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Biomedical subjects

Tatsuya Okamoto

Publications and source records attributed to Tatsuya Okamoto.

At least 19 recordsLinked to original sources
PubMed2006

Helicobacter cinaedi cellulitis and bacteremia in immunocompetent hosts after orthopedic surgery.

At various times after orthopedic operations (more than a few weeks, with an average of 29.9 days), 11 patients had a sudden onset of high temperature (average 38.9 degrees C) and local cellulitis at different sites on the operated sides. The wounds had completely healed, without complicated infections, when the cellulitis occurred. The clinical picture of cellulitis in all patients was atypical: diffuse salmon-pink skin color, local heat, swelling, spontaneous pain, and tenderness but no eruptions. No patient had any underlying immunocompromising conditions or had been given immunosuppressive agents. Gram-negative spiral bacteria were isolated from blood cultures and were identified as Helicobacter cinaedi on the basis of 16S rRNA gene sequencing and DNA-DNA hybridization using standard strains. By means of phylogenetic analysis, we divided these clinical isolates into two clones. The H. cinaedi strain isolated via fecal cultures from two patients without intestinal symptoms was the same clone as the blood isolate. All isolates were quite susceptible to various antibiotics, and clinical and inflammatory symptoms of bacteremia and cellulitis improved after treatment with penicillins and cephalosporins. A relatively high incidence of recurrence of the same disease was observed, however. Almost all patients responded immunologically to the infection, as evidenced by the production of serum antibody against H. cinaedi. We thus suggest that H. cinaedi should not be regarded as simply an opportunistic pathogen but that it may be a pathogen in immunocompetent hosts and may cause infections together with bacteremia and cellulitis.

Adult↗
PubMed2006

Lithium and dementia: a preliminary study.

Recent studies have shown that lithium may block the accumulation of amyloid-beta (Abeta) peptides and to inhibit the hyperphosphorylation of tau via the inhibition of GSK-3alpha in the brain of mice. The purpose of the present study is to examine whether lithium could potentially be effective for the prevention of Alzheimer's disease. We investigated the clinical records of 1,423 outpatients at a university psychiatric outpatient clinic and classified patients according to the following criteria: (a) absence of a diagnosis of dementia, (b) age 60 years or older, and (c) lithium had been prescribed and/or was currently prescribed. We compared these patients with randomly selected age and gender matched control group who had never been prescribed lithium. Despite no significant difference in MMSE scores between the lithium group, which consisted of patients receiving lithium treatment, and the control group, those who had previously received lithium and/or were currently prescribed lithium had significantly better MMSE scores than the control patients. The findings provide partial evidence to support the contention that lithium could offer hope as a preventive treatment for Alzheimer's disease. Further prospective studies with a large number of patients are warranted to investigate this potentially important effect.

Aged↗
PubMed2006

Guanine nitration in idiopathic pulmonary fibrosis and its implication for carcinogenesis.

RATIONALE: Nitric oxide (NO)-induced nitrative stress of nucleic acids, as evidenced by guanine nitration, appears to be involved in inflammation-induced carcinogenesis. A high incidence of lung cancer in idiopathic pulmonary fibrosis (IPF) is the major reason for poor prognosis in patients with IPF. OBJECTIVES AND METHODS: We immunohistochemically analyzed the formation and localization of 8-nitroguanine in lung tissues from control subjects, patients with IPF, and patients with lung cancer. MAIN RESULTS: Immunohistochemical analysis of control smoker and nonsmoker lungs showed weak immunoreactivity for 8-nitroguanine, mainly in cytoplasm of bronchial epithelial cells. In addition to the bronchial epithelial cells, metaplastic regenerated epithelial cells overlying dense fibrotic lesions in IPF showed strong 8-nitroguanine staining in the cytoplasm. The staining in these metaplastic cells colocalized with staining of inducible and endothelial NO synthases and 8-oxodeoxyguanosine, as evidenced by double-immunostaining analysis. Confocal and immunoelectron microscopy revealed localization of 8-nitroguanine in metaplastic epithelial cytoplasm, mostly in mitochondria. Appreciable 8-nitroguanine immunostaining was also observed in both nuclei and cytoplasm of malignant epithelial cells in squamous cell carcinoma. No significant difference was found in the epithelial 8-nitroguanine formation between control smokers and nonsmokers, but much higher guanine nitration was observed in patients with IPF than in control subjects and patients with lung cancer, via a quantitative immunofluorescence image analysis. CONCLUSIONS: The present study indicates that not only oxidative stress but also nitrative stress induced by NO may participate in the pathogenesis of epithelial cell damage and aberrant regeneration occurring in IPF. Thus, guanine nitration may be a major risk factor for lung cancer development in IPF.

