Gastric hamartomatous polyposis, Cowden syndrome, and H. pylori.
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Adult↗
Biomedical subjects
Shigeru Kohno
Publications and source records attributed to Shigeru Kohno.
Formation of two aneurysms from a coronary artery-pulmonary artery fistula.
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Arterio-Arterial Fistula↗
[Nephrotic syndrome after bee stings].
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Adult↗
Cysteinyl leukotrienes regulate dendritic cell functions in a murine model of asthma.
Dendritic cells (DCs) act as APCs in the airway and play a critical role in allergy. Cysteinyl leukotrienes (cysLTs) synthesized from arachidonic acid are primary mediators of immediate asthmatic reaction. The aim of this study was to investigate the effects of cysLTs on Dermatophagoides farinae (Der f)-pulsed mouse myeloid DCs in inducing allergic airway inflammation in vitro and in vivo. Control DC (medium-pulsed), Der f-pulsed DC, cysLT-pulsed DC, Der f- and cysLT-pulsed DC, and Der f-pulsed and cysLT receptor antagonist (LTRA)-treated DC were prepared from murine bone marrow, and the production of cytokines ws compared. Subsequently, these DCs were intranasally instilled into another group of naive mice, followed by intranasal Der f challenge to induce allergic airway inflammation in vivo. Der f-pulsed DC produced significantly higher amounts of IL-10 and IL-12 compared with control DC. Der f- and cysLT-pulsed DC further increased IL-10 production compared with Der f-pulsed DC. In contrast, treatment of Der f-pulsed DC with LTRA increased IL-12 and decreased IL-10. Intranasal instillation of Der f-pulsed DC resulted in airway eosinophilia associated with a significant rise in IL-5 levels in the airway compared with control DC. Pulmonary eosinophilia and excess IL-5 were further enhanced in Der f- and cysLT-pulsed DC-harboring mice. In contrast, Der f-pulsed and LTRA-treated DC significantly inhibited airway eosinophilia, reduced IL-5, and increased IFN-gamma in the airway. Our results suggest that cysLTs play an important role in the development of allergic airway inflammation by regulating the immunomodulatory functions of DCs.
5-Lipoxygenase-Activating Proteins↗
Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic.
Breast cancer resistance protein (BCRP/ABCG2) of an ATP-binding cassette half-transporter confers resistance against mitoxantrone and camptothecin derivatives of topotecan and irinotecan. Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro and in vivo, the mechanism of which remains undetermined. Here we focused on drug efflux pump and examined whether novobiocin reversed drug resistance in multidrug-resistant cells highly expressing BCRP. To explore the reversal mechanisms, intracellular drug accumulation was measured by flow cytometry, and a topotecan transport study using plasma membrane vesicles was performed. We used PC-6/SN2-5H2 small cell lung cancer and MCF-7/MX breast cancer cells selected with SN-38 of the active irinotecan metabolite and mitoxantrone, respectively, and the BCRP cDNA transfectant MCF-7/clone 8 cells. These cells expressed high levels of BCRP mRNA but not other known transporters. Compared to the parental PC-6 cells, PC-6/SN2-5H2 cells were 141-, 173- and 57.2-fold resistant to topotecan, SN-38 and mitoxantrone, respectively. Novobiocin at 60 microM decreased the degree of the above resistance by approximately 26-fold in PC-6/SN2-5H2 cells, and similarly reversed resistance in MCF-7/MX, MCF-7/clone 8 and un-selected NCI-H460 cells highly expressing BCRP. Furthermore, novobiocin increased the intracellular topotecan accumulation in these cells and inhibited the topotecan transport into the membrane vesicles of PC-6/SN2-5H2 cells. No effects of novobiocin in these assay were observed in the parental PC-6 and MCF-7 cells. The kinetic parameters in the transport study indicated that novobiocin was a inhibitor for BCRP, resulting in competitive inhibition of BCRP-mediated topotecan transport. These findings suggest that novobiocin effectively overcomes BCRP-mediated drug resistance at acceptable concentrations.
