Biomedical subjects

T Hiratsuka

Publications and source records attributed to T Hiratsuka.

At least 19 recordsLinked to original sources

PubMed2006

Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia.

Human beta-defensin (hBD)-3, a 45 amino acid antimicrobial peptide, was originally isolated from human skin. hBD-3 mRNA has also been detected in the airways by RT-PCR. While hBD-3 may be involved in antimicrobial defences within the respiratory tract, the presence of hBD-3 peptide in the respiratory system has not yet been confirmed. The antimicrobial activity of the synthesised hBD-3 peptide was measured by a radial diffusion assay and a colony count assay. The present authors confirmed the presence of hBD-3 peptide in homogenates of human lung and serum using reverse-phase HPLC coupled with a highly sensitive RIA. The localisation of the hBD-3 peptide was investigated by immunohistochemistry. In addition, the serum concentrations of hBD-3 were measured by RIA. hBD-3 exhibited a strong antimicrobial activity, which was unaffected by increasing salt concentrations. Immunohistochemically, the current authors observed the expression of hBD-3 in bronchial and bronchiolar epithelial cells. The mean+/-sd serum concentration of hBD-3 in patients with bacterial pneumonia was 239.4+/-17.8 pg x mL(-1) in the acute phase and, decreased to 159.3+/-20.1 pg x mL(-1) after the completion of therapy. In conclusion, these findings will help elucidate the role of human beta-defensin-3 in host immune responses and identify the pathophysiological significance of this molecule in respiratory infections.

Adult↗

PubMed2005

Implications of corpus gastritis, atrophy and cyclooxygenase in the development of gastric erosions after curing Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication decreases recurrence of peptic ulcers with marked improvement in histological inflammation, but gastric mucosal injuries may be developed even after eradication. PURPOSE: To investigate the mechanisms responsible for the development of gastric erosions after eradication, we analysed the relationship between clinicopathological risk factors and the occurrence of gastric erosion after curing H. pylori infection. PATIENTS: Sixty patients underwent endoscopy before, and 3, 6 and 12 months after the completion of H. pylori eradication. METHODS: Risk factors associated with the development of gastric erosions after eradication were assessed by multivariate analysis, and cyclooxygenase-1 and -2 immunoreactivity was histologically examined in the gastric mucosa before and after eradication. RESULTS: The cumulative prevalence of gastric erosions after H. pylori eradication was 38.3% within 1 year. Using multivariate analysis, corpus gastritis scores (inflammation score+activity score), corpus atrophy scores and an age of more than 50 years were found to be independent factors associated with the development of gastric erosion after eradication with odds ratios of 7.39, 0.13 and 5.00, respectively. Cyclooxygenase-2 immunoreactivity of the corpus was decreased for the non-erosion group after eradication, but not for the erosion group. CONCLUSIONS: Severe gastritis or less severe atrophy in oxyntic glands but not in pyloric glands before eradication may be involved in the development of gastric erosions after curing H. pylori infection.

Age Factors↗

PubMed2005

Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in Japanese patients with rheumatoid arthritis: the current situation and a prospective controlled-study of the preventive effects of lansoprazole or famotidine.

BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells.

BACKGROUND: and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation. METHODS: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry. RESULTS: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related. CONCLUSIONS: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.

Blotting, Western↗

PubMed2003

Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis.

BACKGROUND: Human beta-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of beta-defensins in cystic fibrosis, suggesting that beta-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by Pseudomonas aeruginosa. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease. METHODS: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB. RESULTS: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1beta. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles. CONCLUSIONS: These results indicate that beta-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.

Adult↗

PubMed2002

Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. AIM: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. METHODS: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. RESULTS: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. CONCLUSIONS: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.

Biopsy↗

PubMed2002

Inhibition of Helicobacter pylori-induced cyclo-oxygenase-2 aggravates NSAID-caused gastric damage in Mongolian gerbils.