Adult↗
PubMed2006

Receiver-operating characteristic analysis of leukocyte counts and serum C-reactive protein levels in children with advanced appendicitis.

PURPOSE: To assess the diagnostic value of the white blood cell count (WBC) and serum C-reactive protein (CRP) level in children with advanced appendicitis. METHODS: We reviewed 289 children ranging in age from 3 to 15 years old, who underwent appendectomy in our hospital between 1993 and 2003. The advanced appendicitis group consisted of patients with associated perforation, abscess formation, or purulent ascites, and the simple appendicitis group consisted of patients who underwent uncomplicated appendectomy. We compared the age, sex, duration of abdominal pain before surgery, preoperative WBC and CRP level, and hospital stay in the two groups. We analyzed the diagnostic value of WBC and CRP level using a receiver-operating characteristic (ROC) curve. RESULTS: The children in the advanced appendicitis group had a significantly longer duration of pain, a higher serum CRP level, and longer hospitalization than those in the simple group. The serum CRP levels had good diagnostic value in differentiating between the advanced and simple groups. Both the CRP level and the WBC in the patients who suffered abdominal pain for longer than 48 h before surgery had diagnostic value in differentiating between the advanced and simple groups. CONCLUSION: These findings suggest that increased values of CRP and WBC more than 48 h after the onset of acute abdominal symptoms are indicators of advanced appendicitis.

Abscess↗
PubMed2006

[Clinical analysis of the acute exacerbation in patients with idiopathic pulmonary fibrosis].

The clinical course of idiopathic pulmonary fibrosis (IPF) is chronic, but some patients with IPF have phases of accelerated deterioration superimposed on the chronic course of their illness, which is referred to as acute exacerbation (Aex) of IPF. To evaluate the clinical feature of Aex of IPF, we analyzed clinical findings of the 112 patients with IPF admitted to our hospital from 1994 to 2004. Of the 112 patients 56 with IPF died during the observation period due to Aex (42.9%), lung cancer (21.4%), chronic respiratory failure (14.3%), and lower respiratory infections (8.9%). Aex of IPF was seen 28 of 112 patients with IPF (25.0%) and 24 patients (85.7%) died with Aex. The median survival time (MST) after the onset of Aex was 0.9 months. The 5-yr survival rate of all patients with IPF was 38.3% and the MST was 3.1 yrs after diagnosis. On the other hand, the 5-yr survival rate and MST was 10.7% and 0.6 yrs in patients with Aex of IPF. We treated the patients with Aex with methylprednisolone pulse therapy in combination with cyclophosphamide or cyclosporine A, which did not significantly improve the outcome of Aex. In conclusion, there is little evidence that currently accepted treatments are effective in Aex of IPF, and further studies are needed to clarify the pathogenesis and contribute to the prevention of Aex.

Aged↗
PubMed2006

[Successful treatment by voliconazole for pulmonary and adductor magnus muscle aspergillosis induced by immunosuppressive therapy for hypersensitivity pneumonia].

A 74-year-old woman was treated with steroid and cyclosporine A for hypersensitivity pneumonia. To examine the causes of general fatigue and increased levels of beta-D glucan in serum, she was admitted to our hospital. Chest computed tomography (CT) scan revealed nodular opacity with a well-defined margin in the right S1. 67Ga scintigraphy image showed high uptake in the left thigh and CT showed circularly enhanced lesions in the thigh. An ultrasonography-guided needle aspiration and biopsy of the muscle abscess allowed isolation of Aspergillus fumigatus and evidence of necrotic tissues around the granuloma formation. We therefore diagnosed invasive aspergillosis. Because of the poor response to initial therapy with micafungin and itraconazole for 4 weeks, we treated her with voliconazole (VCZ). Spectacular regression of lung lesions and muscle abscesses was rapidly achieved. Furthermore, the high level of beta-D glucan in serum decreased gradually. This case suggests that administration of VCZ can be recommended for deep seated mycoses.

