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Biomedical subjects

T Tomita

Publications and source records attributed to T Tomita.

At least 19 recordsLinked to original sources
PubMed2006

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet.

Although skin diseases are one of the target diseases for gene therapy, there has been no practical gene transfer method. First, we examined gene transfer efficiency of the spring-powered jet injector, Shima Jet, which was originally developed as a non-needle jet injector of insulin. Local gene expression was about 100 times higher when the luciferase plasmid was transferred by the Shima Jet than by a needle. Gene transfer of beta-galactosidase revealed gene expression in the epidermis. Based on these results, we then examined the potential of gene therapy using the Shima Jet for wound healing. An increase of cellular proliferation of the epidermis and the number of microvessels in the granulation tissue was observed after hepatocyte growth factor (HGF) gene transfer. An increase in blood flow around the wound was observed after prostacyclin synthase (PGIS) gene transfer. Moreover, promotion on wound healing was observed in HGF gene transferred group, and further promotion was observed in combined gene transferred group as assessed by measuring wound area. These results indicate that co-transfer of HGF and PGIS genes by the Shima Jet could be an effective strategy to wound healing.

Animals↗
PubMed2006

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion.

AIMS/HYPOTHESIS: G protein-coupled receptor 40 (GPR40) is abundantly expressed in pancreatic beta cells in rodents, where it facilitates glucose-induced insulin secretion in response to mid- to long-chain fatty acids in vitro. However, GPR40 gene expression in humans has not been fully investigated, and little is known about the physiological and pathophysiological roles of GPR40 in humans. The aim of this study, therefore, was to examine GPR40 expression and its clinical implications in humans. METHODS: GPR40 mRNA expression in the human pancreas, pancreatic islets and islet cell tumours was analysed using TaqMan PCR. RESULTS: GPR40 mRNA was detected in all human pancreases collected intraoperatively. It was enriched approximately 20-fold in isolated islets freshly prepared from the pancreases of the same individuals. The estimated mRNA copy number for the GPR40 gene in pancreatic islets was comparable to those for genes encoding sulfonylurea receptor 1, glucagon-like peptide 1 receptor and somatostatin receptors, all of which are known to be expressed abundantly in the human pancreatic islet. A large amount of GPR40 mRNA was detected in insulinoma tissues, whereas mRNA expression was undetectable in glucagonoma or gastrinoma. The GPR40 mRNA level in the pancreas correlated with the insulinogenic index, which reflects beta cell function (r=0.82, p=0.044), but not with glucose levels during the OGTT, the insulin area under the OGTT curve or the index for the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSIONS/INTERPRETATION: The present study provides evidence for GPR40 gene expression in pancreatic beta cells and implicates GPR40 in insulin secretion in humans.

Adult↗
PubMed2006

Effects of obesity phenotype on fat metabolism in obese men during endurance exercise.

OBJECTIVE: The effects of obesity phenotype on fat metabolism during endurance exercise are unclear. This study aimed to investigate in obese men whether body fat distribution would influence plasma fat availability and oxidation during endurance exercise. DESIGN: Fourteen sedentary men (body mass index (BMI) > 25 kg/m2) were divided into two groups by visceral fat (VF) area: VF obese (VF-Ob) (n = 7, age; 52.0 +/- 2.5 (s.e.) years) and abdominal subcutaneous fat obese (SF-Ob) (n = 7, age; 57.3 +/- 2.8 (s.e.) years). All participants performed stationary cycling exercise for 60 min at 50% of peak oxygen uptake. MEASUREMENTS: Blood and respiratory gas samples were taken for analysis of hormone, metabolite and substrate oxidation in each participant at rest and during exercise. RESULTS: There is a significant group x time interaction in the plasma concentration of free fatty acid (FFA) (P < 0.05) and glycerol (P < 0.05) during the exercise bout. In addition, total plasma concentration of FFA (area under the curve) was 59.2% higher in VF-Ob compared with SF-Ob men during endurance exercise (1.99 +/- 0.24 and 1.25 +/- 0.13 mEq/l/min, respectively; P < 0.05). Total plasma concentration of glycerol (area under the curve) was 102.3% higher in VF-Ob than SF-Ob men during the exercise (69.6 +/- 12.5 and 34.4 +/- 5.1 mg/dl/min, respectively; P < 0.05). However, fat oxidation was not different throughout the exercise between VF-Ob and SF-Ob men (176.5 +/- 25.7 and 183.0 +/- 12.8 kcal/60 min, respectively). CONCLUSION: During moderate endurance exercise, plasma fat availability may be higher in men with VF obesity compared to men with SF obesity. However, total fat oxidation is similar between obesity phenotype.