BACKGROUND: The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial. AIM: To examine the effect of the interaction between H. pylori and non-steroidal anti-inflammatory drugs on gastric mucosal injury. METHODS: Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo-oxygenase proteins were determined by Western blot analysis and cyclo-oxygenase activity. RESULTS: A 2-day course of indometacin did not cause an increase in gastric damage in H. pylori-infected Mongolian gerbils compared to uninfected gerbils, while a 7-day course of indometacin caused additive gastric damage in H. pylori-infected animals. H. pylori infection induced cyclo-oxygenase-2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo-oxygenase activity in H. pylori-infected animals, while treatment for 7 days inhibited both cyclo-oxygenase-1 and cyclo-oxygenase-2 activities. Pre-treatment with a selective cyclo-oxygenase-2 inhibitor aggravated mucosal injury in H. pylori-infected animals treated or not treated with indometacin for 2 days. CONCLUSIONS: Our results suggest that cyclo-oxygenase-2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non-steroidal anti-inflammatory drugs. Therefore, inhibition of cyclo-oxygenase-2 activity may enhance non-steroidal anti-inflammatory drug-caused gastric damage in H. pylori-infected animals.

Animals↗

PubMed2002

Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Neutrophils are thought to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Human neutrophils contain antimicrobial and cytotoxic peptides in the azurophil granules which belong to a family of mammalian neutrophil peptides named alpha-defensins. A study was undertaken to investigate the role of alpha-defensins in the pathogenesis of IPF. METHODS: The concentrations of alpha-defensins (human neutrophil peptides (HNPs) 1, 2, and 3) in plasma and bronchoalveolar lavage (BAL) fluid of 30 patients with IPF and 15 healthy subjects were measured by radioimmunoassay. RESULTS: The concentrations of alpha-defensins in plasma, but not in BAL fluid, were significantly higher in IPF patients than in controls. BAL fluid concentrations of interleukin (IL)-8 in patients with IPF, which were significantly higher than in controls, correlated with those of alpha-defensins. An inverse relationship was seen between plasma alpha-defensin levels and the arterial oxygen tension (PaO(2)) and pulmonary function (vital capacity (%VC), forced expiratory volume in 1 second (FEV(1)), and carbon monoxide transfer factor (%TLCO)) in patients with IPF. Plasma levels of alpha-defensins also correlated with the clinical course in IPF patients with an acute exacerbation. Immunohistochemically, positive staining was observed inside and outside neutrophils in the alveolar septa, especially in dense fibrotic areas. CONCLUSION: These findings suggest that alpha-defensins play an important role in the pathogenesis of IPF, and that the plasma alpha-defensin level may be a useful marker of disease severity and activity.

Bronchoalveolar Lavage Fluid↗

PubMed2001

Nucleotide sequence and expression of rat beta-defensin-1: its significance in diabetic rodent models.

beta-Defensins are epithelium-derived antimicrobial peptides that function in the host's innate defense. We identified the first member of the rat beta-defensin family, beta-defensin-1 (BD-1), in the kidney and determined its nucleotide sequence. It was predicted to be a 37-amino-acid peptide. Rat BD-1 mRNA was expressed most abundantly in the kidney, next in skin, tongue, esophagus, and uterus, followed (at low levels) by brain, trachea, stomach, urinary bladder, and ovary. BD-1 gene expression in rat kidney was not increased by lipopolysaccharide administration. BD-1 gene expressions in the kidneys of diabetic rodent models, cholecystokinin-insensitive Otsuka Long-Evans Tokushima Fatty rats, leptin-insensitive obese (fa/fa) Wistar rats, and db/db mice, were significantly lower than those of their lean littermates. BD-1 reduction may be in part responsible for the high incidence of urinary tract infections in diabetes mellitus.

Amino Acid Sequence↗

PubMed2001

Case report: Hypoechoic area as an ultrasound finding suggesting subserosal invasion in polypoid carcinoma of the gall bladder.

Ultrasound studies have demonstrated the gall bladder wall to consist of two or more (usually three) layers. Gall bladder tumours with neither a thinned nor split outermost hyperechoic layer are confined to the mucosa or muscle layer, or have only invaded the shallow subserosa. Differentiation of these two types of tumour has posed difficulties. We report a case of polypoid gall bladder carcinoma invading the shallow subserosa with a thickened outermost hyperechoic layer but a hypoechoic area in the deeper part of the tumour. Ultrasound and pathological correlation in this case demonstrated that the hypoechoic area represented an adenocarcinoma invading the subserosa accompanied by abundant fibrosis.

