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1.
Appl Opt ; 62(29): 7549-7559, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37855461

ABSTRACT

Although a lateral-shear interferometer is robust against optical component vibrations, its interferogram provides information about differential wavefronts rather than the wavefronts themselves, resulting in the loss of specific frequency components. Previous studies have addressed this limitation by measuring four interferograms with different shear amounts to accurately restore the two-dimensional wavefront. This study proposes a technique that employs spectral interpolation to reduce the number of required interferograms. The proposed approach introduces an origin-shift technique for accurate spectral interpolation, which in turn is implemented by combining two methods: natural extension and least-squares determination of ambiguities in uniform biases. Numerical simulations confirmed that the proposed method accurately restored a two-dimensional wavefront from just two interferograms, thereby indicating its potential to address the limitations of the lateral-shear interferometer.

2.
Respir Investig ; 61(6): 760-767, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37716284

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Its symptoms range from mild to severe, with the latter often being life-threatening. This study aims to assess the effects of low-dose dexamethasone (DEX) in mild-to-severe COVID-19 pneumonia and examine the final clinical outcomes to identify the optimal therapeutic dose. METHODS: Clinical data from 132 patients hospitalized for COVID-19 pneumonia between January and October 2021 at Yamato Municipal Hospital were retrospectively analyzed. Based on the ratio of peripheral arterial oxygen saturation (SpO2) to inspired fraction of oxygen (FiO2), patients were categorized into the mild (>450, n = 65), moderate (315-450, n = 55), and severe (<315, n = 12) pneumonia groups. The event of interest was defined as the worsening of the patient's condition during treatment (need to increase FiO2 > 0.1). Patients were treated with low-dose DEX (6.6 mg/day) for 10 days. RESULTS: The event-free survival rate decreased significantly in patients with severe pneumonia compared with in those with mild and moderate pneumonia (Bonferroni-adjusted p < 0.02). A total of 16 patients were treated with high-dose corticosteroids because of severe hypoxia. Recovery was observed in all discharged patients with respiratory condition improvement. Low SpO2/FiO2 at admission was significantly associated with serum C-reactive protein levels. CONCLUSIONS: For Japanese patients with COVID-19, severe pneumonia, and SpO2/FiO2 of <315, it may be necessary to administer a dose of corticosteroids of >6.6 mg DEX.


Subject(s)
COVID-19 , Humans , Retrospective Studies , COVID-19 Drug Treatment , Adrenal Cortex Hormones , Dexamethasone
3.
PLoS One ; 18(9): e0291489, 2023.
Article in English | MEDLINE | ID: mdl-37725604

ABSTRACT

BACKGROUND: Among patients with idiopathic pulmonary fibrosis (IPF), few studies have investigated the clinical impact of anti-fibrotic treatment (AFT) with and without comorbidities. The aim of the study was to determine whether Charlson Comorbidity Index score (CCIS) can predict the efficacy of AFT in patients with IPF. METHODS: We retrospectively assessed data extracted from the medical records of IPF patients who received anti-fibrotic agents between 2009 and 2019. The collected data included age, sex, CCIS, pulmonary function test, high-resolution computed tomography (HRCT) pattern, gender/age/physiology (GAP) score, and 3-year IPF-related events defined as the first acute exacerbation or death within 3 years after starting AFT. RESULTS: We assessed 130 patients (median age, 74 years) who received nintedanib (n = 70) or pirfenidone (n = 60). Median duration of AFT was 425 days. Patients were categorized into high (≥ 3 points) and low (≤ 2 points) CCIS groups. There was no significant difference between the groups in terms of age, sex, duration of AFT, GAP score, or incidence of usual interstitial pneumonia pattern on HRCT except percentage predicted diffusion capacity of lung for carbon monoxide. Also, significant difference was not seen between the groups for 3-year IPF-related events (P = 0.75). Especially, in the low CCIS group but not the high CCIS group, the longer duration of AFT had better disease outcome. CONCLUSION: In the present study, we could not show any relation between CCIS and IPF disease outcomes in patients undergoing AFT, though the longer duration of AFT might be beneficial for IPF outcomes among patients with low CCIS.


