α4 Nicotinic Acetylcholine Receptor Signaling Exacerbates Type 2 Airway Inflammation.
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Publications and source records attributed to Yoshiki Kobayashi.
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We evaluated the influence of collateral circulation on a donor left anterior descending artery and an appropriate cut-off value of coronary flow velocity reserve for the diagnosis of significant donor left anterior descending artery stenosis. Measurement of coronary flow velocity reserve by transthoracic Doppler echocardiography provides noninvasive assessment of significant left anterior descending artery stenosis. The cut-off value of coronary flow velocity reserve for the diagnosis of significant donor left anterior descending artery stenosis has not been well studied. We retrospectively examined 64 patients who had no significant left anterior descending artery stenosis and who had other coronary artery stenosis. Seventeen patients had collaterals from the left anterior descending artery (group A) and 47 patients did not have collaterals (group B). We prospectively examined 23 consecutive patients who had collaterals from the left anterior descending artery to other coronary arteries. Eight patients had a significant donor left anterior descending artery stenosis. Coronary flow velocity reserve assessment was performed by transthoracic Doppler echocardiography in the 2 protocols. Coronary flow velocity at baseline in group A was significantly higher than that in group B. Coronary flow velocity reserve in group A was significantly lower than that in group B (2.6 +/- 0.8 vs 3.2 +/- 0.9, p < 0.05). Coronary flow velocity during hyperemia and coronary flow velocity reserve were significantly lower in patients with significant stenosis. A cut-off value of 2.0 of coronary flow velocity reserve had a sensitivity of 88% and a specificity of 93% for the diagnosis of significant donor left anterior descending artery stenosis. In conclusion, coronary flow velocity reserve of a donor left anterior descending artery was decreased by the presence of collaterals. However, a cut-off value < 2.0 was appropriate for the diagnosis of significant donor left anterior descending artery stenosis in a population that included patients with collaterals.
Eosinophils are major effector cells in allergic diseases including asthma. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates immune reaction. We have previously demonstrated that human eosinophils express PPARgamma and that stimulation with a synthetic agonist for PPARgamma attenuated the factor-induced eosinophil survival and chemotaxis. However, the modulator of the eosinophil PPARgamma expression has not yet been studied. In this study, we investigated the effect of theophylline and dexamethasone (widely used drugs in the treatment of asthma) on PPARgamma expression in eosinophils. Purified human peripheral blood eosinophils were cultured, and therapeutic concentrations of theophylline and dexamethasone were added. Subsequently, PPARgamma was measured using quantitative real-time RT-PCR and flow cytometry. Theophylline and dexamethasone markedly enhanced both mRNA and protein levels of PPARgamma. These findings suggest that the increase in PPARgamma expression on eosinophils may play a role in the anti-inflammatory effects of theophylline and dexamethasone.
OBJECTIVE: Recently, elevated levels of plasma oxidized low-density lipoprotein (LDL) have been shown to relate to plaque instability in human atherosclerotic lesions. We investigated prospectively patients admitted with acute myocardial infarction (AMI) who underwent primary coronary stenting to evaluate whether the 6-month outcome could be predicted by measuring plasma oxidized LDL (ox-LDL) levels at the time of hospital discharge. METHODS AND RESULTS: Plasma ox-LDL levels were measured in 102 patients with AMI undergoing primary coronary stenting using a highly sensitive ELISA method. Measurements were taken on admission and at discharge, and the findings related to the clinical outcome. At 6-month follow-up, angiographic stent restenosis occurred in 25 (25%) of the 102 AMI patients. Plasma ox-LDL levels at discharge were significantly (P=0.0074) higher in the restenosis group than those in the no-restenosis group (1.03+/-0.65 versus 0.61+/-0.34 ng/5 microg LDL protein). Multiple regression analysis showed that only plasma ox-LDL levels at discharge were a statistically significant independent predictor for late lumen loss after stenting (beta=0.645; P<0.0001). CONCLUSIONS: This prospective study demonstrates that persistence of an increased level of plasma ox-LDL at discharge is a strong independent predictor of stent restenosis at 6-month follow-up in AMI patients.
