study, we induced and characterized osteoclast-like cells from the SF of patients with TMD and investigated the participation of these cells in the pathogenesis of TMD. METHODS: We collected SF cells from patients with TMD after a pumping procedure, cultured osteoclast-like cells, and examined their characteristics, including osteoclast markers and bone resorption activities. In addition, we obtained fibroblastic cells from the SF of TMD patients by continuous sub-culturing. Using these fibroblastic cells, we examined fibroblast markers using immunocytochemical staining and analyzed the receptor activator of nuclear-factor-kappaB ligand (RANKL) mRNA levels. Detection of soluble form of RANKL (sRANKL) in the SF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Osteoclast-like cells were induced from the SF cells of patients with TMD by adding recombinant human (rh) macrophage colony stimulating factor (M-CSF) and either 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] or prostaglandin E2 (PGE2). These multinucleated giant cells were positive for tartrate-resistant acid phosphatase (TRAP) and had the ability to absorb bone. The fibroblastic cells from the SF of TMD patients were positive for fibroblast markers and RANKL mRNA was up-regulated. Detection of sRANKL in SF of patient group was significantly higher than control group. CONCLUSION: The results suggest that the joint-infiltrating SF cells from TMD patients play important roles in the pathogenesis of these disorders, which is characterized by progressive bone destruction or remodeling.

Acid Phosphatase↗

Artificial shrinkage of blastocoeles using either a micro-needle or a laser pulse prior to the cooling steps of vitrification improves survival rate and pregnancy outcome of vitrified human blastocysts.

BACKGROUND: Since we reported the first successful birth from a blastocyst vitrified using a cryoloop technique, our results showed that the survival rate of vitrified blastocysts was negatively correlated with the expansion of the blastocoele. We speculated that a large blastocoele may disturb the efficacy of vitrification. Therefore, we evaluated the effectiveness of artificial shrinkage (AS) of blastocoeles before vitrification, on increasing the survival rate of vitrified blastocysts. METHODS: Supernumerary expanded blastocysts on day 5 were vitrified after AS, which was performed by puncturing the blastocoele with a micro-needle, or by making a hole in the blastocoele with a laser pulse. After warming, viable blastocysts (confirmed by re-expansion of the blastocoele) were transferred to patients with hormone replacement cycle. We compared these data with those of our previous report where AS was not carried out. RESULTS: The survival rate was significantly higher (97.2%, 488/502) in this study than that of the previous report (86%). After 266 transferable cycles, 160 patients became pregnant (60.2%), which was significantly higher than our previous results (34.1%, 29/85). The implantation rate was 46.7% (209/448). CONCLUSIONS: Our results revealed that the survival rate and the pregnancy rate of vitrified expanded and hatching blastocysts can be improved by using AS to collapse the blastocele before vitrification.

Adult↗

Iatrogenic amyloid neuropathy in a Japanese patient after sequential liver transplantation.

A 57-year-old woman in Japan, the first recipient of part of a liver from a 58-year-old man with familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin Val30Met who had had sensorimotor polyneuropathy in the lower limbs for 3 years, started to develop sensory neuropathy 7 years after transplantation. Before the July 1998 sequential transplantation, she had been in a hepatic coma at the terminal stage of primary biliary cirrhosis and waiting for deceased donor liver transplantation. In September 2004, biopsy samples of her duodenum first showed amyloid deposition. Although biopsy materials in 2005 and 2006 showed no changes in amyloid deposition, decreased temperature sensation and pain in fingertips and toes were detected at a neurologic examination in March 2006. Thus, clinical symptoms of FAP appeared about 2 years after amyloid deposition started. Nerve conduction velocity studies revealed mild to moderate axonal sensory polyneuropathy without demyelination. Our findings confirmed iatrogenic sensory neuropathy induced by amyloid deposition 7 years after sequential liver transplantation.

Amyloid Neuropathies, Familial↗

Endothelial expression of Fc gamma receptor IIb in the full-term human placenta.

In the third trimester, human placental endothelial cells express Fc gamma receptor IIb (FcgammaRIIb). This expression is unique because FcgammaRIIb is generally expressed on immune cells and is typically undetectable in adult endothelial cells. Recently, we found a novel FcgammaRIIb-defined, IgG-containing organelle in placental endothelial cells; this organelle may be a key structure for the transcytosis of IgG across the endothelial layer. In this study, we verify the expression of FcgammaRIIb in endothelial placenta cells and use reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing analyses to define the expressed FCGR2B mRNA transcript variant. We also investigated the distribution of FCGR2B mRNA and protein within the vascular tree of the full-term human placenta by RT-PCR and quantitative microscopy. The mRNA sequence of FCGR2B expressed specifically in placental endothelial cells is that of transcript variant 2. FcgammaRIIb expression and synthesis occur throughout the placental vascular tree but do not extend into the umbilical cord. This study provides additional information on FcgammaRIIb expression in the human placenta.

