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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 19 recordsLinked to original sources
PubMed2007

Regulation of calprotectin expression by interleukin-1alpha and transforming growth factor-beta in human gingival keratinocytes.

BACKGROUND AND OBJECTIVE: Calprotectin, a heterodimer of S100A8 and S100A9 with antimicrobial properties, is expressed in gingival keratinocytes and plays an important role in innate immunity. Because calprotectin expression is localized in the spinous cell layer of the gingival epithelium, we hypothesized that the expression of calprotectin in keratinocytes is related to the differentiation stage. The aim of the present study was to investigate the relationship between calprotectin expression and keratinocyte differentiation using some factors that regulated its differentiation. MATERIAL AND METHODS: Normal human gingival keratinocytes were isolated from gingival tissues obtained at the extraction of wisdom teeth, and were cultured in serum-free keratinocyte medium supplemented with interleukin-1alpha or calcium, which promote keratinocyte differentiation, and transforming frowth factor-beta (TGF-beta) or retinoic acid, which suppress its differentiation. The expression of S100A8/A9 mRNA and the production of calprotectin in normal human gingival keratinocytes were examined by northern blotting and enzyme-linked immunosorbent assay, respectively. The expression of cytokeratin 14, involucrin and filaggrin (marker proteins of keratinocyte differentiation) was investigated by immunohistochemical staining, and the DNA-binding activity of CCAAT/enhancer binding protein alpha (C/EBPalpha), a transcription factor, was examined by electrophoretic mobility shift assay. RESULTS: The expression of S100A8/A9 mRNA and the production of calprotectin were increased by interleukin-1alpha and calcium, but decreased by TGF-beta. RA inhibited the expression of S100A8/A9 and keratinocyte differentiation, which were induced by interleukin-1alpha. C/EBPalpha DNA-binding activity in normal human gingival keratinocytes was enhanced by interleukin-1alpha and calcium, but suppressed by TGF-beta. CONCLUSION: The present study suggests that calprotectin expression is related to keratinocyte differentiation and that C/EBPalpha is a regulator of calprotectin expression in keratinocytes.

CCAAT-Enhancer-Binding Protein-alpha↗
PubMed2007

Milk basic protein increases alveolar bone formation in rat experimental periodontitis.

BACKGROUND AND OBJECTIVE: It is conceivable that the active components extracted from milk whey protein (i.e. milk basic protein, MBP) stimulate bone formation and suppress bone resorption. Periodontitis is characterized by excessive alveolar bone resorption. We examined whether milk basic protein could recover alveolar bone loss in rat experimental periodontitis. MATERIAL AND METHODS: A nylon ligature was placed around the cervix of molars in 8-wk-old male Fischer rats for 20 d. Then, the ligature was removed and a powder diet containing 0.2 or 1.0% milk basic protein was provided daily for another 45-90 d. On days 45 and 90, the maxillae were extracted and analyzed using microcomputerized tomography (micro-CT), followed by histological analysis. RESULTS: Micro-CT images showed that alveolar bone resorption was severely induced around the molar by the 20-d ligature procedure. Treatment with high-dose milk basic protein (1.0%) clearly recovered ligature-induced alveolar bone resorption on days 45 and 90, whereas low-dose milk basic protein (0.2%) did not show such a clear effect. Histological examination clarified that the osteoid thickness of alveolar bone was dose dependently increased by milk basic protein treatment for 90 d. CONCLUSION: These findings suggest that a systemic administration of milk basic protein may be effective for the recovery of alveolar bone loss in periodontitis.

Alveolar Bone Loss↗
PubMed2006

Cytoplasmic antineutrophil cytoplasmic antibody positive pauci-immune glomerulonephritis associated with infectious endocarditis.