There are very few reports of extensive and detailed cephalometric investigations of nonextraction treatment changes for patients with anterior open bite. The purpose of this study was to evaluate changes in dentomaxillofacial morphology by way of lateral and oblique cephalograms of patients who had undergone multiloop edgewise archwire (MEAW) therapy for anterior open-bite correction. The subjects consisted of 21 Japanese female patients who received MEAW therapy without premolar extraction. The mean pre- and posttreatment ages were 16 years 9 months and 19 years, respectively. Lateral and oblique cephalograms were taken before and after treatment. Fifteen angular and 29 linear measurements were obtained from the lateral cephalograms; 17 angular and 20 linear measurements were obtained from the oblique cephalograms. Treatment changes were evaluated by the paired t-test. The upward and forward rotational changes of the mandible consequent to the use of the MEAWs and anterior vertical elastics were larger than the downward and backward rotational changes of the mandible, due to the extrusion of the posterior teeth by leveling and alignment. The uprighting and retrusion of the premolars and molars, and the extrusion, uprighting, and/or retrusion of the incisors and canines played important roles in the anterior open-bite nonextraction treatment by dint of the MEAW technique.
BACKGROUND: According to recent intravascular ultrasound (IVUS) studies, expansive remodeling (ER) at the culprit lesion has been observed in almost 50% of patients with acute coronary syndrome and constrictive remodeling (CR) in 30%. The purpose of this study is to investigate the difference between ER and CR at the culprit lesion in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Preinterventional IVUS images of 73 patients with AMI were identified. The remodeling index (RI) was defined as the ratio of the external elastic membrane (EEM) areas at the culprit lesion to the EEM areas at the proximal reference site. Expansive remodeling was defined as an RI > 1.05; CR, as an RI < 0.95. In patients with AMI, 40 patients (55%) showed ER on IVUS, whereas CR was observed in 18 patients (25%). Patients with ER were significantly older than those with CR (P < .005). The frequency of the presence of calcifications was higher in patients with ER than in those with CR (P < .0005). In patients with AMI with ER, soft plaque with small calcium was the most frequent (58%). Multivariate analysis revealed that age and the presence of calcifications remained as independent predictors of ER. CONCLUSIONS: These findings suggest that ER relates to old age and calcification, and CR may contribute to early plaque progression than ER in patients with AMI.
The relationship between the blood level of rheumatoid factor (RF) and the peripheral blood eosinophil (Eo) count (white blood cellsx%Eo, Eo count) in a patient diagnosed with chronic eosinophilic pneumonia was evaluated from before the onset till resolution of the disease. RF levels correlated with Eo counts, and showed a strong correlation with the logarithmic value of the Eo counts (r=0.816). RF levels tended to become elevated earlier and decline later than Eo counts or abnormal X-ray shadows. We concluded that the RF level may reflect the activity of this disease. The mechanism of RF elevation in eosinophil-activated disorders needs to be clarified.
This study determined the physical fitness component that contributes to improving and maintaining health status for each age group as well as quantifying the degree of the relationship between health status and physical fitness in middle-aged and elderly males. The participants were 995 males aged 30 to 69 years. Ten physical fitness tests and medical checkups were performed. The participants were divided into a healthy group and an unhealthy group according to health status. Multiple discriminant analysis was applied to the multivariate data. Correct discriminant probabilities of the multiple discriminant function to discriminate the healthy and unhealthy groups for males ranged from 67.0% to 75.1%. These findings suggest that there is a relatively high relationship between the health status and physical fitness level for middle-aged and elderly males. With each individual's discriminant score calculated using the multiple discriminant function as the index of the degree of health, the Pearson's correlation coefficient of the discriminant score and the performance in each physical fitness test were calculated. The age change between 30 and 69 years old was classified into five patterns according to the contribution. The result of this study is considered to be useful as objective data to prepare an exercise program considering the contribution of the physical fitness component of health status.
Calcification is a common finding in human coronary arteries. However, there is conflicting evidence for a link between calcification and plaque instability. Current intravascular ultrasound (IVUS) technology allows a definitive detection of the calcification and measurement of the vessel wall. Using preinterventional IVUS images, we clarified that in patients with acute myocardial infarction, small "spotty" calcifications prevailed, associated with a fibrofatty plaque and positive remodeling. Conversely, in patients with stable angina pectoris, extensive calcification was frequent. IVUS allows the detection of vulnerable plaques in coronary arteries, by identifying not only a large lipid core and positive remodeling, but also a spotty pattern of calcification.