Analysis of Variance↗
PubMed2006

NFkappaB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts.

The transcription factor, nuclear factor-kappa B (NFkappaB), is believed to play a pivotal role in osteoclast formation. In this study, we focused on NFkappaB decoy oligodeoxynucleotides (ODN) as a new therapeutic strategy to attenuate osteoporosis. Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts formed in mononuclear cells including osteoclast precursors from neonatal rabbit bone marrow were increased in the presence of 1,25-dihydroxyvitamin D3, whereas transfection of NFkappaB decoy ODN decreased the number of TRAP-positive cells and attenuated RANKL and M-CSF-induced osteoclast formation. NFkappaB decoy ODN also inhibited the activity of osteoclasts, as assessed by pit formation. In rat ovariectomized model of estrogen deficiency, continuous administration of NFkappaB decoy ODN attenuated the increase of TRAP activity, accompanied by a significant increase in calcium concentration in tibia and femur and decrease in urinary deoxypyridinoline. In additional osteoporosis model using vitamin C-deficient rat, inhibition of NFkappaB by decoy ODN dramatically improved the bone length, weight, density as assessed by dual-energy X-ray absorptiometry. Overall, inhibition of NFkappaB by decoy strategy prevented osteoporosis through the inhibition of bone resorption. Targeting of NFkappaB might be potential therapy in various bone metabolic diseases.

Absorptiometry, Photon↗
PubMed2006

Enhancement of the critical current density of YBa2Cu3Ox superconductors under hydrostatic pressure.

The dependence of the critical current density Jc on hydrostatic pressure to 0.6 GPa is determined for a single 25 degrees [001]-tilt grain boundary in a bicrystalline ring of nearly optimally doped melt-textured YBa2Cu3Ox. Jc is found to increase rapidly under pressure at +20%/GPa. A new diagnostic method is introduced (pressure-induced Jc relaxation) which reveals a sizable concentration of vacant oxygen sites in the grain boundary region. Completely filling such sites with oxygen anions should lead to significant enhancements in Jc.

Journal Article↗
PubMed2006

Development of a magnetizing stage for in situ observations with electron holography and Lorentz microscopy.

A magnetizing stage, by which approximately horizontal magnetic fields can be applied to thin-foiled specimens, has been developed so that magnetization process can be observed in situ with electron holography and Lorentz microscopy. It is possible to apply magnetic field up to 200 Oe without serious image distortion by utilizing the magnetizing stage, beam-deflection-back coils and a magnetically shielded objective lens. The devised system can be used to studies of magnetization processes in many soft magnets.

Letter↗
PubMed2006

Effects of in ovo exposure to imazalil and atrazine on sexual differentiation in chick gonads.