Renal deterioration often occurs in cases of infectious endocarditis (IE), but, IE- associated nephritis with rapidly progressive glomerulonephritis (RPGN) is rare. Patients with severe infection (e.g., IE) sometimes show positivity for cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA). Therefore, diagnosis and treatment are very difficult in cases of RPGN with IE and positivity for C-ANCA. Such cases are rare, only 12 have been reported in the English literature. Herein, we describe the case of a 50-year-old man who presented with RPGN with IE and tested positively for C-ANCA. He was referred to our hospital because of leg edema, purpura and renal dysfunction. Laboratory tests revealed serum creatinine elevation and positivity for C-ANCA and proteinase 3-specific (PR3)-ANCA. RPGN and acute renal failure were diagnosed. Hemodialysis and steroid therapy were started. Streptococcus oralis was isolated by blood culture. Transthoracic echocardiography revealed grade III mitral valve insufficiency with two vegetations. Therefore, IE was diagnosed. The steroid therapy was stopped, and antibiotic therapy was begun. Because there was no improvement, surgical therapy was performed. The operation was successful, but the patient died of brain hemorrhage. Our experience in this case indicates C/PR3-ANCA positive RPGN must be ruled out in patients with infectious disease, particularly IE, together with renal symptoms, and renal biopsy should be performed.

Acute Kidney Injury↗
PubMed2005

Patency assessment of the internal jugular vein after neck dissection.

Twenty-seven patients with oral malignant tumours, who underwent neck dissection with preservation of the internal jugular vein (IJV), were studied retrospectively to evaluate patency of the IJV. Twenty-three patients underwent ablative surgery of the primary lesion with neck dissection and 4 underwent neck dissection alone. Three patients received simple closure and skin grafting of the primary lesion, and 20 received reconstruction surgery (4 platysma flaps, 3 radial forearm flaps, 3 lateral upper arm flaps, 2 pectoralis major myocutaneous flaps and 8 rectus abdominis myocutaneous flaps). The maximum and minimum diameters of the IJV as measured on computed tomographic (CT) scans were used to assess patency. The cross-sectional area of the IJV and the ratio of its long axis to short axis (L/S ratio) were calculated. The relation between the change in IJV status and the type of flap used for reconstruction was also examined. Occlusion of the IJV was present in 3.7% of the patients, and 'narrowing' was present in 63.6%. The size of the flap significantly correlated with 'narrowing' of the IJV, suggesting that 'narrowing' was caused mainly by compression due to the flap.

Carcinoma, Squamous Cell↗
PubMed2005

Application of fuzzy inference to European patients to predict cervical lymph node metastasis in carcinoma of the tongue.

In head and neck cancers, the presence of cervical lymph node metastasis is an important determinant of outcome. Many attempts have been made to predict cervical lymph node metastasis, but the accuracy of currently available techniques remains inadequate. We used fuzzy inference to predict cervical lymph node metastasis retrospectively in 75 patients with squamous cell carcinoma of the tongue and prospectively in 23 patients. Our model was based on three variables: tumor size, keratinization, and mode of invasion. The accuracy of fuzzy inference for the prediction of cervical lymph node metastasis in the 75 patients studied retrospectively was 86.7%, the sensitivity was 70.8%, and the specificity was 94.1%. In the 23 patients studied prospectively, the accuracy was 91.3%, the sensitivity was 50.0%, and the specificity was 95.2%. The accuracy obtained in this European series of patients was similar to that previously obtained in Japanese patients. We conclude that fuzzy inference may be a useful method for predicting cervical lymph node metastasis. Its high specificity is likely to reduce the number of unnecessary neck dissections. However, the current level sensitivity is inadequate for routine clinical use. Therefore, other predictors of lymph node metastasis should be identified to refine the current model.

Carcinoma, Squamous Cell↗
PubMed2005

The linoleic acid derivative FR236924 facilitates hippocampal synaptic transmission by enhancing activity of presynaptic alpha7 acetylcholine receptors on the glutamatergic terminals.