OBJECTIVES: Optical coherence tomography(OCT)is a high-resolution imaging method that can clearly visualize vessels through the displacement of blood with flushing agents. Continuous imaging methods have not been established. This study investigated optimal methods for continuous OCT imaging. METHODS: Thirty-four arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14 pigs were examined using OCT with a motorized pullback device. Two imaging methods (flush alone by liquid substance and flush with occlusion) were compared. Adequate image acquisition was defined as the entire circumferential intimal layer being detectable within continuous segments. To investigate factors that could influence image quality, stented regions were divided into 4-5 mm segments. RESULTS: The flush with occlusion method provided better OCT images compared to flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using the flush with occlusion method, the rate of adequate image acquisition was 64.4% and visualization of > 75% intimal circumference was 83.5%. Intravascular ultrasound could detect all stented regions. Segmental analyses found more adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4 mm, inadequate segment: 4.2 +/- 0.8 mm, p < 0.0001) or with centered image wire position (adequate segment: center 35%, inadequate segment: center 14%, p = 0.003). In addition, side branches did not affect image quality. CONCLUSIONS: To acquire continuous OCT images, the flush with occlusion method was more effective compared to flush alone. Moreover, image quality is affected by vessel size and imaging wire position. These results suggest that optimized OCT imaging can provide continuous vessel detection.
Here we report two cases of congenital myopathy visited our hospital with respiratory failure. Case 1 was a 31-year-old woman, who had muscular weakness from birth but had never been diagnosed. She had an onset of pneumonia followed by severe type 2 respiratory failure. Even after the healing of pneumonia, hypercapnia remained. A diagnosis of nemaline myopathy was made after muscle biopsy. Case 2 is a 62-year-old man, who had slowly progressing respiratory failure accompanied with severe hypercapnea. His respiratory failure was improved by NIPPV. He also under went muscle biopsy and nemaline myopathy was diagnosed. Nemaline myopathy is one of congenital myopathy and is known to be a nonprogressive or slowly progressive disorder. However, some patients are diagnosed appropriately only when adult onset acute respiratory failure occurs.
15-Deoxy-Delta12,14-PGJ2 (15d-PGJ2), mainly produced by mast cells, is known as a potent lipid mediator derived from PGD2 in vivo. 15d-PGJ2 was thought to exert its effects on cells exclusively through peroxisome proliferator-activated receptor-gamma (PPARgamma) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), which are both expressed on human eosinophils. However, the physiological role of 15d-PGJ2 remains unclear, because the concentration generated in vivo is generally much lower than that required for its biological functions. In the present study we found that low concentrations (picomolar to low nanomolar) of 15d-PGJ2 and a synthetic PPARgamma agonist markedly enhanced the eosinophil chemotaxis toward eotaxin, and the effect was decreased in a dose-dependent manner. Moreover, at a low concentration (10(-10) M), 15d-PGJ2 and troglitazone primed eotaxin-induced shape change and actin polymerization. These priming effects were completely reversed by a specific PPARgamma antagonist, but were not mimicked by CRTH2 agonist 13,14-dihydro-15-keto-PGD2, suggesting that the effects were mediated through PPARgamma ligation. The effect exerted by 15d-PGJ2 parallels the enhancement of Ca2+ influx, but is not associated with the ERK, p38 MAPK, and NF-kappaB pathways. Furthermore, the time course and treatment of eosinophils with actinomycin D, an inhibitor of gene transcription, indicated that the transcription-independent pathway had a role in this process. PPARgamma might interact with an eotaxin-induced cytosolic signaling pathway, because PPARgamma is located in the eosinophil cytosol. Taken together with current findings, these results suggest that under physiological conditions, 15d-PGJ2 contributes to allergic inflammation through PPARgamma, which plays a role as a biphasic regulator of immune response.