Aged↗
PubMed2005

Nitrative stress through formation of 8-nitroguanosine: insights into microbial pathogenesis.

Reactive oxygen and nitrogen species, respectively, mediate oxidative and nitrative stresses by means of oxidation and nitration of various biomolecules including proteins, lipids, and nucleic acids. We have observed nitric oxide (NO)-dependent formation of 8-nitroguanosine and 3-nitrotyrosine during microbial infection, and we determined that both 8-nitroguanosine and 3-nitrotyrosine are useful biomarkers of nitrative stress. Of importance, however, is the great difference in biological characteristics of these two nitrated compounds. 8-Nitroguanosine has unique biochemical and pharmacological properties such as redox activity and mutagenic potential, which 3-nitrotyrosine does not. In this review, we discuss the mechanism of nitrative stress occurring during microbial infections, with special emphasis on biological functions of 8-nitroguanosine formed via NO during the host response to pathogens. These findings provide insights into NO-mediated pathogenesis not only of viral infections but also of many other diseases.

Animals↗
PubMed2005

Molecular mechanism for connective tissue destruction by dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis.

Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis.

Animals↗
PubMed2004

Predicting denial function of schizophrenic patients by the picture completion subtest of WAIS-R.

In the previous study, picture completion (PC) test scores of Wechsler Adult Intelligence Scale Revised (WAIS-R) were negatively associated with recognition of mental illness measured by Schedule for the Assessment of Insight (SAI). Therefore, it can be hypothesized that function measured by the PC test is positively associated with denial function. To investigate this hypothesis, we investigated the relationship between two picture tests (picture completion and picture arrangement) of the WAIS-R and denial function tests (lie scale, frequency scale and correction scale) of the Minnesota Multiphasic Personality Inventory (MMPI) in 26 schizophrenic patients. As a result, the lie scale score and the correction scale score were positively and significantly associated with picture completion whereas no scale score was significantly associated with picture arrangement. The present findings suggest that the positive association between function measured by the PC test and denial function measured by lie and correction scale scores. Further studies are warranted to investigate the usefulness of the PC test for the measurement of denial function in schizophrenia.

Adult↗
PubMed2004

Molecular mechanism for activation and regulation of matrix metalloproteinases during bacterial infections and respiratory inflammation.

Matrix metalloproteinases (MMPs) are critical mediators of tissue remodeling. Inappropriate regulation of MMPs causes many pathological events, including microbial invasion and inflammatory tissue damage. Some of the bacterial exoproteinases can effectively activate pro-MMPs (inactive zymogens) via limited proteolysis around their autoinhibitory domains. In addition, overproduction of nitric oxide (NO) may contribute to respiratory inflammation via the formation of reactive nitrogen species (RNS). Several studies have identified regulatory properties of NO/RNS on biomolecules due to functional modification of their cysteine residues. In fact, NO/RNS can mediate activation and expression of MMPs, because RNS can interact with a cysteine switch in the autoinhibitory domain, thus converting proMMPs into their active forms without proteolysis. Many studies have indicated that NO/RNS can participate in expression of various genes that affect immune-inflammatory responses, including MMPs. Although NO in some cases upregulates MMPs, S -nitrosothiols downregulate MMP-9 expression by suppressing the NF-kappaB pathway. While microbial proteinases cause excessive activation of MMPs and contribute to microbial pathogenesis, NO/RNS may modulate expression and activation of MMPs as well as various inflammatory mediators, depending on the redox status at sites of inflammation. Therefore, appropriate regulation of MMPs may be of potential therapeutic value for various infections and inflammatory lung diseases.

Animals↗
PubMed2003

Multiple contributing roles for NOS2 in LPS-induced acute airway inflammation in mice.

