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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 19 recordsLinked to original sources

Pulmonary clearance of aerosolized 99mTc-DTPA in sarcoidosis I patients.

AIM: Sarcoidosis frequently affects the lungs of patients. Pulmonary clearance scintigraphy with Technetium-99m-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) aerosol may assess pulmonary involvement of sarcoidosis patients. The study investigated early pulmonary involvement of sarcoidosis I patients by assessing the pulmonary clearance of inhaled (99m)Tc-DTPA aerosol and the character of pulmonary clearance though systemic steroid therapy. METHODS: The pulmonary clearance of (99m)Tc-DTPA aerosol was investigated in 24 patients with suspected stage I sarcoidosis and 20 non-smoking healthy controls over 18 months. The radiological finding was evaluated by chest computed radiography (CR) and high resolution computed tomography (HRCT) and the histological diagnosis was performed by transbronchial lung biopsy and/or Scalen node biopsy. The sarcoidosis I patients with ocular involvement underwent 1 year-systemic steroid therapy and were followed up over totally 18 months. RESULTS: The histological diagnosis was proved in 13 out of the 24 patients that had no lung filed involvement on CR and HRCT. Accelerated pulmonary clearance of (99m)Tc-DTPA was observed in 10 out of the 13 sarcoidosis I patients. Nine out of 13 sarcoidosis I patients underwent systemic steroid therapy due to ocular involvement and the accelerated pulmonary clearance responded to therapy and improved in all of the 9 over 18 months. CONCLUSIONS: Acceleration of (99m)Tc-DTPA pulmonary clearance may be observed in sarcoidosis I patients and the acceleration will respond to systemic steroid therapy. Pulmonary clearance scintigraphy with (99m)Tc-DTPA aerosol may be useful for assessing pulmonary involvement before radiological changes emerge and sarcoidosis I patients with accelerated pulmonary clearance may undergo systemic steroid treatment.

Administration, Inhalation↗

Relationship between porotic changes in alveolar bone and spinal osteoporosis.

Epidemiological studies have shown that post-menopausal women who do not use an estrogen supplement have fewer teeth than those who do. We hypothesized that changes in the dentition of post-menopausal women might be due to alveolar bone alterations by estrogen deficiency. To clarify this, we analyzed the microstructural alveolar bone changes in ovariectomized monkeys and compared these with their lumbar bone mineral density. The % of baseline bone mineral density showed a significant decrease in the ovariectomized group as compared with the controls. The second-molar interradicular septa in ovariectomized monkeys showed a significantly decreased nodes number, cortices number, and an increased structural model index value. More pores were seen in the ovariectomized group at the top of the septa. This study demonstrated that, in such monkeys, estrogen deficiency led to fragility of the trabecular structure of the molar alveolar bone, and such fragility was inversely correlated with lumbar bone mineral density.

Absorptiometry, Photon↗

Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues.

AIM: To examine human beta-defensin-3 (hBD-3) expression in inflamed gastric mucosal tissues or MKN45 gastric cancer cells with or without H. pylori infection for better understanding the innate immune response to H. pylori. METHODS: We used reverse transcription-polymerase chain reactions and immunohistochemistry to examine hBD-3 expression in inflamed gastric mucosal tissues or MKN45 gastric cancer cells with or without H. pylori. Effects of hBD-3 against H. pylori were also evaluated. RESULTS: The mean mRNA expression of hBD-3 in H. pylori-positive specimens was significantly higher than that in H pylori-negative specimens (P = 0.0002, Mann-Whitney). In addition, unlike uninfected samples, 8 of 15 (53.33%) infected mucosal samples expressed hBD-3 protein. H. pylori dose-dependently induced mRNA expression of hBD-3 in MKN45 cells, an effect inhibited by adding anti-toll-like receptor (TLR)-4 antibody. HBD-3 protein completely inhibited H. pylori growth. CONCLUSION: Our results suggest that like hBD-2, hBD-3 may be involved in the pathophysiology of H. pylori-induced gastritis.