ATP Binding Cassette Transporter, Subfamily G, Mem↗
Evaluation of venous thromboembolism and coagulation-fibrinolysis markers in Japanese patients with inflammatory bowel disease.
BACKGROUND: Arterial or venous thromboembolism is rarely encountered clinically as an extradigestive tract complication in inflammatory bowel disease (IBD). However, it is one of the important prognostic factors for IBD patients. The present study was designed to evaluate the relationship between pulmonary embolism (PE) and deep vein thrombosis (DVT) with coagulation-fibrinolysis markers in patients with active IBD. METHODS: In 47 consecutive cases hospitalized due to active IBD [26 with Crohn's disease (CD) and 21 with ulcerative colitis (UC)], we evaluated the disease severity, blood tests, pulmonary ventilation-perfusion scan (V/Q scan), and magnetic resonance venography (MRV) or conventional venography. RESULTS: PE was diagnosed by V/Q scan in 5 (2 with CD and 3 with UC; 10.6%). DVT was diagnosed in 5 (2 with CD and 3 with UC; 10.6%). Of the 47 patients, 8 (17.0%) had venous thromboembolism (either PE or DVT), and 2 of them (4.3%) had both conditions. In UC patients, the thrombosis group was in more severe stages based on endoscopic grading than the nonthrombosis group. In all patients, the thrombosis group were older (50.3 +/- 14.3 years) than the nonthrombosis group (29.2 +/- 11.7 years). Furthermore, the thrombosis group had higher thrombin-antithrombin III complex (13.1 +/- 17.7 ng/ml) and d-dimer (964 +/- 1402 ng/ml) values than the nonthrombosis group (5.3 +/- 5.5 ng/ml, P=0.0245, and 207 +/- 192 ng/ml, P=0.0016, respectively). There were no significant differences in leukocyte and platelet counts, C-reactive protein, and fibrinogen between the two groups. CONCLUSIONS: A high incidence of venous thromboembolism was suggested in Japanese patients with active IBD. We should be careful with thrombosis in treatment of IBD patients, especially those who are of older age and in more severe stages.
Adult↗
High-risk populations for nasal carriage of methicillin-resistant Staphylococcus aureus.
To determine the population at high risk of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) on hospital patients admission, a nasal swab was taken from the following patients: (1) those aged 70 years or over (age >or= 70), (2) non ambulatory receiving regular home visits by nurses and physicians (visiting), (3) residents of nursing homes (nursing home), (4) patients from other hospitals (another Hp), and (5) those scheduled for surgery (presurgery). Between March and July 2000, a total of 412 patients were admitted and 136 were enrolled. MRSA was isolated from 12 (8.8%) patients. The number of patients positive for MRSA in the five groups, age >or=70, visiting, nursing home, another Hp, and presurgery, were 3 of 68, 3 of 21, 2 of 3, 3 of 9, and 1 of 35, respectively. Multivariate analysis revealed that living in a nursing home [odds ratio (OR) = 32.82, P = 0.010] or coming from another hospital (OR = 14.55, P = 0.0043) were high risk factors with for nasal carriage of MRSA. Furthermore, patients' ages were further divided into three categories, or=90, and regarded as independent high risk factors (OR = 3.08, P = 0.043). The results were that advanced living in a age (>or=80, >or=90), living in a nursing home or coming from another hospital are high risk factors of nasal carriage of MRSA on hospital admission.
Adult↗
Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy.
We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.
Acute Disease↗
Evaluation of the contemporary occurrence rates of metallo-beta-lactamases in multidrug-resistant Gram-negative bacilli in Japan: report from the SENTRY Antimicrobial Surveillance Program (1998-2002).