Endothelial Cells↗

The alpha2 type IX collagen tryptophan polymorphism is associated with the severity of disc degeneration in younger patients with herniated nucleus pulposus of the lumbar spine.

Tryptophan alleles in COL9A2 (Trp2) and COL9A3 (Trp3) have been linked to lumbar disc diseases in the Finnish population. Although such diseases consist of various pathogenetically different conditions, detailed analysis of each has not been well documented. The aim of this study was to clarify whether the collagen IX tryptophan alleles influence the symptomatic degeneration of the lumbar disc in Japanese patients with herniated nucleus pulposus. We performed a prospective study of 84 patients who underwent lumbar discectomy. The degree of disc degeneration was evaluated by magnetic resonance images in relation to the collagen IX genotype. Twenty patients (21.4%) had the Trp2 allele and no patients had the Trp3 allele. Patients under 40 years with the Trp2 allele showed more severe disc degeneration at the surgical level than did those without the Trp2 allele (odds ratio 6.00, P=0.043). In contrast, patients aged 40 years or over did not show significant association between disc degeneration and collagen IX genotype. Our results suggest that the Trp2 allele is an age-dependent risk factor for the severity of disc degeneration in younger patients with symptomatic herniated nucleus pulposus of the lumbar spine.

Adult↗

Induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro by hepatotoxin rubratoxin B.

To elucidate the mechanism of rubratoxin B toxicity, we investigated rubratoxin B-induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in mice and cultured cells; we also documented the involvement of stress-activated MAP kinases (c-Jun-N-terminal kinases [JNKs] and p38s) in this process. Rubratoxin B significantly (P<0.05) induced serum TIMP-1 levels in mice. Because TIMP-1 is thought to play a crucial role in the process of liver fibrosis, rubratoxin B may cause liver fibrosis. Rubratoxin B enhanced TIMP-1 secretion in HepG2 cells to a peak level of approximately 40 microg/ml. The amount of TIMP-1 mRNA increased with the duration of rubratoxin B treatment; and this hepatotoxin appears to induce TIMP-1 secretion through a transcriptional control mechanism. Unlike similar treatment with rubratoxin B and JNK inhibitor, concomitant treatment with rubratoxin B and p38 inhibitor increased rubratoxin B-induced TIMP-1 secretion, suggesting that p38s (but not JNKs) antagonize this process. In addition, treatment with p38 inhibitor slightly increased the amount of rubratoxin B-induced TIMP-1 mRNA, suggesting that p38s control rubratoxin B-induced TIMP-1 secretion chiefly post-transcriptionally. In this study, we showed that rubratoxin B induces TIMP-1 production in vivo and in vitro and that p38s antagonize rubratoxin B-induced TIMP-1 secretion.

Actins↗

Collinear to spiral spin transformation without changing the modulation wavelength upon ferroelectric transition in Tb1-xDyxMnO3.

Lattice modulation and magnetic structures in magnetoelectric compounds Tb1-xDyxMnO3 have been studied around the ferroelectric (FE) Curie temperature TC by x-ray and neutron diffraction. Temperature-independent modulation vectors through TC are observed for the compounds with 0.50 <or=x<or=0.68. This indicates that ferroelectricity with a polarization (P) along the c axis in the RMnO3 series cannot be ascribed to such an incommensurate-commensurate transition of an antiferromagnetic order as was previously anticipated. A neutron diffraction study with x=0.59 shows that the FE transition is accompanied by the transformation of the Mn-spin alignment from sinusoidal (collinear) antiferromagnetism into a transverse-spiral structure. The observed spiral structure below TC is expected to produce P along the c axis with the "inverse" Dzialoshinski-Moriya interaction, which is consistent with observation.

Journal Article↗

Improvement in motion efficiency of the spirochete Brachyspira pilosicoli in viscous environments.