Antibodies, Anti-Idiotypic↗

Immunohistochemical co-localization of transient receptor potential vanilloid (TRPV)1 and sensory neuropeptides in the guinea-pig respiratory system.

Electrophysiological studies within the lung have documented the presence of heterogenous groups of afferent fibers composed of Adelta and C-fibers and studies of somatosensory nerves within the skin reveal a complex pattern of distribution of sensory neuropeptides and transient receptor potential vanilloid (TRPV)1 positive nerves. However, the anatomical location of these different subpopulations of nerves within the lung has not been extensively studied. In the present study we have demonstrated that TRPV1 axons represented only a small proportion of the total number of PGP9.5 staining nerves within guinea-pig tracheal epithelium and only half the number of TRPV1 axons was immunopositive for substance P. In contrast, most TRPV1 positive neurones found within guinea-pig intrapulmonary airways were found to co-localize with sensory neuropeptides substance P and calcitonin gene-related peptide within and beneath the epithelium, around blood vessels, within airway smooth muscle and alveoli, indicative of heterogeneity of TRPV1 positive axons throughout the airways. However, in the smooth muscle layer of the trachea there was evidence of substance P and calcitonin gene-related peptide containing nerves that did not stain for TRPV1. We also demonstrated a complete loss of TRVP1 positive axons in the trachea and intrapulmonary airways and associated loss of bronchoconstriction induced by capsaicin, in animals chronically treated with capsaicin. However, some neuropeptide immunoreactive axons remained in the smooth muscle layer of capsaicin-treated animals which could represent the small subset of neuropeptide containing fibers which do not co-localize with TRPV1. We have provided evidence of heterogeneity of TRPV1 positive nerve fibers, including fibers characterized by lack of co-localization with neuropeptides in various regions of the airways and the existence of neuropeptide containing fibers that were not TRPV1 positive in guinea-pigs.

Animals↗

Neurofibromatosis type 1 gene haploinsufficiency reduces AP-1 gene expression without abrogating the anabolic effect of parathyroid hormone.

Approximately 50% of neurofibromatosis type 1 (NF1) patients exhibit skeletal pathology, such as premature osteoporosis or pseudoarthroses. Loss of neurofibromin deregulates Ras signal transduction to affect generation of mitogen-activated protein kinase and Akt, both of which have been implicated in parathyroid hormone (PTH) anabolic mechanisms. Our aim was to determine if loss of neurofibromin impaired the anabolic effect of PTH on bone mass. Nf1 heterozygote (Nf1(+/-)) and wild type (Nf1(+/+)) mice were treated with recombinant human PTH(1-34) or vehicle once daily for 3-28 days. PTH enhanced mRNA expression of c-fos, junB, and fra2 in the distal femur metaphyses of both genotypes; expression of these transcripts was consistently lower in PTH-treated Nf1(+/-) mice. Despite lowered c-fos expression in Nf1(+/-) mice, PTH increased bone mass equivalently in both genotypes by 28 days. Ex vivo, Nf1 heterozygosity was associated with increased inducible osteoclasts in PTH-treated bone marrow cells and impairment of the actin stress fiber and cyclic adenosine monophosphate response to PTH in osteoprogenitors. Lower c-fos expression was previously thought to abrogate PTH responsiveness. Our results suggest crosstalk might occur between Ras signal transduction and the protein kinase A pathway in Nf1(+/-) mice. Ras signal transduction does not appear to be essential for the anabolic actions of PTH on bone. Because PTH was effective in the absence of Nf1, it may offer a useful approach to treat osteoporosis in NF1 patients.

Acid Phosphatase↗

Decreased fidelity in replicating DNA methylation patterns in cancer cells leads to dense methylation of a CpG island.