We examined the effects of atrazine and imazalil, 2 commonly used pesticides, on sexual differentiation in chickens. Atrazine and imazalil were injected into fertile eggs on d 0. At hatching, sex genotype and phenotype were determined. Gonads were stereomicroscopically and histologically observed. In ovo exposure of atrazine (0.01 to 3 mg/egg) did not influence hatchability, whereas imazalil exposure (2 mg/egg) inhibited hatchability. The sex genotype matched the sex phenotype in controls, atrazine, and imazalil-exposed groups. In control females, the right gonad was regressed at hatching. Regression of the right gonad, however, was inhibited following atrazine and imazalil exposure. In atrazine-exposed female chicks, the left gonads had normal ovary structures, and the remaining right gonads had ovary medulla-like structures. In imazalil-exposed females, some left gonads had an ovary medulla-like structure without the cortex as well as tubules, and the right gonad had testis-like structures. There was no change in male gonads at hatching following atrazine and imazalil exposure. Aromatase activity of the left gonad from female chicks was not changed by any concentration of atrazine exposure. These results suggest that atrazine and imazalil inhibit regression of the right gonad in female chicks, although it is not clear whether the remaining right gonad has aromatase activity. In ovo exposure to atrazine influences sexual differentiation of the ovary by different mechanisms from imazalil, possibly by the induction of aromatase in the right gonad, whereas it is confirmed that imazalil inhibits in vitro aromatase activity in the chick ovary. The results indicated that in ovo exposure to imazalil inhibits sexual differentiation of the ovary by inhibiting aromatase activity.

Animals↗
PubMed2006

The thickness of the roof of the glenoid fossa in the temporomandibular joint: relationship to the MRI findings.

OBJECTIVES: The purpose of this study was to clarify the relationship between the thickness of the roof of the glenoid fossa (RGF) and magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) disorders (TMDs). METHODS: Eighty-seven patients with symptoms and indications of TMD in one or both TMJs were referred for MRI. Cone-beam CT (3DX) was used to measure the thickness of the RGF at its thinnest point. Linear measurements were made three times on the monitor by three separate investigators and the mean values obtained were used for the statistical analyses. RESULTS: The joints were categorised as normal (70 joints), anterior disc displacement with reduction (ADWR; 53 joints) or anterior disc displacement without reduction (ADWOR; 51 joints). The joint disorders were also categorised into the following subgroups: with osteoarthritis (OA) (21 joints), without OA (153 joints), with disc deformation (33 joints), without disc deformation (141 joints), with joint effusion (JE) (61 joints) and without JE (113 joints). The average minimum thickness of the RGF was 0.85 mm for normal joints, 0.90 mm with ADWR, 0.93 mm with ADWOR, 0.99 mm with OA, 0.87 mm without OA, 0.87 mm with disc deformation and 0.89 mm without disc deformation. There was no significant difference between these figures. There was a significant difference in the thickness of the RGF with (0.97 mm) and without (0.84 mm) JE. CONCLUSIONS: These results suggest that RGF thickness is influenced by JE, but is unaffected by disc position and configuration.

Adolescent↗
PubMed2005

Comparison between mobile-bearing and fixed-bearing knees in bilateral total knee replacements.

The purpose of this study was to compare mid-term results of mobile-bearing and fixed-bearing in bilateral total knee arthroplasty (TKA). Twenty-two patients underwent bilateral TKA with a mobile-bearing prosthesis (Rotaglide, Corin, UK) on one side and a fixed-bearing prosthesis (NexGen-CR, Zimmer, USA) on the other. There were 21 female patients, and in 18 patients, the diagnosis was rheumatoid arthritis. The average age was 59.6 (35-78) years. In all procedures, the posterior cruciate ligament was retained and patella re-surfaced. The average follow-up in the mobile-bearing group was 98 (79-107) months and 96 (79-107) months in the fixed-bearing group. At the final follow-up, the knee score was 91.8 points and 91.1 points, respectively, and the function score 65.5 points. The range of motion was similar in the two groups (1.1-106.9 degrees; 0.4-106.9 degrees). Five patients favoured the fixed-bearing prosthesis, but 16 found no difference. In patients with bilateral TKA, there was no difference in the short-term result between mobile-bearing and fixed-bearing prostheses.

Adult↗
PubMed2005

Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population.

BACKGROUND: Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-gamma and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis. METHODS: Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at -607C/A and -137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls. RESULTS: In UC, the -137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The -137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (-607A, -137C), which had a lower promoter activity and IFN-gamma mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences. CONCLUSIONS: IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC.

