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Biomedical subjects

M Fujita

Publications and source records attributed to M Fujita.

At least 55 records · Page 3Linked to original sources
PubMed2004

Retinoic acid fails to reverse emphysema in adult mouse models.

BACKGROUND: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. METHODS: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-alpha transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. RESULTS: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-alpha transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-alpha transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. CONCLUSIONS: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.

Animals↗
PubMed2004

Protein C inhibitor as an anti-disseminated intravascular coagulation agent--mechanism and modification.

Gram-negative sepsis is associated with disseminated intravascular coagulation (DIC) due to endothelial damage, which is induced by inflammatory mediators released from phagocytes activated by lipopolysaccharide (LPS). DIC is a systemic hemorrhagic syndrome, which results from the consumption of coagulation factors for the formation of multiple thrombi in the systemic microvessels; it is associated with multiple organ failure. Therefore, not only the systemic activation of coagulation but also the inflammatory response has been perceived as the therapeutic target for DIC in sepsis. We gave attention that protein C inhibitor (PCI) acts as an inhibitor of both plasma kallikrein and thrombin, which are known to act not only as procoagulant proteases but also as chemotactic factors toward phagocytes. Then, we hypothesized that PCI possibly acts as an anti-DIC agent rather than an inhibitor of the protein C anticoagulant pathway under the pathophysiology of DIC, accompanied by the decrease in the thrombomodulin expression on endothelial cells. Our studies have suggested that PCI purified from human urine (uPCI) improves the pathophysiology of DIC through the inhibition of activities of plasma kallikrein and thrombin, and the activities of PCI are regulated by N-glycans. This review introduces the anti-DIC action of PCI and about the modification of N-glycosylation site(s) of PCI to heighten the value of PCI as an anti-DIC agent.

Animals↗
PubMed2003

Vascular anatomy for right colon lymphadenectomy.

Since the superior mesenteric artery (SMA) mostly originates on the left side of the superior mesenteric vein (SMV), the ileocolic artery (ICA) and the right colic artery (RCA) cross the SMV. Understanding the three-dimensional relation of these vessels is important for dissecting these arteries to their origin. Hence, we conducted a study of the vascular anatomy of the right colon in 27 cadavers. The RCA was separate from the SMA in eight cases (30%). The RCA passed the SMV either anteriorly (5 cases, 63%) or posteriorly (3 cases, 38%). In seven (88%) of these eight cases, the ICA was posterior to the SMV. The ICA was identified in all 27 cases, and passed the SMV anteriorly in nine cases (33%) and posteriorly in 18 cases (67%). Thus, the ICA and the RCA may pass on either side of the SMV. The surgeon must dissect the arteries with the SMV, being aware of both possibilities.

Aged↗
PubMed2003

Fermi-liquid ground state in the n-type Pr(0.91)LaCe(0.09)CuO(4-y) copper-oxide superconductor.

We report nuclear magnetic resonance studies on the low-doped n-type copper-oxide Pr(0.91)LaCe(0.09)CuO(4-y) (T(c)=24 K) in the superconducting state and in the normal state uncovered by the application of a strong magnetic field. We find that when the superconductivity is removed the underlying ground state is the Fermi liquid state. This result is at variance with that inferred from previous thermal conductivity measurement and appears to contrast with that in p-type copper oxides with a similar doping level where high-T(c) superconductivity sets in within the pseudogap phase. The data in the superconducting state are consistent with the line-node gap model.

Journal Article↗
PubMed2003

Commensurate spin dynamics in the superconducting state of an electron-doped cuprate superconductor.

We report neutron scattering studies on two single crystal samples of the electron-doped (n-type) superconducting (SC) cuprate Nd2-xCexCuO4 (x=0.15) with T(c)=18 and 25 K. Unlike the hole-doped (p-type) SC cuprates, where incommensurate magnetic fluctuations commonly exist, the n-type cuprate shows commensurate magnetic fluctuations at the tetragonal (1/2 1/2 0) reciprocal points both in the SC and in the normal state. A spin gap opens up when the n-type cuprate becomes SC, as in the optimally doped p-type La2-xSrxCuO4. The gap energy, however, increases gradually up to about 4 meV as T decreases from T(c) to 2 K, which contrasts with the spin pseudogap behavior with a T-independent gap energy in the SC state of p-type cuprates.

Journal Article↗
PubMed2003

Detection of single nucleotide polymorphism (SNP) controlling the waxy character in wheat by using a derived cleaved amplified polymorphic sequence (dCAPS) marker.