The present study aimed at understanding the effect of FR236924, a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, on hippocampal synaptic transmission in both the in vitro and in vivo systems. FR236924 increased the rate of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated miniature excitatory postsynaptic currents, without affecting the amplitude, triggered by nicotine in CA1 pyramidal neurons of rat hippocampal slices, that is inhibited by GF109203X, a selective protein kinase C (PKC) inhibitor or alpha-bungarotoxin, an inhibitor of alpha7 acetylcholine (ACh) receptors. FR236924 stimulated glutamate release from rat hippocampal slices and in the hippocampus of freely behaving rats, and the effect was also inhibited by GF109203X or alpha-bungarotoxin. FR236924 induced a transient huge potentiation followed by a long-lasting potentiation in the slope of field excitatory postsynaptic potentials recorded from the CA1 region of rat hippocampal slices, and the latter effect was blocked by GF109203X or alpha-bungarotoxin. Likewise, the compound persistently facilitated hippocampal synaptic transmission in the CA1 region of the intact rat hippocampus. It is concluded from these results that FR236924 stimulates glutamate release by functionally targeting presynaptic alpha7 ACh receptors on the glutamatergic terminals under the influence of PKC, responsible for the facilitatory action on hippocampal synaptic transmission. This may provide evidence for a link between cis-unsaturated free fatty acids and presynaptic alpha7 ACh receptors in hippocampal synaptic plasticity.

Alkanes↗
PubMed2005

Reduction of a vascular endothelial growth factor receptor, fetal liver kinase-1, by antisense oligonucleotides induces motor neuron death in rat spinal cord exposed to hypoxia.

Vascular endothelial growth factor (VEGF) is reported to play a neuroprotective role through a VEGF receptor, fetal liver kinase-1 (Flk-1) in vitro. We investigated whether reduction of Flk-1 could induce motor neuron loss in rat spinal cord by inhibiting the expression of Flk-1 in rat spinal cord using antisense oligodeoxynucleotides (ODNs) against the Flk-1 receptor. Rat spinal cord was repetitively exposed to 12% hypoxia, and the change of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and the mitogen-activated protein kinase kinase (MEK)/extracellular-signal-regulated kinase (ERK) pathway was examined. Intrathecal infusion of Flk-1 antisense ODNs for 7 days suppressed almost completely Flk-1 expression in the lumbar segment of the spinal cord and was followed by a hypoxic challenge with 12% oxygen for 1 h that was repeated for 7 more days. In the lumbar segment, we observed that reduced Flk-1 expression and hypoxic challenge for 7 days resulted in approximately 50% loss of motor neurons, in which the activation of Akt and ERK, that is, increased levels of phosphorylated-Akt and of phosphorylated-ERK by hypoxia, was markedly inhibited. In contrast, the reduction of Flk-1 expression alone did not induce motor neuron loss. These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways.

Animals↗
PubMed2005

Alpha 2 integrin +807 polymorphism in drug-induced gingival overgrowth.

Alpha2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the alpha2 integrin gene is associated with high/low alpha2 integrin expression. The aim of this study was to test the hypothesis that expression of alpha2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 - 6.10; P < 0.05). The present findings suggest that the alpha2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.

Adolescent↗
PubMed2005

Two cases of feline malignant craniopharyngioma.

Tumors at the cranial base in 2 cats (a 9 1/2-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multi-angular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.

Animals↗
PubMed2004

A novel melon flexivirus transmitted by whitefly.

In recent years, a viral disease on melon plants has become a serious problem in Brazil. Symptoms were principally yellowing and mottling on older leaves. Long filamentous virus particles, resembling those of carlaviruses, were seen in symptomatic leaves. In this study, the 3' terminal region of the virus genome isolated from an infected plant, including the last two ORFs, was cloned and sequenced. The sequence comprised a polyadenilated tail and two ORFs, one exhibiting similarity to potexvirus and carlavirus coat protein gene and the second to a carlavirus protein with potential nucleic acid-binding property. The sequence analysis, the genome organization and the particle morphology indicated that the virus could be classified as a novel whitefly-transmitted flexivirus. The name Melon yellowing-associated virus (MYaV) is tentatively suggested for this virus.