Metallo-beta-lactamases (M beta L) were initially characterized in Japan, usually of the IMP-type, and found in Pseudomonas aeruginosa (PSA), Acinetobacter spp. (ACB), or Serratia marcescens (SM). The number of M beta L types has increased worldwide, but geographic dissemination within Japan has appeared limited. This study compares baseline levels of M beta L resistance from two 22-center studies (1996-1997) to the longitudinal sample (3 sites) of Japanese isolates from the SENTRY Antimicrobial Surveillance Program (1998-2002). All minimal inhibitory concentration results were determined by reference methods. A total of 26.8% PSA, 3.4% ACB, and 3.1% Enterobacteriaceae (enterobacters and SM) with resistance to monitored carbapenems (CARB) (minimal inhibitory concentration, > or =8 microg/mL) were screened for M beta L production by disk approximation tests (EDTA and 2-MPA inhibitors), CARB hydrolysis by enzyme extracts, and selected PCR primers for known M beta L types. All M beta L-positive strains (10) were sequenced to determine enzyme identification. Clonality in each center was determined by automated ribotyping and PFGE. The CARB susceptibility rates in PSA decreased (80.7% to 62.0%) over the monitored interval (1998-2002), but varied by medical center location. Among CARB-resistant isolates, 10.8% were attributed to M beta L strains (1.1% of all PSA tested). M beta L identification showed the following: five PSA (three IMP-1, two IMP-2), four SM (one IMP-1, two IMP-1 + OXA-1, and one IMP-11). Also a single ACB had an IMP-1. Eight of 10 M beta L isolations occurred between 2000 and 2002; four occurred in 2002. BRL42715, an AMP-C inhibitor, confirmed AMP-C-mediated resistance in 87.3% of PSA, and outer membrane protein changes were also discovered by membrane studies. Prior results (22 sites, 1997-1998) showed CARB resistance at 22.4-25.6% and 0.5-0.9% M beta Ls (IMP-1) overall; it was slightly elevated in this SENTRY Program sample. In conclusion, M beta L-producing strains from several species persist in Japan, but represent a distinct minority of all CARB-resistant strains (1998-2002). Although M beta L rates appear generally stable in Japan, continued surveillance for these mechanisms seems to be a prudent practice, because of the mobility of the genetic determinants and the emergence of novel enzyme types, especially among the Enterobacteriaceae.
Amino Acid Sequence↗
Macrolide antibiotics induce apoptosis of human peripheral lymphocytes in vitro.
We previously reported that long-term administration of macrolides (MCL) reduced the number of lymphocytes in bronchoalveolar lavage fluid (BALF) of patients with chronic lower respiratory tract disease. To investigate the anti-inflammatory activity of macrolides, we evaluated their effect on apoptosis of lymphocytes isolated from human peripheral blood. Lymphocytes treated with clarithromycin, azithromycin and josamycin at a final concentration of 200 microg/ml showed positive staining for Annexin V, Fas and Fas ligand using flow cytometry with time at 12-72 h, while other antibiotics did not. Our results suggest that macrolides induce apoptosis of lymphocytes through Fas-Fas ligand pathway and could potentially reduce the number of lymphocytes in the lungs of patients with chronic lower respiratory tract disease.
Annexin A5↗
Efficacy of long-term macrolide antibiotic therapy in patients with diffuse panbronchiolitis: comparison between HLA-B54-positive and -negative cases.
This study compared the clinical characteristics and the effects of long-term macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients with diffuse panbronchiolitis (DPB). Thirty-two Japanese patients were enrolled who had the clinical criteria for DPB. All patients received long-term macrolide therapy, and therapeutic results were compared according to the presence or the absence of HLA-B54 antigen. Clinical, laboratory, radiological and bacterial features were strikingly similar in both groups before macrolide therapy. Long-term treatment with macrolides improved clinical symptoms, PaO(2), and forced expiratory volume in 1s (FEV(1)) equally in both groups. This study indicates that genetic susceptibility may not explain the pathogenesis of DPB, and that low-dose macrolide therapy can achieve clinical improvement irrespective of genetic predisposition in DPB.
Adult↗
The use of a hydrophilic-coated catheter during transradial cardiac catheterization is associated with a low incidence of radial artery spasm.