Cancer cells that have a large number of aberrantly methylated CpG islands (CGIs) are known to have CpG island methylator phenotype (CIMP), and decreased fidelity in replicating methylation patters has been analyzed as an underlying mechanism. First we developed a method to analyze the number of errors in replicating CpG methylation patterns in a defined period. A single cell was expanded into 106 cells, and the number of errors during the culture was measured by counting the deviation from the original methylation patterns. It was shown that methylated status of a CpG site was more stably inherited than unmethylated status, suggesting that the genome is constantly exposed to de novo methylation. Promoter CGIs showed higher fidelities than CGIs outside promoter regions. We then analyzed error rates in two gastric cancer cell lines without CIMP and two with CIMP for five promoter CGIs. Two CIMP(-) cell lines showed error rates smaller than 1.0x10(-3) errors per site per generation (99.90%-100% fidelity) for all the five CGIs. In contrast, AGS cells showed significantly elevated error rates, mainly due to increased de novo methylation, in three CGIs (1.6- to 3.2-fold), and KATOIII cells showed a significantly elevated error rate in one CGI (2.2-fold). Presence of densely methylated DNA molecules was observed only in KATOIII and AGS. These data demonstrated that some cancer cells have decreased fidelity in replicating CpG methylation patterns that underlie CIMP.

Breast↗

Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.

BACKGROUND: In order to establish efficient gammadelta T-cell based tumor immunotherapy, we explored a method to enhance the cytotoxicity of gammadelta T cells against leukemia cells by stimulating gammadelta T cells with type I IFN. METHODS: Gammadelta T cells were expanded from normal PBMC by culturing with zoledronate and a low concentration of IL-2 for 2 weeks. For the activation of gammadelta T cells, gammadelta T cells were cultured with type I IFN (HLBI, IFN-alpha2b and IFN-beta) for 1-3 days. The cytotoxicity of HLBI-activated gammadelta T cells against leukemia cell lines and fresh leukemia cells was evaluated by 51Cr-release assay. RESULTS: Gammadelta T cells, which were expanded and purified with magnetic beads using an anti-gammadelta TCR MAb, were demonstrated to be cytotoxic against leukemia cell lines of both lymphoid and myeloid origin and fresh myeloid leukemia cells. By culturing expanded gammadelta T cells with type I IFN, the expression of the activation marker CD69 was increased and the cytometric bead array showed an elevated production of IFN-gamma by gammadelta T cells. In addition, the cytotoxicity of gammadelta T cells against leukemia cells was definitely enhanced by culturing gammadelta T cells with HLBI. DISCUSSION: The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gammadelta T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated gammadelta T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma.

Antigens, CD↗

[Total anomalous pulmonary venous connection showing an unusual shape of the pulmonary vein successfully repaired in a neonate; report of a case].

A 10-day-old neonate with Darling type Ia of total anomalous pulmonary venous connection is presented. The left pulmonary vein entered the right thoracic cavity behind the right atrium and drained into the innominate vein together with the right lower, middle and upper pulmonary veins. The patient was treated with right-sided approach. The postoperative course was uneventful. To our knowledge, this case is the first successful correction of this subtype of anomaly in Japan.

Cardiac Surgical Procedures↗

Case study of a pregnant woman with decidualized ovarian endometriosis whose preoperative findings suggested malignant transformation.

BACKGROUND: Because both decidualization and malignant transformation of endometriosis are characterized by mural nodules on the wall of the cyst, the preoperative differential diagnosis is reportedly difficult. CASE: A 31-year-old woman was referred to our hospital at ten weeks of gestation. Sonographic examination revealed an intrauterine gestational sac and ovarian endometrial cyst. At 21 weeks of gestation, characteristic findings associated with malignant transformation of ovarian endometriosis were seen on color-flow Doppler sonography and contrast magnetic resonance imaging. Under the diagnosis of malignant transformation of ovarian endometriosis, right salpingo-oophorectomy was performed at 22 weeks' gestation. However, histopathologic examination revealed ovarian endometriosis with marked decidual changes but no evidence of malignancy. CONCLUSION: During pregnancy, intracystic vascularized excrescences of an endometrial cyst indicate not only malignant transformation but also decidualization. Thus, the preoperative differential diagnosis is reportedly difficult. However, the present findings of decidualization on magnetic resonance imaging seemed to be slightly different from those of malignant transformation, and therefore, might help distinguish decidualized endometriosis from malignant transformation preoperatively.