Subject(s)
Idiopathic Pulmonary Fibrosis , Aged , Humans , Antifibrotic Agents , Comorbidity , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/epidemiology , Retrospective Studies
4.
Tokai J Exp Clin Med ; 46(3): 142-150, 2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34498251

ABSTRACT

OBJECTIVE: This study aimed to clarify the risks, as perceived by ward nurses, associated with the quality of lighting nurses use during nighttime rounds, and to identify the torch functions nurses need to optimally perform such rounds. METHODS: A semi-structured interview survey was conducted among nurses working in a university hospital. Data were collected regarding nurses' usage of torches during nighttime rounds and whether the color cast by the torches impacts their work efficiency and the risk of medical incidents. Narrative data obtained during the interviews were analyzed using Belerson's method of content analysis. RESULTS: Sixteen nurses participated in this study. Thereupon, 25 categories and 83 subcategories were identified regarding the impact of torchlight on nursing during nighttime rounds, and 10 categories and 38 subcategories were identified regarding the torch functions needed to optimally perform nighttime rounds. The needs included , , , and . CONCLUSIONS: To reduce the risk of medical incidents during nighttime nursing rounds, the use of white-light torches with sufficient brightness and high color rendering is recommended.


Subject(s)
Nurses , Nursing Staff, Hospital , Hospitals , Humans , Qualitative Research
5.
Tokai J Exp Clin Med ; 46(3): 151-161, 2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34498252

ABSTRACT

Cardiovascular disease is a global health problem. According to the World Health Organization, ischemic heart disease was the leading cause of death globally in 2019, followed by stroke. The French paradox, which has been known since the early 1990s, describes the lower incidence of ischemic heart disease in French people despite the consumption of a diet rich in saturated fatty acids. This phenomenon has been attributed to the high intake of red wine, which is rich in polyphenols, namely, resveratrol and piceatannol. It is becoming clear that scirpusin B, a dimer of piceatannol, has anti-atherosclerotic properties such as vasodilation, antioxidant effects, and suppression of postprandial hyperglycemia; nonetheless, the effects of scirpusin B on the cardiovascular system have not been fully elucidated. This review aimed to describe the cardiovascular effects of piceatannol and scirpusin B on aortic and coronary artery dilation and cardiac function and to outline the cardiovascular effects of prostacyclin and nitric oxide, as these substances are involved in the vasodilatory effects exerted by these polyphenols.


Subject(s)
Cardiovascular System , Passiflora , Benzofurans , Fruit , Humans , Polyphenols/pharmacology , Seeds , Stilbenes
6.
Medicina (Kaunas) ; 55(9)2019 Sep 15.
Article in English | MEDLINE | ID: mdl-31540183

ABSTRACT

Background and objectives: Aroma therapy is a complementary therapy using essential oils diluted with carrier oils. Jojoba oils have been widely used as carrier oils. However, limited information is available regarding their effects on blood biochemical parameters. This study aimed to investigate the effect of transdermal administration of jojoba oil on blood biochemical parameters in mice. Materials and Methods: Eight-week-old male hairless mice were randomly divided into naïve control and treatment groups. In the treatment group, mice were topically administered 4 µL of jojoba oil, per gram of body weight, on the dorsa 30 min before euthanasia. Thereafter, serum biochemical parameters were assayed, and gene expression was analyzed in various tissues via a real-time polymerase chain reaction. Results: Serum non-esterified fatty acid (NEFA) levels increased significantly 30 min after topical application of jojoba oil (p < 0.05). Atgl was significantly upregulated in the liver (p < 0.05), and Atgl upregulation in the liver was positively correlated with serum NEFA levels (r = 0.592, p < 0.05). Furthermore, a trend of decreasing fatty acid trafficking-related gene (FABPpm, FATP-1, FATP-3, and FATP-4) expression in the skin after topical application of jojoba oil (p = 0.067, 0.074, 0.076, and 0.082, respectively) was observed. Conclusions: Serum NEFA levels were elevated 30 min after transdermal administration of jojoba oil. The mechanisms of elevated serum NEFA levels might be related to both enhanced lipolysis in the liver and reduced fatty acid trafficking in the skin.