Adolescent↗
PubMed2004

Comparison of the activities of multinucleated bone-resorbing giant cells derived from CD14-positive cells in the synovial fluids of rheumatoid arthritis and osteoarthritis patients.

OBJECTIVE: To investigate the morphology and function of multinucleated bone-resorbing giant cells derived from CD14-positive cells in the synovial fluids (SF) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: CD14-positive cells were obtained by magnetic-activated cell sorting of primary cultures of mononuclear cells from the SF. Multinucleated bone-resorbing giant cells were induced from the CD14-positive cells in the presence or absence of cytokines. We examined various characteristics, including osteoclast markers, fusion index and bone-resorption activities of the multinucleated giant cells. RESULTS: Multinucleated giant cells were induced from the CD14-positive cells in the SF of the RA and OA patients by the addition of interleukin (IL)-3, IL-5 and IL-7, or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. These multinucleated giant cells were positive for tartrate-resistant acid phosphatase (TRAP), carbonic anhydrase II, actin, vitronectin receptor and the calcitonin receptor. However, the average values for the number of nuclei, fusion index and bone-resorption functions of the SF cells from the RA patients were significantly higher than those derived from the OA patients. CONCLUSION: These results suggest that the induction and activities of multinucleated bone-resorbing giant cells may play a pivotal role in bone destruction, and that these processes may be enhanced significantly in RA patients.

Adult↗
PubMed2004

Surgical anatomy and efficient modification of procedures for selective extradural anterior clinoidectomy.

OBJECTIVE: The surgical anatomy of structures surrounding the anterior clinoid process (ACP) was examined in 39 cadavers to enable safe performance of selective extradural anterior clinoidectomy. METHODS: The lateral portion of the optic canal (OC) at the end of the orbit was defined as point A, and the lateral margin of the dural insertion into the superior orbital fissure (SOF) as B. A vertical line from A to the lateral margin of the ACP was assumed to define a crossing, defined as C. Distances between A and B, C and B, and C and A were measured. The length and width of OC and the optic strut were also measured. RESULTS: The mean distances between A and B, C and B, and C and A were 11.8, 8.9 and 6.3 mm, respectively. The mean length and width of OC were 8.9 and 5.7 mm, and those of the optic strut 5.4 and 2.4 mm, respectively. CONCLUSION: We propose a modified, efficient procedure for selective extradural anterior clinoidectomy, as follows. Drilling is started from the point approximately 9 mm posterior to the lateral margin of the dural insertion into the SOP, and pointed medially in the direction with a right angle to the lateral margin of the ACP. After drilling about 6 mm to reach the lateral border of the OC, unroofing of the OC is carried out to remove the ACP en bloc by fracturing of the optic strut. Using the present procedure, the distance of drilling of the lesser wing of the sphenoid bone is minimized.

Adult↗
PubMed2004

Two amino acid substitutions in acetylcholinesterase associated with pirimicarb and organophosphorous insecticide resistance in the cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae).

The complete coding sequences of two acetylcholinesterase (AChE) genes, Ace1 (orthologous to Drosophila Ace) and Ace2 (paralogous to Ace), from the cotton aphid (Aphis gossypii) were identified and sequences from carbamate resistant and susceptible strains compared. No change in the amino acid sequences was found in Ace1, while two amino acid substitutions, Ser431Phe and Ala302Ser, were detected between resistant and susceptible strains in Ace2. The position of Ser431Phe corresponds to one of fourteen aromatic residues lining the active site gorge and is located in the acyl pocket. Ala302Ser is located at one of the three residues which form the oxyanion hole in the active site of AChE. The Ser431Phe and Ala302Ser substitutions may play a role in pirimicarb and organophosphate resistance, respectively.

Acetylcholinesterase↗
PubMed2003

Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair.