BACKGROUND: Radial artery spasm (RAS) is a common complication of transradial approach (TRA) to percutaneous coronary angiography (CAG) and coronary intervention. Lower friction resistance between catheter and RA wall may reduce RAS upon insertion, manipulation, and withdrawal of the catheter. The aim of this study was to investigate whether the use of a hydrophilic-coated (HC) catheter, which has lower friction coefficient, could reduce the incidence of RAS compared with a non-hydrophilic-coated (NHC) catheter. METHODS: A total 250 patients attempted diagnostic CAG using 5-French catheters via the TRA between September 2000 and April 2002. Two hundred thirty-four (93.6%) patients who achieved successful coronary cannulation were selected for the study. NHC catheters were used in 149 patients (63.7%), and HC catheters were used in 85 patients (36.3%). We compared the incidence of RAS between NHC and HC catheters. RESULTS: RAS occurred in 17 (7%) patients totally. RAS was less likely to occur in HC group (one patient, 1%) than in the NHC group (16 patients, 11%, P = 0.007). CONCLUSIONS: We conclude that the use of HC catheters can reduce RAS upon insertion, manipulation, and withdrawal of the catheter compared with NHC catheters.
Angioplasty, Balloon, Coronary↗
Effects of antiasthmatic agents on the functions of peripheral blood monocyte-derived dendritic cells from atopic patients.
BACKGROUND: Dendritic cells (DCs), the antigen-presenting cells in the airway, play a critical role in asthma. Nevertheless, there is little information on the effects of antiasthmatic agents on DCs. OBJECTIVES: The purpose of the present study was to determine the effects of representative antiasthmatic agents, including cysteinyl leukotriene (cysLT) 1 receptor antagonists, corticosteroid, and tacrolimus, on DCs in inducing allergy. METHODS: Human peripheral blood monocyte-derived DCs (MoDCs) generated from atopic and healthy subjects were pulsed with Dermatophagoides farinae allergen in the presence of medium alone, pranlukast, montelukast, dexamethasone, or tacrolimus. The mRNA expressions of cysLT receptor, cysLTs producing enzymes, and various surface markers on MoDCs, as well as the concentrations of cysLTs, IL-10, and IL-12 in cultured supernatants, were determined. MoDCs were also cocultured in vitro with autologous CD4(+) T cells, and IL-5 and IFN-gamma production was measured. RESULTS: MoDCs of atopic patients expressed mRNAs of cysLT1 receptor and cysLT-producing enzymes, and allergen pulsing significantly increased cysLT production. MoDCs of atopic patients showed a T(H)2-favoring phenotype and induced T(H)2-skewed cytokine production from autologous CD4(+) T cells. Dexamethasone and tacrolimus inhibited allergen-pulsed MoDC-induced cytokine production by autologous CD4(+) T cells without and with IL-10 inhibition, respectively. CysLT1 receptor antagonists had no effect on MoDC functions. CONCLUSION: Our results indicate that MoDCs of atopic patients induce a T(H)2 reaction. Corticosteroid and tacrolimus, but not cysLT1 receptor antagonists, inhibit T(H)2 reactions, and this effect is probably mediated through different pathways.
Adrenal Cortex Hormones↗
Tacrolimus reduces urinary excretion of leukotriene E(4) and inhibits aspirin-induced asthma to threshold dose of aspirin.
BACKGROUND: The exact mechanism of aspirin-induced asthma is not clear. It has been postulated that precipitation of asthma attacks by aspirin is linked to inhibition of COX activity and massive release of cysteinyl leukotriene into the airway. Tacrolimus, a macrolide-derived immunosuppressant, is used for immunosuppression in organ transplantation and also for allergic diseases such as atopic dermatitis. OBJECTIVE: We evaluated the effects of tacrolimus in aspirin-induced asthma by using a double-blind, crossover study design. METHODS: Twelve patients with aspirin-induced asthma (male:female, 3:9; mean age +/- SD, 36.7 +/- 7.2 years) received either tacrolimus (0.1 mg/kg) or placebo 2 hours before the threshold dose of oral aspirin. RESULTS: In the placebo arm, oral aspirin significantly decreased FEV 1 concomitant with significant increases in sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. Tacrolimus significantly inhibited bronchoconstriction and abrogated aspirin-induced increase in both sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. CONCLUSION: The current study suggested that tacrolimus inhibited bronchoconstriction to a threshold dose of aspirin by inhibition of cysteinyl leukotriene excretion.