Subject(s)
Lipid Metabolism/drug effects , Plant Oils/administration & dosage , Waxes/pharmacology , Administration, Cutaneous , Animals , Animals, Newborn , Male , Mice , Mice, Hairless , Models, Animal , Phytotherapy , Plant Oils/pharmacology , Random Allocation
7.
J Nat Med ; 71(1): 59-67, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27592007

ABSTRACT

Obesity results from excessive energy intake and physical inactivity, and predisposes one to various diseases. One of these reasons is that enlargement of adipocytes raises the lipid metabolic abnormalities that affect various organs. The skin is one such organ, and it has been reported that subcutaneous adipocyte cells secrete various factors and these factors are involved in reduction of dermal collagen fibers and fragility of the skin in obesity. The present study explored the efficacy of Kaempferia parviflora (KP) in preventing obesity-induced dermatopathy. We used Tsumura Suzuki obese diabetes (TSOD) mice as an obesity model. TSOD mice were fed a standard diet (MF) mixed with either an ethanol extract from KP (KPE), polymethoxyflavonoid-rich extract from KP (PMF), or polymethoxyflavonoid-poor extract from KP (X). We then evaluated the effect of these three KP fractions on aging-like skin damage induced by UVB irradiation. KPE and PMF caused a significant decrease of mouse body weight, and suppressed the increase in the thickness of the subcutaneous fat layer. In addition, KPE shifted the frequency of subcutaneous adipocyte sizes towards smaller cells possibly via its polypharmacological actions. Scanning electron microscopy revealed that the stereostructure of the collagenous fibers in the dermis was better retained in the KPE and PMF groups, in that order. These results offer the first evidence that KPE can attenuate obesity-induced dermatopathy more effectively than PMF, suggesting that KPE (or KP) might be a candidate supplement for preventing obesity-related skin disorders.


Subject(s)
Obesity/complications , Plant Extracts/pharmacology , Real-Time Polymerase Chain Reaction/methods , Skin Diseases, Metabolic/drug therapy , Zingiberaceae/chemistry , Animals , Disease Models, Animal , Male , Mice , Mice, Obese , Skin Diseases, Metabolic/etiology
8.
J Forensic Leg Med ; 19(6): 358-62, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22847057

ABSTRACT

Lime sulfide poisoning by the oral route is rarely encountered in the practice of forensic science, whereas hydrogen sulfide poisoning is seen frequently. We report here two cases of fatal lime sulfide poisoning with several related cases and in addition induced histological damage with acute inflammation in animal models under at similar concentrations. We also evaluated sulfide and thiosulfate concentrations and speculated as to the cause of pancreatic damage in these cases.


Subject(s)
Calcium Compounds/poisoning , Calcium Compounds/toxicity , Pancreas/pathology , Pancreatitis/chemically induced , Sulfides/poisoning , Sulfides/toxicity , Thiosulfates/poisoning , Thiosulfates/toxicity , Adult , Aged , Air Pollutants/poisoning , Air Pollutants/toxicity , Amylases/blood , Animals , Esophagus/pathology , Female , Forensic Pathology , Forensic Toxicology , Humans , Hydrogen Sulfide/poisoning , Hydrogen Sulfide/toxicity , Inflammation/pathology , Liver/pathology , Lung/pathology , Male , Mice , Middle Aged , Necrosis/pathology , Neutrophils/pathology , Pancreatitis/pathology , Respiratory Mucosa/pathology , Stomach/pathology , Suicide , Sulfides/blood , Sulfides/urine , Thiosulfates/blood , Thiosulfates/urine
9.
PLoS One ; 7(6): e39374, 2012.
Article in English | MEDLINE | ID: mdl-22761774

ABSTRACT

Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities.


Subject(s)
Aorta/drug effects , Cholesterol, Dietary/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Tetrazoles/pharmacology , Triglycerides/metabolism , Animals , Aorta/metabolism , Cilostazol , Male , Rabbits , Triglycerides/blood
11.
J Cereb Blood Flow Metab ; 30(2): 343-51, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19809463