Adult↗

[Thoracic surgery for the penetrating lung or tracheal trauma].

Seven cases suffered from a chest trauma (stab wound in 6 and impalement injury in 1) were emergently transferred to our hospital. Open thoracotomy was performed for the intolerable bleeding immediately after admission. Injured lung was treated by lobectomy in 1 patient, lingual segmentectomy in 2, lower basal segmentectomy in 2, partial resection in 4 and direct suture in 2. The penetrating trachea was carefully repaired by direct suture with additional midsternal thoracotomy. To accomplish appropriate partial resection of the injured lung, a metallic straight suction tube inserted into a pulmonary stab wound was retracted and a stapling instrument was applied underneath the suction tube. With the segmentectomy and the partial resection, the volume of the residual lung was maximally saved. As a result, all 7 patients were successfully alive.

Adult↗

[Primary biventricular repair for interrupted aortic arch with left ventricular outflow tract obstruction and tricuspid valve regurgitation; report of a case].

An interrupted aortic arch was diagnosed in a 10-day-old girl weighing 3.3 kg, as was perimembranous ventricular septal defect (VSD) and severe tricuspid valve regurgitation (TR). The subaortic diameter was 3.6 mm and the aortic valve (3.7 mm in diameter) was bicuspid. We chose definitive repair, modified Yasui procedure, because of severe TR and no straddling of mitral valve. In primary biventricular repair, we undertook extended aortic arch anastomosis. Left ventricular outflow tract reconstruction consisted of intracardiac rerouting from the VSD to the pulmonary artery by using expanded-polytetrafluoroethylene (ePTFE) and Damus-Kaye-Stansel (DKS) anastomosis. Right ventricular outflow tract reconstruction was performed by the Rastelli procedure with an ePTFE valved conduit. Moreover, we carried out semicircular annuloplasty for severe TR.

Anastomosis, Surgical↗

The retroperitoneum protects prosthetic graft material from intraperitoneal contamination: an experimental study.

OBJECTIVES: To evaluate the ability of the retroperitoneum to serve as a barrier, against bacterial contamination, between the peritoneal cavity to the retroperitoneal space. METHODS: Seventy rats had a small piece of knitted Dacron graft placed in the retroperitoneal space and 10(6)-10(9) colony forming unit (cfu) Enterococcus faecalis was injected into the peritoneal cavity. In half the retroperitoneal (RP) group, the retroperitoneum was preserved and in the remainder, the open peritoneal (OP) group, needle holes were created. Grafts were harvested after 1, 4, or 7 days and cultured for E. faecalis. A blood sample was collected from three rats in each group for culture before the graft was harvested. RESULTS: Graft infection did not develop in any rat injected with 10(6) or 10(7) cfu in the RP group, while seven out of the 10 graft cultures of the OP group grew E. faecalis (P = 0.003). In rats injected with 10(8) or 10(9) cfu, five out of the 10 graft cultures in the RP group and eight out of 10 in the OP group grew E. faecalis. All blood cultures were negative when the injected bacterial count was 10(7) cfu or less. One out of the three blood cultures was positive at 10(8) cfu, and all were positive at 10(9) cfu. CONCLUSIONS: These results suggest that an intact retroperitroneum acts as a protective barrier against intraperitoneal bacterial contamination, particularly when blood cultures are negative.

Animals↗

Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice.

BACKGROUND AND AIMS: Major histocompatibility complex class II deficient (Aalpha0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aalpha0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aalpha0/0 mice. METHODS: Stomachs from 1-6 month old Aalpha0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aalpha0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Ialpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aalpha0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Spin-torque diode effect in magnetic tunnel junctions.