Amino Acid Sequence↗
PubMed2004

Cytokine and antibody production during the course of resolution in Plasmodium yoelii 17XL-infected BALB/c mice treated with febrifugine and isofebrifugine mixture from leaves of Hydrangea macrophylla var. Otaksa.

Cytokine and antibody production was investigated during the course of resolution of primary infection in Plasmodium yoelii 17XL-infected BALB/c mice treated with a mixture of febrifugine and isofebrifugine. The infected mice in an untreated control group showed a progressively increasing parasitemia, leading to mouse death. In contrast, infected mice given the mixture orally showed low parasitemia levels during administration. Following a transient increase in parasitemia in the bloodstream of the treated mice, no parasites could be detected by microscopic examination. Analysis of cytokines in plasma showed that the plasma IFN-gamma levels elevated significantly within the first week of infection in both groups. Furthermore, on day 20 the plasma IFN-gamma and IL-4 levels elevated significantly in the treated mice and the production of both cytokines was sustained until at least day 40. The production of both cytokines in the treated mice was coincident with a decrease in parasitemia. The production of parasite-specific antibodies in the course of P. yoelii 17XL infection was also monitored. In the drug-treated mice, the titers of parasite-specific IgG1, IgG2a, IgG2b and IgG3 elevated significantly from day 20; and the production of parasite-specific antibodies was coincident with a decrease in parasite numbers in the bloodstream.

Animals↗
PubMed2004

Induction of calprotectin release by Porphyromonas gingivalis lipopolysaccharide in human neutrophils.

Calprotectin, a major cytosolic protein of leukocytes, is detected in neutrophils, monocytes/macrophages, and epithelial cells. This protein is known to be a marker for several inflammatory diseases and is detected in inflammatory gingival tissue with periodontal disease. Recently, we found that the calprotectin level in gingival crevicular fluid from periodontitis patients was significantly higher than that of healthy subjects. However, the regulation of calprotectin in periodontal disease is unclear. In the present study, we investigated the effect of lipopolysaccharides of periodontopathic bacteria on calprotectin release from human neutrophils. Neutrophils from healthy donors were treated with lipopolysaccharides from Porphyromonas gingivalis (P-LPS), Actinobacillus actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, and Escherichia coli. Calprotectin of neutrophil was identified by immunoblotting and calprotectin amount was determined by ELISA. Two subunits (10 and 14 kDa) of calprotectin were observed in the cell and medium fractions from neutrophils. P-LPS increased calprotectin release from seven to 16 times the control level after 30 min and its effect appeared in a dose-dependent manner (10-1000 ng/ml). Lipopolysaccharides from A. actinomycetemcomitans, P. intermedia, F. nucleatum, and E. coli also induced calprotectin release from neutrophils. These results suggest that lipopolysaccharides from periodontopathic bacteria induce calprotectin release from human neutrophils.

Adult↗
PubMed2004

Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy, pulmonary function, and high-resolution computed tomography lung densitometry in elderly patients with asthma.

BACKGROUND: Smoking is the most important cause of chronic obstructive pulmonary disease (COPD). However, the influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study attempted to clarify the influence of cigarette smoking on elderly asthmatics. METHODS: Forty-eight asthmatics over 70 years old (25 ex-smokers and 23 never-smokers) and 20 patients with COPD over 70 years old (all ex-smokers) were studied to determine the influence of cigarette smoking on IgE-mediated allergy (total IgE, IgE antibodies against inhalant allergens, bronchial hyper-responsiveness (BHR), generation of leukotriene (LT) B4 and C4), pulmonary function, and the relative area of lung showing attenuation values less than -950 Hounsfield units (RA950) on high-resolution computed tomography scans. RESULTS: The incidence of positive IgE antibodies against inhalant allergens, BHR, and the generation of leukotriene B4 (LTB4) by leucocytes were significantly increased in patients with a history of smoking compared with those without. Residual volume (%RV) was significantly increased, and diffusing capacity for carbon monoxide was significantly decreased in ex-smokers with asthma and COPD compared with never-smokers with asthma. Inspiratory RA950 and ratio of expiratory RA950 to inspiratory RA950 were significantly larger in asthmatics with a smoking history than in those without, and in COPD patients than in asthmatics. CONCLUSION: Cigarette smoking enhances the production of IgE antibodies, BHR, and generation of LTB4 by leucocytes in elderly asthmatics. Increased hyper-inflation or emphysematous changes of the lungs expressed by increased RA950, closely related to %RV, was more frequently observed in ex-smokers compared with never-smokers.