ABSTRACT

The aim of this study was to evaluate and compare the effects of anti-platelet agents with different modes of action (cilostazol, aspirin, and clopidogrel) on brain infarction produced by photothrombotic middle-cerebral-artery (MCA) occlusion in male, spontaneously hypertensive rats. Cerebral blood flow (CBF) was measured with laser-Doppler flowmetry in the penumbral cortex. Infarct size was evaluated 24 h after MCA occlusion. The effects of these drugs on infarct size were examined by pretreatment of rats undergoing MCA occlusion. Pretreatment with cilostazol (100 mg/kg) significantly reduced infarct size. In contrast, aspirin (10 mg/kg) and clopidogrel (3 mg/kg) failed to mitigate infarct size, regardless of their apparent inhibitory effects on platelet aggregation. Post-treatment with cilostazol also significantly attenuated the infarct size, associated with improved CBF in the penumbral region. In support of this effect, cilostazol increased nitric oxide (NO) production and prostaglandin-I(2) (PGI(2)) release in cultured human brain microvascular endothelial cells. Cilostazol-induced NO production and PGI(2) release were completely abolished by an NO synthase inhibitor and aspirin, respectively. These findings show that cilostazol reduced brain infarct size due to an improvement in penumbral CBF possibly in association with increased endothelial NO and PGI(2) production.


Subject(s)
Brain Ischemia/drug therapy , Hypertension/drug therapy , Phosphodiesterase Inhibitors/pharmacology , Tetrazoles/pharmacology , Animals , Aspirin/pharmacology , Brain Ischemia/etiology , Brain Ischemia/pathology , Cells, Cultured , Cerebrovascular Circulation/drug effects , Cilostazol , Clopidogrel , Endothelial Cells/drug effects , Epoprostenol/biosynthesis , Humans , Hypertension/complications , Laser-Doppler Flowmetry , Male , Nitric Oxide/biosynthesis , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Rats , Rats, Inbred SHR , Ticlopidine/analogs & derivatives , Ticlopidine/pharmacology
12.
Acta Biomater ; 5(8): 2974-82, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19442768

ABSTRACT

The lipophilic antioxidant vitamin E was used as a surface modifier (or coating agent) of hollow-fiber hemodialyzer membranes with the aim of increasing their biocompatibility and preventing oxidative stress, which are the main clinical drawbacks in hemodialysis (HD) therapy. At present, the redox chemistry of vitamin E-modified dialyzers is not well characterized and there is no standard method to assess the antioxidant capacity of these biomembranes under conditions that simulate those observed during HD therapy. With this study, we developed an original online method to determine the antioxidant capacity of vitamin E-modified dialyzer membranes during circulation experiments. This method is based on a spectrophotometric assay known as the ferric reducing/antioxidant power assay (FRAP). The principle of FRAP and its application to the qualitative and quantitative assessment of miniaturized polysulfone (PS)-based vitamin E-modified dialyzers (PS-VE) were verified by the accurate in vitro analysis of the iron-catalyzed oxidation of vitamin E. The antioxidant capacity of miniaturized PS-VE samples assessed in this study was of 14.5 microM Fe(2+), which corresponded to the transformation of nearly one-third of the vitamin E bound to the hollow-fiber membrane to its oxidation end product alpha-tocopherol quinone. This method shows good reproducibility and intra- and inter-assay precision, and can be easily adapted to determine the redox activity of every type of vitamin E-modified dialyzers during technological investigation, manufacturing control and clinical research.


Subject(s)
Antioxidants/chemistry , Biocompatible Materials/chemistry , Hemodialysis Solutions/chemistry , Membranes, Artificial , Polymers/chemistry , Renal Dialysis/methods , Sulfones/chemistry , Vitamin E/chemistry , Adsorption , Materials Testing , Reactive Oxygen Species/chemistry
13.
Nihon Kokyuki Gakkai Zasshi ; 46(10): 788-92, 2008 Oct.
Article in Japanese | MEDLINE | ID: mdl-19044027

ABSTRACT

We analyzed clinical and microbiological features of six cases involving Mycobacterium fortuitum isolated from sputum or surgical lung specimen. Patients were five men and one woman with an average age of 59. Four cases had a history of pulmonary tuberculosis and three had nontuberculous mycobacterial lung disease. Three out of six cases had underlying chronic obstructive pulmonary disease. Diabetes mellitus was complicated in five cases. All diseases were in the upper lobes of either lung. Clinical symptoms were mainly cough and sputum, while two cases developed pneumothorax. Although all strains showed low sensitivity to standard anti-tuberculous agents, chemotherapy including those drugs or fluoroquinolones and macrolides were successful in all treated cases.


