Second Department of Internal Medicine, *Department of Microbiology, and Department of Hospital Pathology, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, Japan
Corresponding author: ...Dr K. Yoshida (e-mail: kanako{at}med.toho-u.ac.jp ).
Received 3 Sept. 1999; revised version accepted 27 March 2000.
Abstract
The role of bacterial capsule in inflammatory responses in experimentally induced pneumonia caused by Klebsiella pneumoniae was evaluated by comparing the host immunological responses in mice infected with capsulate strain DT-S and non-capsulate mutant strain DT-X. Anaesthetised ICR mice were infected intranasally with inocula of strain DT-S or DT-X. Mice infected with strain DT-X survived significantly longer than those inoculated with strain DT-S. Viable bacterial counts in lungs and blood increased rapidly in mice infected with strain DT-S, in contrast to the gradual decrease in their density in lungs and intermittent bacteraemia in mice infected with strain DT-X. The number of broncho-alveolar lavage (BAL) cells in mice infected with strain DT-X at 24 h after inoculation was significantly higher than in those infected with strain DT-S. In the early stages of infection, the levels of tumour necrosis factor- and interleukin-6 in BAL fluid of mice infected with strain DT-X were significantly higher than those of mice infected with strain DT-S. In contrast, in the late stage of infection, the levels of these cytokines in serum of mice infected with strain DT-S were significantly higher than in mice infected with strain DT-X. These results suggest that K. pneumoniae capsule may suppress the host immunological responses, thus allowing the bacteria to grow, causing pneumonia, septicaemia and death.
Cancer cachexia, characterized by anorexia, weight loss and progressive tissue wasting, has been postulated to be mediated by various cytokines. However, the precise mechanism of cachexia induction ...is not fully explained. We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis-elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo as well as in vitro. This novel molecular strategy could be useful for treating a broad range of human diseases including cancer. In this study, we injected decoy ODN targeting the transcriptional factor, NF-kappa B (NF kappa B) binding cis-elements, which are essential for transactivation of gene expression of cytokines, directly into tumors of adenocarcinoma colon26 in mice, in order to examine whether or not cachexia is alleviated by inhibiting the action of cytokines. Tumor growth was not affected by transfection of NF kappa B decoy ODN as compared with scrambled decoy ODN. Nevertheless, transfection of NF kappa B decoy, but not scrambled decoy, ODN resulted in attenuation of the reductions in body weight, epididymal fat, gastrocnemius muscle mass and food intake, which were induced by the tumor presence. Interleukin 6 mRNA in the tumor was also markedly decreased by the transfection of NF kappa B decoy ODN. It is known that the transcriptional factor E2F plays a pivotal role in the coordinated transactivation of cell cycle regulatory genes. Therefore, we hypothesized that the introduction of synthetic double-stranded DNA with high affinity for E2F in vivo as 'decoy' cis-elements might inhibit the tumor growth of colon26, resulting in turn in inhibition of cachexia induction. However, injection of E2F decoy ODN failed to inhibit tumor growth and cachexia induction, as compared with mismatched decoy ODN. Overall, the present study demonstrated that cachexia induced by adenocarcinoma colon26 was inhibited by blocking of NF kappa B, using a novel molecular decoy strategy, without an effect on tumor growth, and also that tumor growth and cachexia induction in the colon26 model were not affected by E2F decoy ODN. These results suggest that cytokines regulated by NF kappa B may play a pivotal role in the induction of cachexia by colon26, providing a new therapeutic strategy for cancer cachexia.
Rheumatoid arthritis (RA) patients often take non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids as supportive drugs. In this study, we investigated the prevalence of endoscopic ...gastric damage and their prescribed medications under an actual clinical condition.
We collected the data of 1704 RA patients who underwent upper gastrointestinal fiberscopy. Gastric mucosal erosion and ulcer were classified using modified LANZA score. We analyzed these data with a multiple regression analysis.
The prevalence of endoscopic gastric mucosal damage in these RA patients was 16.7% (285 cases). A multiple regression analysis indicated that prednisolone (PSL), NSAIDs and proton pump inhibitors (PPIs) were independent risk factors associated with the modified LANZA score. PSL and NSAIDs were positively correlated with the score, while the administration of PPIs was inversely correlated with the score. The modified LANZA score in RA patients treated with both PSL and NSAIDs was significantly higher than that in those treated with PSL alone (no NSAIDs use).