ATP Binding Cassette Transporter, Subfamily B↗
Bronchobiliary fistula associated with intrahepatic biloma after transcatheter arterial chemoembolization for hepatocellular carcinoma.
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Aged↗
Soluble form of Fas and Fas ligand in serum and bronchoalveolar lavage fluid of individuals infected with human T-lymphotropic virus type 1.
Human T-lymphotropic virus type 1 (HTLV-1) carriers are known to develop pulmonary complications characterized by T-lymphocytic alveolitis. The aim of this study was to determine the profile and role of soluble Fas (sFas) and sFas ligand (sFasL) in the lung of asymptomatic HTLV-1 carriers. We measured sFas and sFasL levels in serum and bronchoalveolar lavage fluid (BALF) of 16 seropositive asymptomatic HTLV-1 carriers and 32 healthy subjects. The serum levels of both sFas and sFasL were significantly higher in HTLV-1 carriers than in the control. In BALF, the percentage of lymphocytes and CD4 positive T-cells, and the levels of sFasL were also significantly higher in asymptomatic carriers than the control, but there were no significant differences in sFas levels between the two groups. There was a significant correlation between BALF sFasL levels and serum sFasL levels and percentage of CD4 positive T-cells in BALF. Our results suggest that the increased levels of sFasL in the lung of asymptomatic HTLV-1 carriers are associated with accumulation of CD4 positive T-cells, and that resistance to apoptosis in HTLV-1 infected T-cells and overproduction of sFasL could contribute to T-lymphocytic alveolitis by down-regulating Fas-FasL mediated apoptosis.
Bronchoalveolar Lavage Fluid↗
Multiplex PCR for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila in community-acquired pneumonia.
A multiplex polymerase chain reaction (PCR) was developed for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. Oligonucleotide primers for the amplification of the DNA of these three organisms were optimized for use in combination in the same reaction. PCR products were detected by the Micro-Chip Electrophoresis Analysis System. Clinical samples were obtained from 208 community-acquired pneumonia (CAP) patients who were participants in a multicenter CAP surveillance study performed at seven medical schools and their affiliate hospitals in Japan. No significant differences in the sensitivity of each primer set were observed when tested in both the multiplex and monoplex PCR assays. Our multiplex PCR was able to reliably detect 10 copies/100 microl of each of the three pathogen DNAs. Of the panel of 208 samples, 14 of 15 C. pneumoniae, 10 of 10 M. pneumoniae, eight of eight L. pneumophila and 165 of 176 negative samples were correctly identified. Eleven cases who were the multiplex PCR positive and conventional method negative were observed. The PCR findings were of possible significance in at least four of these patients. Our multiplex PCR assay could potentially be used as a diagnostic and epidemiological tool. Further prospective studies are needed to establish its clinical usefulness.
Adolescent↗
High-BAL fluid concentrations of RANTES in nonspecific interstitial pneumonia compared with usual interstitial pneumonia.
Chemokines such as regulated on activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, monocyte inflammatory protein (MIP)-lalpha have been reported to play an important role in the pathogenesis of interstitial lung diseases. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia (NSIP) has elevated percentages of Lymphocytes in bronchoalveolar lavage (BAL) fluid compared with usual interstitial pneumonia (UIP). These chemokines are candidate mediators for lymphocyte attraction to the lung in NSIR Therefore, we measured the BAL fluid levels of RANTES, MCP-1 and MIP1-alpha in 15 patients with idiopathic NSIP, 20 with idiopathic UIP, 22 with sarcoidosis and 12 healthy volunteers to evaluate the contribution of these chemokines using enzyme-linked immunosorbent assays. The levels of RANTES in BAL fluid were significantly higher in patients with NSIP compared with healthy volunteers (P < 0.01), UIP and sarcoidosis (P < 0.05). In MCP-1, the levels in BAL fluid of NSIP and UIP patients were significantly elevated compared with healthy volunteers and sarcoidosis patients (P < 0.01). These results suggest that RANTES and MCP-1 in BAL fluid may play an important role in inflammatory cell recruitment to the lung in idiopathic NSIP as well as other interstitial lung diseases.
Bronchoalveolar Lavage Fluid↗