Subject(s)
Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium fortuitum/isolation & purification , Tuberculosis, Pulmonary/microbiology , Adult , Aged , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Drug Resistance, Bacterial , Female , Humans , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium fortuitum/drug effects , Retrospective Studies , Treatment Outcome , Tuberculosis, Pulmonary/drug therapy
14.
Nihon Kokyuki Gakkai Zasshi ; 46(11): 864-9, 2008 Nov.
Article in Japanese | MEDLINE | ID: mdl-19068757

ABSTRACT

We analyzed clinical features of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with underlying chronic respiratory disease, and evaluated the efficacy and tolerability of voriconazole against CNPA in those patients. Voriconazole therapy was indicated in 45 CNPA patients between October 2005 and September 2007, in 23 patients as first-line treatment and in 22 after lack of response to or intolerance of prior antifungal agent. The most common underlying respiratory disease was sequelae of tuberculosis (n = 23) followed by COPD (n = 13). Cavitary lesions were found in 32 patients. Galactomannan antigen test was positive in 29 patients while 28 patients out of 36 were positive for anti-Aspergillus serum antibody. The antibody-negative group had significantly higher levels of galactomannan antigen than the antibody-positive group. Mycological culture or hyphae were positive in 15 patients. Beta-D glucan level was within the normal limit in 27 patients. Clinical, radiological improvement, or both was obtained in 30 patients after an average voriconazole treatment of 4.8 months, with the main adverse effects being visual disturbance and hepatotoxicity. During the observation period 14 patients died due to CNPA or other causes. Although voriconazole demonstrated good efficacy against CNPA, the outcome is still unsatisfactory.


Subject(s)
Aspergillosis/drug therapy , Lung Diseases, Fungal/drug therapy , Pyrimidines/therapeutic use , Respiratory Tract Diseases/complications , Triazoles/therapeutic use , Adult , Aged , Aged, 80 and over , Aspergillosis/complications , Chronic Disease , Female , Humans , Lung Diseases, Fungal/complications , Male , Middle Aged , Treatment Outcome , Voriconazole
15.
Nihon Kokyuki Gakkai Zasshi ; 46(11): 880-8, 2008 Nov.
Article in Japanese | MEDLINE | ID: mdl-19068760

ABSTRACT

We report 4 cases of pulmonary infection due to Mycobacterium szulgai with review of 23 cases previously reported in Japan. All 4 patients were male and two of them in their 20's were found to have abnormal chest X-ray findings recognized on a health checkup without any symptoms. One case had no previous history of illness and had never smoked. Radiographic study showed thick-walled cavities in 3 cases and multiple small nodules in 2, indicating the difficulty of distinguishing M. szulgai infection from pulmonary tuberculosis or M. kansasii infection. Three cases were treated as pulmonary tuberculosis at first, and later we changed the medication referring to the drug susceptibility. In most cases, rifampicin, ethionamide and ethanbutol were used and the medication regimen was successfully completed in all cases. Considering that the detected M. szulgai could be regarded as pathogen in almost all cases, it is important to evaluate the risk factor of patients and not to delay diagnosis and treatment with adhering to usual diagnostic criteria.


Subject(s)
Nontuberculous Mycobacteria , Adult , Aged , Humans , Male , Middle Aged , Mycobacterium Infections, Nontuberculous , Nontuberculous Mycobacteria/pathogenicity , Young Adult
16.
Nihon Kokyuki Gakkai Zasshi ; 46(7): 552-7, 2008 Jul.
Article in Japanese | MEDLINE | ID: mdl-18700574

ABSTRACT

A 71-year-old man presented with a thin-walled cavity in his left lung in November 2006. A previous chest CT in 2003 showed a small thin-walled cavity in his left lingula. Although no obvious change was observed in 2004, the cavity increased its size from 11mm to 14mm in diameter and the wall became thicker in June 2006. On the first visit to our hospital in November 2006, the diameter of the cavity was 30mm and some part of the wall was thinner than on the previous CT. The patient developed pneumothorax one month later and underwent segmentectomy of the left lingula after unsuccessful thoracic drainage. Poorly differentiated adenocarcinoma was identified in both the pleura and the inner wall around the cavity. Lung adenocarcinoma with gradual enlargement of a thin-walled cavity causing pneumothorax has never been reported before. We report here the natural course of lung adenocarcinoma with a thin-walled cavity.