We investigated a single nucleotide polymorphism (SNP) in the Wx-D1 gene, which was found in a mutant waxy wheat, and which expressed the Wx-D1 protein (granule-bound starch synthase I) as shown by immunoblot analysis. We also assayed starch synthase activity of granule-bound proteins. Using 22 doubled-haploid (DH) lines and 172 F(5) lines derived from the wild type x the mutant, we detected SNP via a PCR-based (dCAPS) marker. Amplified PCR products from Wx-D1 gene-specific primers, followed by mismatched primers designed for dCAPS analysis, were digested with the appropriate restriction enzyme. The two alleles, and the heterozygote genotype were easily and rapidly discriminated by gel-electrophoresis resolution to reveal SNP. All progeny lines that have the SNP of the mutant allele were waxy. Integrating the results of dCAPS analysis, immunoblot analysis and assays of starch synthase activity of granule-bound proteins indicates that the SNP in the Wx-D1 gene was responsible for its waxy character. This dCAPS marker is therefore useful as a marker to introduce the mutant allele into elite breeding lines.

Alleles↗
PubMed2003

Phase diagram of La2-xSrxCuO4 probed in the infared: imprints of charge stripe excitations.

While there is increasing evidence for antiferromagnetic (AF) ordering in the Cu-O planes of high-T(c) superconductors, either static or fluctuating, there is no direct evidence so far for the charge stripes that should separate the AF domains. By investigating the optical response of La2-xSrxCuO4 for 0<or=x<or=0.26 and 30<or=T<or=295 K, we identify strong far infrared peaks whose energy, width, and intensity are consistent with a scenario of charge stripe dynamics in the Cu-O planes.

Journal Article↗
PubMed2003

Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma.

Allergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1-promoting cytokine, interleukin-12, is capable of inhibiting the T helper 2-driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin-12 actions are unclear. The anti-allergic response to interleukin-12 is only partially dependent on interferon-gamma, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti-allergic action of interleukin-12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin-12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin-12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase-mediated deoxyribonucleoside triphosphate nick end-labelling. Administration of interleukin-12 reduced ovalbumin-induced pulmonary eosinophilia (P < 0.01) and CD4+ T cell infiltration (P < 0.01). Moreover, treatment with interleukin-12 shortly after ovalbumin inhalation resulted in both increased interferon-gamma production (P < 0.01) and enhanced apoptosis of CD4+ T cells in allergic airway infiltrates (P < 0.05). These results suggest that the beneficial effects of interleukin-12 in asthma may include enhancement of apoptosis of CD4+ T cells in airways.

Animals↗
PubMed2003

Head and neck cancer arising after endoscopic mucosal resection for squamous cell carcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: It is well known that patients with head and neck cancer often have synchronous or metachronous squamous cell carcinoma of the esophagus. However, the prevalence of subsequent head and neck cancer in patients with early-stage esophageal cancer is still unknown. The aims of this study were to analyze the frequency of metachronous head and neck cancer after endoscopic mucosal resection (EMR) for esophageal cancer and to investigate whether minute iodine-unstained areas, often associated with squamous cell carcinomas, would be an index for metachronous head and neck cancer. PATIENTS AND METHODS: 99 patients with esophageal squamous cell carcinoma who underwent EMR were studied. Based on the iodine-staining pattern at initial EMR, they were categorized into those with uniform (group U) and scattered (group S) types of background mucosa. Patients were monitored endoscopically and otolaryngologically (group U, median 46 months, range 12-83 months; group S, median 44 months, range 13-80 months). RESULTS: In total, 5/99 patients (5.1 %) were found to have metachronous head and neck cancer during the follow-up, including 4/20 patients (20 %) in group S. In three cases laryngeal or hypopharyngeal cancer was found by endoscopic examination. The cumulative proportion of metachronous head and neck cancer-free subjects was significantly lower in group S than group U (P = 0.0007). CONCLUSIONS: Among patients who undergo EMR for esophageal carcinoma, those with scattered-type iodine staining of the background mucosa have an increased risk of metachronous head and neck cancer, and should therefore be closely observed. Careful endoscopic observation led to early detection of laryngeal and hypopharyngeal cancer.

Aged↗
PubMed2003

[Radioulnar impingement after distal ulnar resection and ulnar head hemiresection interposition arthroplasty (Bowers procedure). An experimental biomechanical study].