Adenocarcinoma, Papillary↗

PubMed2001

Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection.

STUDY OBJECTIVES: To investigate the roles of human alpha-defensin (HAD), human beta-defensin (HBD)-1, and HBD-2, novel antimicrobial peptides, in patients with Mycobacterium avium-intracellulare infection (MAI). PATIENTS: The study included 25 patients (10 men) with MAI who visited our hospital between June 1998 and August 1999. MEASUREMENTS AND RESULTS: In patients with pulmonary MAI, we measured HAD and HBD-1, and HBD-2 levels in plasma and in BAL fluid (BALF) by radioimmunoassay. Plasma concentrations of HAD and HBD-2 in those patients were higher than those in control subjects, whereas HBD-1 levels were similar to those in the control subjects. High levels of HAD and HBD-2, but not HBD-1, also were observed in the BALF of MAI patients. There was a positive correlation between HAD and interleukin (IL)-8 concentrations in the BALF of patients with MAI. BALF HBD-2 concentrations also correlated positively with those of plasma HBD-2 and BALF IL-1 beta in MAI patients. Patients with cavity formation on the chest roentgenogram had higher HAD and HBD-2 levels in their BALF than those of patients without cavity formation. Treatment with clarithromycin combined with two or three other antibiotics, including ethambutol, rifampicin, ofloxacin, or ciprofloxacin, for at least 6 months resulted in a significant fall in plasma HBD-2 concentrations in responders, but not in nonresponders. CONCLUSION: Our findings suggest that HAD and HBD-2 may participate in host defense and local remodeling of the respiratory tract in patients with MAI and that plasma HBD-2 levels may be a useful marker of disease activity in patients with pulmonary MAI.

Anti-Bacterial Agents↗

PubMed2001

[Beta-defensins in plasma and bronchoalveolar lavage fluid in patients with non-tuberculous mycobacterium infection].

We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with with non-tuberculous mycobacterium infection (NTM). Plasma HBD-2 levels in NTM patients before treatment were higher than those in the controls, while the HBD-1 levels were similar to the control levels. High levels of HBD-2, but not of HBD-1, in BALF were also observed in NTM patients. In NTM, a positive correlation was found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1 beta levels in BALF. NTM patients with cavities or ectasia on chest radiography had higher HBD-2 levels in BALF than those without. Plasma HBD-2 levels in NTM patients were markedly decreased after successful treatment, while those of patients with an intractable mycobacterium infection maintained the same high plasma HBD-2 levels as those before treatment. These findings suggest that HBD-2 may participate in the host defense and plasma HBD-2 levels may reflect disease activity in pulmonary NTM.

Biomarkers↗

PubMed2001

[A case of bird fanciers' disease caused by parrot droppings].

A 50-year-old woman who had been treated for Parkinson's disease was admitted to our hospital because of exertional dyspnea and weight loss. Her chest computed tomography showed diffuse ground glass opacities in both lung fields. Bronchofiberscopy was performed, and the bronchoalveolar lavage fluid showed an elevated lymphocyte count. The serum Ouchterlony test yielded positive results for parrot droppings as well as for pigeon serum and droppings. She had had a parrot for several years, but no pigeon, and so we diagnosed bird fanciers' disease associated with parrot droppings. This responded well to steroid therapy. This case of bird fanciers' disease was caused by the droppings of only one parrot.

Animals↗

PubMed2000

[A case of severe Legionnaires' disease complicated by rhabdomyolysis, acute renal failure, liver dysfunction and encephalopathy].

A 67-year-old male was admitted to our hospital due to a high fever with abnormal shadows on chest X-ray films. On admission, his laboratory data showed hyponatremia, rhabdomyolysis and liver dysfunction. Encephalopathy, acute renal failure and respiratory failure developed, despite fluid management and antimicrobial therapy. His condition worsened rapidly in a few days enough to require mechanical ventilation. Legionnaires' disease was suspected, because pneumonia was found to be associated with multiple organ dysfunction. Intravenous erythromycin and methylprednisolone were administered. The patient's condition was rapidly improved, although he needed hemodialysis for 30 days. Later, indirect fluorescent antibody testing of the patient's serum against Legionella pneumophila was definitely positive (1:1024). We reported the first case of severe Legionnaires' disease in Miyazaki Prefecture, Japan.