Subject(s)
Adenocarcinoma/complications , Lung Neoplasms/complications , Pneumothorax/etiology , Adenocarcinoma/diagnostic imaging , Aged , Humans , Lung Neoplasms/diagnostic imaging , Male , Pneumothorax/diagnostic imaging , Tomography, X-Ray Computed
17.
Kansenshogaku Zasshi ; 82(2): 73-6, 2008 Mar.
Article in Japanese | MEDLINE | ID: mdl-18411763

ABSTRACT

A 39-year-old man with dyspnea was revealed to have severe pneumothorax and received partial resection of the left upper lobe after unsuccessful drainage. Necrotizing epitheloid granuloma was found in the resected lung and Mycobacterium fortuitum was detected from the lesion. Chemotherapy with levofloxacin and clarithromycin was started one year after surgery because of the newly found nodular shadow near the lesion. The case experienced pyothorax due to pulmonary tuberculosis three years before and Mycobacterium avium pleuritis one year before this episode. Three-time mycobacterial pleural infection in three years seems to be uncommon. Furthermore this is the first report of pneumothorax associated with pulmonary Mycobacterium fortuitum infection.


Subject(s)
Mycobacterium Infections, Nontuberculous/complications , Mycobacterium fortuitum , Pneumothorax/etiology , Tuberculosis, Pulmonary/complications , Adult , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Combined Modality Therapy , Drainage , Drug Resistance, Bacterial , Humans , Levofloxacin , Male , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/therapy , Mycobacterium fortuitum/drug effects , Mycobacterium fortuitum/isolation & purification , Ofloxacin/pharmacology , Ofloxacin/therapeutic use , Pneumonectomy , Pneumothorax/therapy , Recurrence , Treatment Outcome , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/therapy
18.
Environ Sci Technol ; 41(10): 3775-80, 2007 May 15.
Article in English | MEDLINE | ID: mdl-17547212

ABSTRACT

Urban particulate air pollution is associated with an increased incidence of cancers, and especially lung cancer. Organic extracts of airborne particulate matter (APM) cause cancer in mice, and PAHs adsorbed to APM are associated with particle-induced carcinogenesis. PAHs are agonists for AhR and are predominantly responsible for lung cancer through induction of highly carcinogenic metabolites. PAH metabolization requires CYP1A1 induction through activation of AhR, and therefore we hypothesized that carcinogenesis due to PAHs in APM would be reduced in AhR-/- mice. To examine this hypothesis, we performed a long-term continuous-application study of carcinogenesis in AhR-/- mice using airborne particulate extract (APE) of APM collected in Sapporo. Tumor development (squamous cell carcinoma) occurred in 8 of 17 AhR+/+ mice (47%), but no tumors were found in AhR-/-mice, and CYP1A1 was induced in AhR+/+ mice but not in AhR-/- mice. These results demonstrate that AhR plays a significant role in APE-induced carcinogenesis in AhR+/+ mice and CYP1A1 activation of carcinogenic PAHs is also of importance. Therefore, measurement of CYP1A1 induction in vitro may be useful for assessment of APM-induced carcinogenesis in humans. We also show that PAH-like compounds are major contributors to AhR-mediated carcinogenesis, whereas TCDD and related compounds make a smaller contribution.


Subject(s)
Neoplasms/pathology , Particulate Matter/toxicity , Receptors, Aryl Hydrocarbon/metabolism , Animals , Cytochrome P-450 CYP1A1/biosynthesis , Cytochrome P-450 CYP1A1/genetics , Dioxins/analysis , Enzyme Induction/drug effects , Genotype , Mice , Mutagenesis/drug effects , Particulate Matter/chemistry , Polycyclic Aromatic Hydrocarbons/analysis , Receptors, Aryl Hydrocarbon/deficiency , Skin/drug effects , Skin/enzymology
19.
Arterioscler Thromb Vasc Biol ; 27(5): 1199-205, 2007 May.
Article in English | MEDLINE | ID: mdl-17322098