Resection of the distal ulna (Darrach operation) and the ulnar head hemiresection interposition arthroplasty (Bowers procedure) are common methods of treating the arthrotic distal radioulnar joint (DRUJ). The purpose of this study was to evaluate the dynamic effects of both the Bowers operation and the resection of the distal ulna on radioulnar impingement and dorsal-palmar displacement and to compare their biomechanical performances. With a dynamic forearm simulator forearm rotation was performed with simultaneous loading of relevant muscles. Torque along the forearm axis was generated by simulated muscle action with loading of the relevant tendons while the wrist was constrained to prescribed ranges of motion. The instability of the radius relative to the ulna was evaluated using displacement data of digitized landmarks in an ulnar coordinate system. Seven fresh-frozen cadaver upper extremities were used. Resection of the distal ulna created a significant instability of the forearm with movement of the radius ulnarly. Anteroposterior translations in each loading condition could be detected as well but the magnitude of displacement was little and less predictable. The results of the Bowers operation demonstrated significantly less instability compared with the Darrach results. Our data demonstrates that the dynamic behavior of the Bowers procedure is superior to the mechanical performance of complete resection of the distal ulna.

Arthroplasty↗
PubMed2003

Assessment of the internal effective dose of workers independent of inhaled particle size (II).

For 60Co (Type S) and 54Mn (Type M), for which the whole-body content can be measured, it is possible to minimise the errors of the estimated effective doses caused by uncertainty of the activity median aerodynamic diameter (AMAD) by assuming the AMAD to be 5 microm and by measuring the body content on day 5 after inhalation. For the radionuclides to be measured in the lung content, e.g. 239Pu (Type S), it may be necessary to estimate the AMAD, because the lung burdens on any day are not always proportional to the whole-body content which reflects the effective doses. There is no problem in assuming the AMAD to be 5 microm for external counting and for urinalysis of Type F compounds, because of the rapid absorption of such compounds into the blood and the same biokinetics. The breathing rate is assumed to be 1.2 m3 h(-1).

Absorption↗
PubMed2003

Age-related changes in brain regional activity during chewing: a functional magnetic resonance imaging study.

Age-related changes in mastication-induced brain neuronal activity have been suggested. However, in humans, little is known about the anatomical regions involved. Using fMRI during cycles of rhythmic gum-chewing and no chewing, we have examined the effect of aging on brain regional activity during chewing in young adult (19-26 yrs), middle-aged (42-55 yrs), and aged (65-73 yrs) healthy humans. In all subjects, chewing resulted in a bilateral increase in the BOLD signals in the sensorimotor cortex, cerebellum, thalamus, supplementary motor area, and insula, and a unilateral increase in the right prefrontal area. In the first three regions, the signal increases were attenuated in an age-dependent manner, whereas, in the right prefrontal area, the converse was seen. The remaining two regions showed no significant differences with ages. These results indicate that chewing causes regional increases in neuronal activity in the brain, some of which are age-dependent.

Adult↗
PubMed2003

Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias.

Lung epithelial cells are a primary target for reactive oxygen species (ROS). ROS can cause oxidative deoxyribonucleic acid modification, such as 8-hydroxy-deoxyguanosine (8-OHdG). A human homologue of the MutT protein (hMTH1) prevents this modification. Mitochondria are the most important cellular source of ROS and may be susceptible to oxidative damage. The purpose of this study is to investigate oxidative stress and mitochondrial damage in lung epithelial cells from idiopathic interstitial pneumonias (IIPs). The authors analysed 8-OHdG, hMTH1, and mitochondrial proteins on lung specimens from 13 patients with IlPs consisted of eight patients with usual interstitial pneumonia and five patients with nonspecific interstitial pneumonia using Western blot analysis and immunohistochemistry. Immunoreactivity for 8-OHdG and hMTH1 was significantly increased in the lung epithelial cells from patients with IIPs compared with controls. The expression of hMTH1 was localised in the nuclear and cytoplasmic, but not the mitochondrial, fraction of lung homogenates. Immunoreactivity for mitochondrial protein and cytochrome c oxidase complex subunit IV was increased in the lung epithelial cells from patients with IIPs compared with controls. The current study concludes that oxidative stress may participate in epithelial cell damage in idiopathic interstitial pneumonia, and that increased mitochondrial mass may associate with increased reactive oxygen species production in idiopathic interstitial pneumonia.

Blotting, Western↗
PubMed2003

Ovarian and hormonal response of female goats to active immunization against inhibin.