Spirochetes are unique among swimming bacteria in terms of their lack of external flagella. They actively move in viscous environments, and, surprisingly, the swimming speed of the spirochete Leptospira interrogans has been reported to increase with viscosity in methylcellulose solutions. Many researchers consider that the presence of a loose, quasi-rigid network formed by linear polymer molecules is related to this strange phenomenon. One of the authors has proposed a theory that expresses this idea mathematically and successfully explains the speed properties of an externally flagellated bacterium in viscous environments. This theory predicts that the ratio of swimming speed to wave frequency (v/f ratio, motion efficiency in a sense) increases with viscosity. In this study, we demonstrated a new method of measuring the swimming speed and wave frequency of spirochetes and the motion characteristics of a swine intestinal spirochete, Brachyspira pilosicoli strain NK1f, measured in viscous environments. Several sets of swimming speed and wave frequency data were simultaneously derived from an animation obtained by our method. The v/f ratio of NK1f displayed a tendency to increase with increasing viscosity, suggesting the validity of the above-mentioned theory. Improvement of motion efficiency is at least one of the factors that maintain spirochete motility in viscous environments.

Animals↗

Thermal sensation and thermophysiological responses to metabolic step-changes.

This study investigated the effect on thermal perception and thermophysiological variables of controlled metabolic excursions of various intensities and durations. Twenty-four subjects were alternately seated on a chair or exercised by walking on a treadmill at a temperature predicted to be neutral at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise or decline immediately (within 1 min) after a change of activity, which means that even moderate activity changes of short duration affect thermal perceptions of humans. After approximately 15-20 min under constant activity, subjective thermal responses approximated the steady-state response. The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative average metabolic rate with varying activity levels, e.g. for the prediction of thermal sensation by steady-state comfort models. The activity during the most recent 5 min should be weighted 65%, during the prior 10-5 min 25% and during the prior 20-10 min 10%.

Adult↗

Telecontrolled micromanipulator system (NeuRobot) for minimally invasive neurosurgery.

BACKGROUND: To perform less invasive neurosurgery, a telecontrolled micromanipulator system has been developed and applied to clinical situations. Basic experiments for telesurgery have also been conducted. METHOD: A cadaver head was used to carry out surgical simulation of the opening of the sylvian fissure and third ventriculostomy. After obtaining permission from the Ethical Committee of Shinshu University School of Medicine, part of the recurrent meningioma in a 45-year-old man was removed. As basic experiment for telesurgery, surgical simulation was also conducted in a rat brain with the operating console transported to a hospital 40 km distant from the University. FINDINGS: Opening of the sylvian fissure and third ventriculostomy were accurately performed. Tumour removal in a patient with recurrent meningioma was safely achieved. Surgical simulation in the rat brain was accurately and correctly carried out, operated on from a hospital 40 km distant. CONCLUSIONS: The NeuRobot, telecontrolled micromanipulator system, can be used as a tool for less invasive neurosurgery.

Animals↗

Role of antinuclear antibodies in experimental and clinical liver transplantation.

OBJECTIVE: We recently reported that autoreactive antibodies (Abs) against nuclear histone H1 was transiently induced at an early phase after orthotopic liver transplantation (OLT) in a tolerogenic rat OLT model and possessed immunosuppressive activity. It was also reported that nuclear antigen, high-mobility group box 1 (HMGB1) protein was one of the initiators of the immune reaction. The present study sought to evaluate the role of antinuclear Abs in experimental and clinical liver transplantation. MATERIALS AND METHODS: We prepared 3 animal models: natural tolerance model (DA liver into PVG); acute rejection model (DA liver into LEW); and drug-induced tolerance model (acute rejection model + cyclosporine [CsA]). In addition, we examined clinical samples, including 1 drug-free patient, to measure the antihistone H1/HMGB1 titers at various times after OLT. RESULTS: In a natural tolerance model, antihistone H1 and HMGB1 Ab was induced during the rejection and the tolerance induction phases, respectively. Those Ab responses were also confirmed in a drug-induced tolerance model, whereas no such responses were shown in an acute rejection model. In our clinical drug-free patient, antihistone H1/HMGB1 titer was significantly higher after cessation of CsA than that in healthy volunteers. CONCLUSIONS: Antinuclear Ab is actively expressed in accordance with overcoming rejection episodes with subsequent tolerance induction in both a natural tolerance model and a drug-induced tolerance model. We also observed a similar tendency in our clinical drug-free patient. These results suggested that antinuclear Abs may be useful markers to determine the timing to withdraw immunosuppressants.

Animals↗

Histone H1 vaccine therapy for overcoming acute rejection in experimental organ transplantation.