ABSTRACT

BACKGROUND: Inhibition of GPVI has been proposed as a useful antithrombotic strategy; however, in vivo proof-of-concept animal studies targeting GPVI are lacking. We evaluated a novel anti-human GPVI monoclonal antibody OM4 Fab in rats. METHODS AND RESULTS: OM4 Fab specifically inhibited collagen-induced aggregation of rat platelets in vitro with an IC50 of 20 to 30 microg/mL but not ADP and AA-induced platelet aggregation. After intravenous administration of OM4 Fab, a rapid inhibition of ex vivo platelet aggregation was observed with a gradual recovery within 60 to 90 minutes which corresponded to the decline in OM4 Fab plasma concentration and time-dependent decrease in platelet-bound OM4 Fab. In contrast to previous reports in mice, intravenous OM4 Fab did not deplete platelet GPVI. Injection of OM4 IgG caused acute thrombocytopenia. In a modified Folts model of cyclic flow reduction in rat carotid artery, the number of complete occlusions was significantly reduced by intravenous administration of OM4 Fab (20 mg/kg) before or after mechanical injury to the vessel, without prolongation of bleeding time. CONCLUSION: Fab fragment of the monoclonal antibody OM4 effectively inhibits collagen induced platelet aggregation in vitro and ex vivo, and in vivo thrombosis in rats without prolonging bleeding time. Antibodies against GPVI may have therapeutic potential, inhibiting thrombosis without prolonging bleeding time.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Hemorrhage/epidemiology , Immunoglobulin Fab Fragments/immunology , Immunoglobulin G/immunology , Platelet Aggregation/drug effects , Platelet Membrane Glycoproteins/antagonists & inhibitors , Thrombosis/prevention & control , Animals , Antibodies, Monoclonal/administration & dosage , Bleeding Time , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Hemorrhage/etiology , Incidence , Injections, Intravenous , Platelet Count , Platelet Membrane Glycoproteins/metabolism , Rats , Risk Factors , Thrombosis/blood , Thrombosis/immunology
20.
Thromb Res ; 119(3): 319-29, 2007.
Article in English | MEDLINE | ID: mdl-16566959

ABSTRACT

Recent progress in the understanding of thrombus formation has suggested an important role for glycoprotein (GP) VI in this process. To clarify the exact role in detail, it is necessary to use specific, high affinity inhibitory antibodies. However, possibly due to the conserved structure of GPVI among species, it has been difficult to obtain potent antibodies. In this study, we developed highly potent anti-human GPVI monoclonal antibodies using GPVI knockout mice for immunization. Fab fragments of these antibodies, named OM1 and OM2, potently inhibit collagen-induced platelet aggregation. The IC(50) values for OM1 and OM2 are 0.6+/-0.05 and 1.7+/-0.5 microg/mL, respectively, showing potency greater than, or equal to that of abciximab (1.7+/-0.3 microg/mL), an anti-GPIIb/IIIa antibody. Fab fragments of OM1 and OM2 also potently inhibit collagen-induced ATP release, thromboxane A(2) formation, and platelet adhesion to immobilized collagen under static and flow conditions. Interestingly, platelet aggregation induced with collagen-related peptide was potently inhibited by OM2 but not OM1, indicating that OM1 recognizes an epitope that is different from collagen-related peptide-binding site on GPVI. These results suggest that OM1 and OM2 may be useful tools to understand the role of GPVI in thrombus formation. Furthermore, these antibodies have the potential to be developed as a new class of therapeutic tool.


Subject(s)
Antibodies, Monoclonal/pharmacology , Immunoglobulin Fab Fragments/pharmacology , Platelet Adhesiveness/drug effects , Platelet Aggregation/drug effects , Platelet Membrane Glycoproteins/immunology , Animals , Antibodies, Monoclonal/immunology , Antibody Specificity/immunology , Blood Platelets/cytology , Blood Platelets/metabolism , COS Cells , Chlorocebus aethiops , Humans , Immunization , Immunoglobulin Fab Fragments/immunology , Mice , Mice, Knockout , Platelet Adhesiveness/immunology , Platelet Aggregation/immunology , Platelet Membrane Glycoproteins/deficiency
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