This study was conducted to evaluate the effect of active immunization against inhibin on hormonal levels and the ovulation rate in goats. Ten adult Shiba goats (Capra hircus) in two groups were used in this study. The first group was injected with inhibin vaccine (immunized, n=5) and the second group was injected with Freund's adjuvant (control, n=5) followed by three booster injections at 4-week intervals. After the third booster injection, three consecutive periods of oestrus were induced using prostaglandin F(2alpha) at intervals of 11 days. Blood samples were collected at 2-6 h intervals and the ovaries were monitored using B-mode ultrasonography. All inhibin-immunized goats generated antibodies that bound (125)I-labelled bovine inhibin and their FSH concentrations were significantly higher than corresponding values in the control group. Also, inhibin-immunized goats had significantly higher preovulatory oestradiol-17beta (P<0.01) and higher concentrations of progesterone in the luteal phase (P<0.05). Immunization of goats against inhibin resulted in a significant (P<0.01) increase in ovulation rate (control: 1.7+/-0.3 vs immunized: 7.6+/-1.1). These results demonstrate that active immunization against inhibin enhances ovarian follicular development and ovulation rate by promoting an increase in pituitary FSH secretion. Therefore, immunization against inhibin may be a useful alternative to the conventional approach of superovulation in goats.

Animals↗
PubMed2003

Effects of passive immunization of goats against inhibin on follicular development, hormone profile and ovulation rate.

This study was conducted to investigate the effect of immunoneutralization against endogenous inhibin on FSH secretion and ovulation rate, with the aim of developing a new superovulation method using inhibin antiserum in goats. Two groups of goats received an i.v. injection of either 10 ml normal goat serum (control; n = 6) or 10 ml inhibin antiserum developed against [Tyr(30)]-inhibin alpha (1-30) (n = 6) 48 h before treatment with prostaglandin F(2alpha) (PGF(2alpha)). Blood samples were collected at 6 h intervals and ovaries were examined each day using a B-mode ultrasound scanner equipped with a 7.5 MHz transducer during the experimental period. Immunization against inhibin resulted in a four- to fivefold increase (P < 0.01) in plasma concentrations of FSH. After luteolysis, plasma concentrations of oestradiol increased markedly to reach a preovulatory peak, which was about two times higher (P < 0.01) than that of the controls. The treatment was accompanied by a significant increase in the total number of follicles of > or = 3 mm in diameter at 24 (8.2 +/- 0.4 in inhibin antiserum group versus 4.8 +/- 0.3 in control group) and 96 h later (13.5 +/- 1.0 in inhibin antiserum group versus 5.3 +/- 0.6 in control group). The ovulation rate was significantly (P < 0.01) higher in goats treated with inhibin antiserum (4.2 +/- 0.5; n = 6) than in control goats (1.8 +/- 0.3; n = 6). These results indicate that inhibin is an important factor in the regulation of FSH secretion in goats and demonstrate that passive immunization against inhibin at 48 h before treatment with PGF(2alpha) induces the development of more follicles and increases ovulation rate. Thus, inhibin antiserum treatment may be an alternative to the use of exogenous gonadotrophins for induction of superovulation in goats.

Animals↗
PubMed2002

DNA methylation and histone deacetylation associated with silencing DAP kinase gene expression in colorectal and gastric cancers.

Death-associated protein kinase is a positive regulator of programmed cell death induced by interferon gamma. To investigate the role of epigenetic inactivation of death-associated protein kinase in gastrointestinal cancer, we examined the methylation status of the 5' CpG island of the death-associated protein kinase gene. Methylation of the 5' CpG island was detected in 3 of 9 colorectal and 3 of 17 gastric cancer cell lines, while among primary tumours, it was detected in 4 of 28 (14%) colorectal and 4 of 27 (15%) gastric cancers. By contrast, methylation of the edge of the CpG island was detected in virtually every sample examined. Death-associated protein kinase expression was diminished in four cell lines that showed dense methylation of the 5' CpG island, and treatment with 5-aza-2'-deoxycitidine, a methyltransferase inhibitor, restored gene expression. Acetylation of histones H3 and H4 in the 5' region of the gene was assessed by chromatin immunoprecipitation and was found to correlate directly with gene expression and inversely with DNA methylation. Thus, aberrant DNA methylation and histone deacetylation of the 5' CpG island, but not the edge of the CpG island, appears to play a key role in silencing death-associated protein kinase expression in gastrointestinal malignancies.

Apoptosis Regulatory Proteins↗