Our findings suggest that PSL and NSAIDs were exacerbating factors for gastric mucosal damage, while PPIs usage was a protective factor. And, the combined usage of corticosteroids and NSAIDs may induce the development of gastric ulcers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Second Department of Internal Medicine, *Department of Microbiology, and Department of Hospital Pathology, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, Japan
Corresponding author: ...Dr K. Yoshida (e-mail: kanako{at}med.toho-u.ac.jp ).
Received 27 Sept. 2000; accepted 8 Nov. 2000.
Abstract
The role of the capsule of Klebsiella pneumoniae in inducing cytokine production was investigated by comparing the responses of mice with experimentally induced pneumonia caused by capsulate (strain DT-S) or non-capsulate (mutant strain DT-X) K. pneumoniae . Anaesthetised ICR mice were inoculated intranasally. Whereas all DT-S-infected mice died within 3 days, no deaths were observed in DT-X-infected mice by 14 days after infection. During the early stage of infection, interferon- (IFN- ) levels in broncho-alveolar lavage fluid (BALF) of DT-X-infected mice were significantly higher than those in DT-S-infected mice. In contrast, in the late stage of infection, serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and IFN- in DT-S-infected mice were significantly higher than those in DT-X-infected mice. Levels of interleukin-10 (IL-10) in BALF and serum of DT-S-infected mice were significantly and persistently higher than those of DT-X-infected mice. The IL-10/TNF- (tumour necrosis factor- ) ratios in BALF and serum indicated that higher levels of IL-10 production were induced in mice infected with strain DT-S than in those infected with strain DT-X. The results suggest that the capsule of K. pneumoniae may induce IL-10 production at the site of infection and, thereafter, these high IL-10 levels may serve to down-regulate the expression of pro-inflammatory cytokines.
Power spectral analysis of heart rate variability (HRV) using a fast Fourier transformation (FFT) is widely used to assess diet-related changes in cardiac autonomic balance. Although there are ...various HRV spectral analysis methods, no study compared the different HRV spectral analysis methods to evaluate diet-related cardiac autonomic balance. The aim of this study was to evaluate the effect of high-carbohydrate meal intake on HRV assessed by FFT and AR in healthy normal subjects. Ten healthy young male subjects aged 22-25 years old participated in this study. After recording baseline R-R intervals, further recordings were made continuously for 120 min after a test meal. We calculated the following frequency parameters of HRV: very low frequency power (VLF: 0.01-0.04 Hz), low frequency power (LF: 0.04-0.15 Hz), high frequency power (HF: 0.15-0.4 Hz), and LF/HF ratio. A consecutive 1,024-sec time series of R-R interval data obtained at 10-min intervals from the baseline was used to calculate HRV parameters. To compare the two different power spectral analysis methods, we examined intraclass correlation coefficients (ICC) and their 95% confidence intervals (CI). Statistical analysis was carried out using SPSS 15.0J. Mean ICC were high in 4 HRV parameters. Mean lower ICC 95% CI in all HRV parameters except for VLF power were >0.75. Our results suggest that there were few differences in LF power, HF power, and LF/HF ratio between FFT and AR in young male subjects. Further study is needed to confirm our results.
Rheumatoid arthritis (RA) is characterized by systemic synovitis with bone erosion and joint cartilage degradation. Although the analysis of polymorphisms in cytokine-encoding genes is important or ...understanding the pathophysiology of RA and selecting appropriate treatment for it, few studies have examined such single-nucleotide polymorphisms (SNPs) specifically in Japanese patients. This study was established to investigate the associations between polymorphisms in cytokine-encoding genes, autoantibodies and therapeutic responses in Japanese RA patients.
The subjects in this study consisted of 100 RA patients and 50 healthy controls. We extracted data on sex, age, disease duration, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and therapeutic responses, including to methotrexate (MTX) and biological disease-modifying antirheumatic drugs (DMARDs). Genomic DNA was isolated from peripheral blood, which was genotyped for IL-10, TNF-α, TGF-β
, and IFN-γ polymorphisms.
Regarding IL-10 (-592 C/A and -819 C/T), significant decreases in the frequencies of the IL-10 (-592) CC genotype and (-819) CC genotype were found in RA patients compared with the levels in controls. For IFN-γ (+874 T/A), a significant decrease in the frequency of the TT genotype was found in RA patients compared with that in controls. Regarding TGF-β
(+869 T/C), patients with positivity for anti-CCP antibody had a significantly lower frequency of the CC genotype than those with negativity for it. Furthermore, the IL-10 (-592) CC genotype and (-819) CC genotype might be related to the biological DMARD-response.