Aged↗
PubMed2004

Membranous glomerulonephritis associated with hepatitis C virus infection: case report and literature review.

We describe the case of a 51-year-old man with hepatitis C virus (HCV) infection and a 3-month history of facial edema. Laboratory tests upon admission for renal biopsy showed normal renal function and normocomplementemia. Serum HCV antibody (Ab) and cryoglobulin were positive. Renal biopsy specimens showed features of membranous glomerulonephritis. The likely cause was immune complex-mediated glomerulonephritis associated with HCV infection. Reports of similar cases in the literature show the normocomplementemia and negative or slightly positive cryoglobulins observed in our case as well as seropositivity for circulating immune complexes containing HCV RNA. In our case, electron microscopic examination of the subepithelial glomerular lesions revealed massive virus-like particles within unusual multilayers of electron-dense deposits (EDDs), suggesting the existence of HCV in the glomeruli. In the addition to the unique histopathological feature the presence of La/SS-B antibody in his serum indicated an abnormal immune response associated with HCV. We advise him to undergo the therapy with new type of IFN such as pegIFN-alpha2a and/or anti-viral agent like ribavirin to achieve clinical and histopathological improvement.

Glomerulonephritis, Membranous↗
PubMed2003

Suppression of the charge-density-wave state in Sr14Cu24O41 by calcium doping.

The charge response in the spin chain and/or ladder compound Sr14-xCaxCu24O41 is characterized by dc resistivity, low-frequency dielectric spectroscopy and optical spectroscopy. We identify a phase transition below which a charge-density wave (CDW) develops in the ladder arrays. Calcium doping suppresses this phase with the transition temperature decreasing from 210 K for x=0 to 10 K for x=9, and the CDW gap from 130 meV down to 3 meV, respectively. This suppression is due to the worsened nesting originating from the increase of the interladder tight-binding hopping integrals, as well as from disorder introduced at the Sr sites. These results altogether speak in favor of two-dimensional superconductivity under pressure.

Journal Article↗
PubMed2003

Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.

Adult↗
PubMed2003

Mechanisms of cytosolic Ca2+ suppression by prostaglandin E2 receptors in rat melanotrophs.

We have previously reported that voltage-dependent Ca2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E2 (PGE2). In this study, mechanisms involved in the inhibitory actions of PGE2 receptors of rat melanotrophs were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR), Ca2+-imaging and whole-cell, patch-clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP1-4). PGE2 reversibly suppressed the cytosolic Ca2+ concentration ([Ca2+]i). The maximum reduction in [Ca2+]i by PGE2 was comparable to that by dopamine or to that by extracellular Ca2+ removal. RT-PCR analysis of all four EP receptors revealed that EP3 and EP4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE2 to suppress [Ca2+]i were mimicked by the selective EP3 agonist, ONO-AE-248, whereas three other EP agonists, ONO-DI-004 (EP1), ONO-AE1-259 (EP2) and ONO-AE1-329 (EP4), had little or no effect on [Ca2+]i. All four G-protein activated inward rectifying K+ (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT-PCR. Dopamine concentration-dependently activated GIRK currents, whereas PGE2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE2 acts on EP3 receptors to suppress Ca2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE2.

Animals↗