OBJECTIVE: In a rat tolerogenic orthotopic liver transplantation (OLT) model, the recipient serum (post-OLT serum) shows strong immunosuppressive activity. In our previous reports, we suggested that autoreactive antibody (Ab) against histone H1 is a major immunosuppressive factor in this serum. The present study sought to determine whether up-regulation of anti-histone H1 Ab by histone H1 vaccination led to tolerance. MATERIALS AND METHODS: Using mixed lymphocyte reactions (MLR) and heterotopic heart transplantations (HHT), the alloreactive T-cell responses and allograft survivals of histone H1-immunized rats were compared with those of control rats. Cytokine and cellular profiles were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. RESULTS: The alloreactive T-cell response of histone H1-immunized rats was significantly lower than that of control rats, although there was no difference in nonspecific T-cell activation between the 2 groups. The allograft survival of histone H1-immunized rats was significantly prolonged after HHT. The major histocompatibility complex (MHC) class II and CD25 molecules of histone H1-immunized rats were significantly down-regulated compared with those of control rats. Moreover, the serum cytokine profile was modified by the immunization with histone H1. CONCLUSIONS: These results suggest that histone H1 vaccination of transplant recipients leads to the production of immunosuppressive factors and the modification of cytokine/cellular profiles.

Animals↗

Intraperitoneal injection of oxygenated perfluorochemical improves the outcome of intraportal islet transplantation in a rat model.

A 50% to 75% early graft loss upon engraftment has been suggested to in intraportal islet transplantation (IPIT). Hypoxia in the portal vein contributes to graft loss in immediately posttransplantation. Herein we examined the effect on the outcome of IPIT of intraperitoneal oxygenated perfluorochemical (PFC) as an oxygen carrier. Isolated Lewis rat islets were transplanted into the portal vein of a chemically induced diabetic syngeneic rat. First, 1500 IEQ was determined to be the optimal dose in this study. When oxygenated PFC (group 1) was intraperitoneally injected following IPIT of 1500 IEQ, the success rate of transplantation was 5/6, in contrast to 1/6 when PFC with no oxygen was injected (group 2) and 1/6 in IPIT without PFC, respectively. The area under the glucose profile curve on intraperitoneal glucose tolerance tests on posttransplant day 28 in group 1 was significantly smaller than that for group 2. In conclusion, intraperitoneal oxygenated PFC improved the outcome of IPIT.

Animals↗

Serum amiodarone and desethylamiodarone concentrations following nasogastric versus oral administration.

OBJECTIVE: Hospitalized patients unable to ingest anything by mouth require nutritional support by enteral feeding and administration of drugs through a nasogastric tube inserted into the digestive tract. Nasogastric administration of amiodarone may not always be equivalent to oral administration of amiodarone. METHODS: We collected 162 observations of serum amiodarone and desethylamiodarone metabolite concentrations from 93 patients within 60 days of starting treatment with amiodarone. Eight patients were given the drug nasogastrically and 85 patients, orally. The two groups, were compared in terms of their serum concentration/(dose/weight) (C/D) value. A ratio of serum amiodarone concentration to serum desethylamiodarone concentration (AMD/DEA) was calculated for each sample. In addition, the percentage drug recovery after nasogastric administration of amiodarone was analysed. RESULTS: Significant differences were observed in C/D values of amiodarone and desethylamiodarone and in AMD/DEA values of patients given amiodarone orally when compared with those given the drug nasogastrically. The C/D values of patients who received their medication nasogastrically were approximately 30% of the C/D values of patients who received their medication orally. Approximately 70% of the drug was recovered after it had passed through the nasogastric tube. CONCLUSIONS: To achieve similar concentrations, an approximately 3-fold increase in dosage of amiodarone was required when patients were given the drug nasogastrically rather than orally. This suggests that the absorption of amiodarone following nasogastric administration is poor when compared with oral administration. Therapeutic drug monitoring is necessary to optimize dose particularly during the early stages of amiodarone therapy.

Administration, Oral↗

Intrapatellar tendon lipoma with chondro-osseous differentiation: detection of HMGA2-LPP fusion gene transcript.

A 54 year old man developed an unusual lipoma in the patellar tendon, consisting of a fibro-adipose component and a chondro-osseous component. The fibro-adipose component contained mature adipocytes, lipoblasts, and fibroblasts; the chondro-osseous component showed typical endochondral bone formation. Molecular analysis showed that the identical HMGA2-LPP fusion transcript-characteristic of lipoma, parosteal lipoma, and pulmonary chondroid hamartoma-was detectable in the both components.

Adipogenesis↗