Our results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.
CD25 is an aberrant marker expressed on the leukemic stem cell (LSC) surface and an immunotherapy target in acute myeloid leukemia (AML). However, the clinical prevalence and significance of CD25 ...expression in pediatric AML are unknown. High IL2RA/CD25 expression in pediatric AML showed a stem cell‐like phenotype, and elevated CD25 expression was associated with lower overall survival (p < .001) and event‐free survival (p < .001) in the Japanese Pediatric Leukemia/Lymphoma Study Group AML‐05 study. This finding was reproduced in AML without a core‐binding factor in the Children's Oncology Group study cohort. High CD25 expression has prognostic significance in pediatric AML.
Abstract
Background
Whether optical frequency domain imaging (OFDI) images can realize pathological diagnosis of coronary atherosclerotic plaques, and whether its diagnostic accuracy of lesion types ...varies depending on the personal experience of the clinician caring for coronary intervention have not been elucidated.
Purpose
This study investigated the interobserver variability in characterizing atherosclerotic plaque types by OFDI for multiple OFDI observers with levels of different experience.
Methods
Three-hundred-thirty-three histological cross-sections from 21 autopsy hearts were co-registered with the corresponding OFDI images. Histological cross-sections were classified into the following 7 lesion types according to the modified AHA atherosclerosis classification by a single experienced pathologist blinded for OCT findings: adaptive intimal thickening (AIT), intimal xanthoma (IX), pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), calcified nodule (CN), and healed erosion/rupture (HER). The five OFDI observers, unaware of the histological diagnosis, provided a single diagnosis for each corresponding OFDI image. The OFDI observer 1 was an expert interventional cardiologist with sufficient experience in OFDI imaging, followed by the OFDI observer 2, 3, and 4 as middle career interventional cardiologists who had completed training ten, seven, and four years. The OFDI observer 5 was a young career interventional cardiologist. The diagnostic accuracy of lesion types for each OFDI observer was determined taking histology as a gold standard.
Results
On histological analysis, 13% of histological cross-sections were diagnosed as AIT, 5% as IX, 23% as PIT, 25% as FA, 27% as FC, 2% as CN, and 5% as HER. The overall agreement between OFDI diagnosis and histopathologic diagnosis for OFDI observer 1 to 5 was 77%, 62%, 61%, 56%, and 46% (k values of 0.71, 0.54, 0.54, 0.45, and 0.33), respectively. Although the performance for characterizing AIT and FC was excellent and comparable among all OFDI observers, the sensitivity and positive predictive value for characterizing IX, PIT and FA varied depending on the OFDI observers' years of experience (Table). The main causes of false-positive or -negative diagnosis of FA were IX and PIT for all OFDI observers.
Conclusion
The diagnostic accuracy of atherosclerotic tissue properties from OFDI images correlated with the observers' years of experience, subspecialty training in coronary imaging, which suggests that the interpretation of OFDI images requires expertise and can be challenging to a less experienced reader.
Table 1
Funding Acknowledgement
Type of funding source: None
The study was designed to determine the role of interferon (IFN)-gamma in inflammatory responses against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immunological ...responses in IFN-gamma gene knockout (IFN-gamma(-/-)) mice and immunocompetent control mice were compared. K. pneumoniae strain T-113 was inoculated intranasally into anaesthetised mice to induce pneumonia. Infected control mice survived significantly longer than infected IFN-gamma(-/-) mice. Viable bacterial counts in lungs and blood abruptly increased in IFN-gamma(-/-) mice; in contrast, a gradual decrease in the number of bacteria was noted in control mice. During the early stages of infection, the concentrations of interleukin (IL)-1beta and IL-6 in broncho-alveolar lavage fluid and IL-1beta in serum of IFN-gamma(-/-) mice were significantly lower than in control mice. During the late stage of infection, serum IL-6 level in IFN-gamma(-/-) mice was significantly higher than in control mice. These results suggest that the defective immunological host response, including inflammatory cytokine production caused by deficiency of IFN-gamma, is one of the mechanisms that allow the progression of pulmonary infection to systemic septicaemia.
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