Localization and expression of mRNAs for sonic hedgehog (Shh) at a fracture site in the early phase postfracture were investigated by in situ hybridization and reverse transcription and polymerase chain reaction (RT-PCR). A closed fracture was made in the midshaft of the right tibia of 5-week-old ICR mice, and fractured sites were harvested prefracture (day 0) and on days 2 and 12. In situ hybridization revealed that transcripts for Shh were not detected on day 0, but they were detected in proliferating callus-forming cells in the periosteum and the surrounding tissue, and in the medullary cavity prior to apparent new cartilage and bone formation. Gli 1 (a signaling mediator for Shh) and bone morphogenetic protein-4 transcripts were colocalized with those for Shh transcripts on day 2. The RT-PCR showed that Shh mRNA was detected in the PCR product from day 2, but not from days 0 and 12. These findings are the first description about the activation of Shh gene in the early postfracture reaction.

Animals↗
PubMed2003

Neck and abdominal muscle activity during a sniff.

Measurement of sniff nasal inspiratory pressure (SNIP) is now used widely as a simple, non-invasive assessment of global respiratory muscle strength, even though the technique evolved originally from measurements of trans-diaphragmatic pressure (Pdi) that reflect the status of the diaphragm. The relative participation of major respiratory muscles, apart from the diaphragm, in the generation of SNIP is not known. Therefore, we examined the activity during a sniff of both neck and abdominal "accessory" muscles. In seven young adults we implanted fine wire EMG electrodes under direct vision with high-resolution ultrasound into scalene, sternocleidomastoid, trapezius, and transversus abdominis. SNIP was measured during sniffs that were short and sharp, from low to maximal intensity, in both standing and supine postures. Mean maximum SNIP was -105.6cmH2O (SD 32.9) in supine and -94.5cmH2O (26.6) in the standing posture, (difference NS). In every subject, scalene activity appeared even at the lowest SNIP, and increased linearly with increasing SNIP. Sternomastoid activity appeared at higher SNIP levels in three of seven subjects. By contrast, trapezius activity was never present at low SNIP, and appeared in only 2 subjects at maximum SNIP. Sniff abdominal expiratory activity was inconsistent with no activity of transversus in four of seven subjects even at greatest SNIP. Thus, we observed differential activation among these non-diaphragm respiratory muscles during SNIP; while some accessory muscles were very active, others were unlikely to contribute to generation of SNIP. Clinically, this indicates SNIP will be impacted unequally by loss of function of specific respiratory muscles.

Abdominal Muscles↗
PubMed2003

Localization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte.

OBJECTIVES: To examine the localization of bone morphogenetic protein (BMP)-2 mRNA and protein in human osteoarthritic (OA) articular cartilage and osteophyte. DESIGN: Five normal, four growing and 14 OA human cartilage samples, graded histomorphologically by Mankin Score, were studied by in situ hybridization and immunohistochemistry for the expression of BMP-2. RESULTS: BMP-2 mRNA was present in chondrocytes in neonatal growing articular cartilage, but was scarcely present in normal adult articular cartilage. In OA articular cartilage, BMP-2 mRNA and protein were detected in both clustering and individual chondrocytes in moderately or severely damaged OA cartilage. In moderately damaged OA cartilage, BMP-2 mRNA was localized in both upper and middle zone chondrocytes, but was not detected in deep layer chondrocytes. In severely damaged OA cartilage, cellular localization of BMP-2 mRNA was extended to the deep zone. In the area of osteophyte formation, BMP-2 mRNA was intensely localized in fibroblastic mesenchymal cells, fibrochondrocytes, chondrocytes and osteoblasts in newly formed osteophytic tissue. The pattern of BMP-2/4 immunolocalization was associated with that of mRNA localization. CONCLUSIONS: BMP-2 mRNA and BMP-2/4 were detected in cells appearing in OA tissues. BMP-2 was localized in cells of degenerating cartilage as well as osteophytic tissue. Given the negative localization of BMP-2 in normal adult articular cartilage, BMP-2 might be involved in the regenerating and anabolic activities of OA cells, which respond to cartilage damage occurring in osteoarthritis.

Aged↗