Acute lung inflammation and injury were induced by intranasal instillation of lipopolysaccharide (LPS) in normal and type 2 nitric oxide synthase (NOS2)-deficient (NOS2-/-) C57BL/6 mice. LPS-induced increases in extravasated airway neutrophils and in lung lavage fluid of TNF-alpha and macrophage inflammatory protein-2 were markedly lower in NOS2-/- than in wild-type mice, indicating that NOS2-derived nitric oxide (NO.) participates in inflammatory cytokine production and neutrophil recruitment. Instillation of LPS also increased total lung lavage protein and induced matrix metalloproteinase-9 and mucin 5AC, as indexes of lung epithelial injury and/or mucus hyperplasia, and increased tyrosine nitration of lung lavage proteins, a marker of oxidative injury. All these responses were less pronounced in NOS2-/- than in wild-type mice. Inhibition of NOS activity also suppressed production of TNF-alpha and macrophage inflammatory protein-2 by LPS-stimulated mouse alveolar MH-S macrophages, and this was restored by NO. donors, illustrating involvement of NO. in macrophage cytokine signaling. Oligonucleotide microarray (GeneChip) analysis of global lung gene expression revealed that LPS inhalation induced a range of transcripts encoding proinflammatory cytokines and chemokines, stress-inducible factors, and other extracellular factors and suppressed mRNAs encoding certain cytoskeletal proteins and signaling proteins, responses that were generally attenuated in NOS2-/- mice. Comparison of both mouse strains revealed altered expression of several cytoskeletal proteins, cell surface proteins, and signaling proteins in NOS2-/- mice, changes that may partly explain the reduced responsiveness to LPS. Collectively, our results suggest that NOS2 participates in the acute inflammatory response to LPS by multiple mechanisms: involvement in proinflammatory cytokine signaling and alteration of the expression of various genes that affect inflammatory-immune responses to LPS.

Acute Disease↗
PubMed2003

Induction of stress proteins and MMP-9 by 0.8 ppm of ozone in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant pollutants to which cutaneous tissues are exposed. O(3) exposure has been shown to induce antioxidant depletion as well as the oxidation of lipids and proteins within the outermost skin layer, the stratum corneum. However, relatively little is known regarding the potential effects of O(3) on the cellular constituents of the underlying skin epidermis and dermis. In the present study, hairless mice exposed for 6 h to 0.8 ppm O(3) showed increases in lipid peroxidation, as quantitated by increases in 4-hydroxynonenal-protein adducts. O(3) exposure caused an induction of the stress proteins HSP27 and heme oxygenase-1 (HO-1), starting at 6 h and increasing up to 18 h after O(3) exposure. This was accompanied by an increase in matrix metalloproteinase-9 (MMP-9) mRNA and activity levels, indicative of possible injurious-reparative processes. Collectively, our data demonstrate that skin exposure to O(3) not only affects antioxidant levels and oxidation markers in the outermost stratum corneum layer, but also induces cellular stress responses in the deeper cellular layers of the skin.

Animals↗
PubMed2002

Ozone exposure activates oxidative stress responses in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant to which skin is exposed. O(3) exposure has previously been shown to induce antioxidant depletion as well as lipid and protein oxidation in the outermost skin layer, the stratum corneum (SC), but little is known regarding the potential effects of O(3) on the skin epidermis and dermis. To evaluate such skin responses to O(3), SKH-1 hairless mice were exposed for 2 h to 8.0 ppm O(3) or to ambient air. O(3) exposure caused a significant increase in skin carbonyls (28%) compared to the skin of air exposed control animals. An evident increase in 4-hydroxynonenal-protein adducts was detected after O(3) exposure. O(3) exposure caused a rapid up-regulation of HSP27 (20-fold), and more delayed induction of HSP70 (2.8-fold) and heme oxygenase-1 (5-fold). O(3) exposure also led to the induction of nitric oxide synthase (iNOS) 6-12 h following O(3) exposure. We conclude that skin exposure to high levels of O(3) not only affects antioxidant levels and oxidation markers in the SC, but also induces stress responses in the active layers of the skin, most likely by indirect mechanisms, since it is unlikely that O(3) itself penetrates the protective SC layers.

Aldehydes↗