There is currently much interest in the development of 'spintronic' devices, in which harnessing the spins of electrons (rather than just their charges) is anticipated to provide new functionalities that go beyond those possible with conventional electronic devices. One widely studied example of an effect that has its roots in the electron's spin degree of freedom is the torque exerted by a spin-polarized electric current on the spin moment of a nanometre-scale magnet. This torque causes the magnetic moment to rotate at potentially useful frequencies. Here we report a very different phenomenon that is also based on the interplay between spin dynamics and spin-dependent transport, and which arises from unusual diode behaviour. We show that the application of a small radio-frequency alternating current to a nanometre-scale magnetic tunnel junction can generate a measurable direct-current (d.c.) voltage across the device when the frequency is resonant with the spin oscillations that arise from the spin-torque effect: at resonance (which can be tuned by an external magnetic field), the structure exhibits different resistance states depending on the direction of the current. This behaviour is markedly different from that of a conventional semiconductor diode, and could form the basis of a nanometre-scale radio-frequency detector in telecommunication circuits.

Journal Article↗

Observation of a molecular frame (e, 2e) cross section: an (e, 2e + M) triple coincidence study on H(2).

We report the first experimental results showing transition-specific anisotropy of molecular frame (e, 2e) cross sections. Vector correlations between the two outgoing electrons and the fragment ion have been measured for specific ionization-excitation processes of H2. The results enable us to obtain molecular frame (e, 2e) cross sections for transitions to the 2ssigma(g) and 2psigma(u) excited states of H(2)(+), thereby making stereodynamics of the electron-molecule collisions directly visible.

Journal Article↗

Effect of calcium trisodium DTPA in rats with puncture wound contaminated by 90Y-chloride.

The efficacy of diethylenetriaminepentaacetate calcium trisodium (CaNa(3)DTPA) in a dose of 34.7 micromol kg(-1) as a function of its route of administration was investigated in rats with a puncture wound contaminated by (90)Y-chloride at a concentration of 2.55 MBq kg(-1). Approximately 60% of (90)Y-chloride at a puncture wound was absorbed into the body of rats over 72 h post-puncture and radioactivity in femoral bone increased during the timed-release of (90)Y. Intravenous administration of CaNa(3)DTPA (systemic treatment) at 15 min post-puncture reduced (90)Y at a puncture wound and in bone up to 75.6 and 84.3% of controls, respectively. Direct infiltration of CaNa(3)DTPA into a puncture wound site (local treatment) at 15 min post-puncture diminished radioactivity at the puncture wound and in bone up to 34.9 and 52.5% of controls, respectively. Thus, prompt local treatment may be effective for removing (90)Y from a puncture wound and minimising (90)Y-distribution to bone compared with systemic treatment.

Animals↗

A nucleotide substitution responsible for the tawny coat color mutation carried by the MSKR inbred strain of mice.

"Tawny" is an autosomal recessive coat color mutation found in a wild population of Mus musculus molossinus. The inbred strain MSKR carries the mutation. The causative gene Mc1r(taw) of the tawny phenotype is the second recessive allele at the melanocortin 1 receptor locus and is dominant to the first recessive allele, "recessive yellow" (Mc1r(e)). The Mc1r(taw) gene has six nucleotide substitutions, and its forecasted transcript has three amino acid substitutions (i.e., V101A, V216A, W252C). Though the nucleotide substitutions leading to V101A and V216A exist in various mouse strains, the nucleotide substitution leading to W252C exists in only tawny-colored mice. Thus this substitution is considered to be responsible for the expression of the tawny coat color. The frequency of the allele having this nucleotide substitution was 9.21% in the wild M. m. molossinus population inhabiting Sakai City, Osaka Prefecture, Japan, where the ancestral mice of the MSKR strain were captured.

Amino Acid Sequence↗