Acute Kidney Injury↗

PubMed2000

Structural analysis of human beta-defensin-1 and its significance in urinary tract infection.

Human beta-defensin-1 (hBD-1) is a 36-amino-acid antimicrobial peptide that functions in the host innate defense. We developed a highly sensitive radioimmunoassay for hBD-1 and identified several hBD-1 peptides in human kidney, urine, and plasma by amino acid sequencing and mass spectrometry. Large quantities of hBD-1 peptides are produced in the kidney, are released into the tubular lumen as 47-amino-acid pro-hBD1, and then undergo proteolytic processing and generate multiple truncated forms. The respective urine and plasma concentrations of hBD-1 in patients with pyelonephritis are 48.1 +/- (SEM) 15.7 pmol/mg creatinine and 2.66 +/- 0.41 pmol/ml, 3.1-fold and 1.8-fold those of normal individuals. hBD-1 is thought to contribute to mucosal defense in the urinary tract. Our findings provide a better understanding of the biosynthesis of this peptide and its pathophysiological significance in infectious diseases.

Adult↗

PubMed2000

[Pulmonary dirofilariasis with cavity formation and pleural effusion].

A 61-year-old man visited a community hospital because of hemosputum. A solitary nodule in the left lower lung field was pointed out on a chest roentgenogram. The patient was treated with antibiotics, but the solitary nodule increased in size. He was referred to our hospital because of high fever and observations of cavity formation and pleural effusion on a chest roentgenogram. The pleural effusion showed no cytologic evidence of malignancy, and cultures were also negative for bacteria. An increased percentage of lymphocytes was detected in the pleural effusion, but slight eosinophilia was found in blood samples. Dot enzyme-linked immunosorbent assay and Ouchterlony's double-diffusion test yielded a diagnosis of pulmonary dirofilariasis. After drainage of the pleural effusion by thoracentesis, spontaneous regression was observed. Cavity formation, pleural effusion, and spontaneous regression are in general rare in patients with pulmonary dirofilariasis.

Dirofilariasis↗

PubMed2000

[Bronchial atresia with atelectasis of the left upper lobe].

A 69-year-old woman visited her physician on October 1 complain of dry cough. However, the chest radiograph revealed no abnormalities. She was later admitted to our hospital because a radiograph taken by another physician on November 26 revealed a massive lesion in the right upper mediastinum. Computed tomographic findings showed a massive lesion containing a branching structure with a few calcifications, suggesting a case of atelectasis of the left upper lobe with mucus plug. Bronchoscopic examination revealed complete obstruction of the orifice of the left upper lobe bronchus, and so a diagnosis of bronchial atresia was made. However, since the patient had a history of tuberculous peritonitis and the mass lesion was somewhat calcified, the possibility that this was an acquired case could not be ruled out. After treatment with oral antibiotics, the size of the atelectasis was decreased. Therefore, we considered that the expansion of the atelectasis could have been due to superimposed bacterial infection.

Aged↗

PubMed2000

[A case of paragonimiasis westermani with a high level of interleukin 5 in bronchoalveolar lavage fluid].

A 49-year-old man was admitted to our hospital with a productive cough and bloody sputum. Peripheral blood eosinophil counts and serum IgE values were elevated. Chest radiography and chest computed tomography revealed a solitary nodule with cavitation and satellite lesions in the right middle lobe, in contact with the pleura. The diagnosis of paragonimiasis westermani was confirmed by detection of ova in the sputum and bronchoalveolar lavage fluid (BALF) samples, and by immunoserological examination. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After treatment, his clinical symptoms and radiological abnormalities disappeared. The IL-5 level was high in BALF, but it was undetectable in the plasma, suggesting that IL-5 in inflammatory lesions may be particularly important in mediating eosinophilia in the blood and BALF in paragonimiasis westermani.

Anthelmintics↗