BACKGROUND: C-C chemokines and adhesion molecules expressed on eosinophils play an important role in the pathology of allergic inflammatory disease. C-C chemokines such as eotaxin or RANTES are involved in beta(2) integrin expression on purified eosinophils; so far we have no data on unpurified eosinophils in the peripheral blood. We measured beta(1) and beta(2) integrin activation after stimulation with eotaxin or RANTES in vitro using whole-blood flow-cytometric analysis. METHODS: Heparinized whole blood obtained from allergic patients with eosinophilia or normal subjects was diluted with the same volume of RPMI 1640, and then cells were incubated in the presence or absence of PMA/ionomycin or chemokines for 45 min at 37 degrees C. After hemolyzation with lysing solution, expression of CD11b, CD11a, CD18 and CD49d on eosinophils was measured using flow cytometry. RESULTS: The expression of CD11b, CD11a and CD18 in allergic patients was significantly higher than that in normal subjects. CD11b and CD18 expression showed a significant increase after stimulation with C-C chemokines, which was remarkable in allergic patients. CONCLUSION: Eosinophils in the blood of allergic patients exhibited a higher expression of beta(2) integrins and were more sensitive to RANTES and eotaxin than those of normal subjects.
Infection Control Committee (ICC) of Akita University Hospital was established in 1980's, when methicillin-resistant Staphylococcus aureus (MRSA) spread in teaching hospitals in Japan. After 20 years from the establishment of ICC, we needed to shake up some of the outdated infection control systems. Infection Control Team (ICT) was established in 2002 to reinforce ICC. ICT was consisted of five infection control doctors (ICD), two infection control nurses (ICN), two medical technicians in bacteriological division of clinical laboratory, one pharmacist and three administrative officials in the hospital. Monitoring of multiple drug-resistant pathogens, antibiotic use, surgical site infections and bloodstream infections are mandatory. Personnel training and educational activity are also required. After the establishment of ICT, inappropriate use of antibiotics and prevalence of MRSA were dramatically decreased. The hospital saved more than 30,000,000 yen annually. However, with a great regret, we experienced an outbreak of MRSA in a department of our hospital in 2003. MRSA infection was judged as a cause of death in three patients in the outbreak. MRSA was thought to transmit via medical personnel since pulsed-field gel electrophoresis revealed common genotype in 11 out of 15 patients studied. Prevention of healthcare-associated infections is a crucial in the management of hospitals. In this paper, we verified the efforts to control the outbreak and analyzed factors interfering infection control activities. A crucial role of a clinical laboratory in controlling healthcare associated infections was also discussed.
A 52-year-old man was given a diagnosis of type 2 diabetes mellitus at age 39. At age 46, he stopped taking medication. Two weeks after burning his legs at low temperature, he fell, using his right arm to protect his legs. The next day, he complained of pain and slight swelling from his right shoulder to his anterior chest and came to our hospital. At that time, a plain computed tomography scan suggested gasogenic bacterial infection and we discussed the indications for debridment. Although his widespread inflammation required extensive treatment including thoracostomy, we abandoned surgical treatment and administered several antibiotics in appropriate combination because of his severe condition. After admission, the mass grew rapidly and it was diagnosed as necrotizing fasciitis based on percutaneous needle biopsy and clinical findings. Although both inflammatory reactions and mass size tended to improve, he had repeated recurrence of pain and swelling in his right anterior chest. When he had a second recurrence, he received additional short-term steroid therapy. Afterwards he had no further recurrence. In this case, early clinical diagnosis, using broad-spectrum antibiotics prior to definite diagnosis, and additional short-term steroid therapy at the time of the recurrence were effective.
BACKGROUND: Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented. METHODS AND RESULTS: Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90 degrees for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of <90 degrees per patient was significantly higher in AMI than in SAP (P<0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8). Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001; mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification. CONCLUSIONS: Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcification.
This study evaluated the effects of the temporary occlusion and aspiration device GuardWire on percutaneous coronary intervention for acute myocardial infarction. This device brought about a significant reduction in the no-reflow phenomenon and improvement in ST resolution compared with conventional percutaneous coronary intervention.
BACKGROUND: In a previous study the adjusted thresholds at which the diameters of coronary arteries determined by enhanced electron-beam computed tomography (CT) scans are equal to the corresponding quantitative coronary angiography measurements were analyzed, and their correlation with maximum CT values for the vessel short axes was determined. A rapid accurate method for such measurements was sought by substituting maximum CT values for the descending aorta in the corresponding axial images for those for the short axes. METHODS AND RESULTS: In 8 patients, 179 sites were measured. Means (+/- SD) of adjusted thresholds and the maximum CT values for vessel short axes and the descending aorta in the corresponding axial images for all vessels were 108 +/-66, 227+/-80, and 363+/-75 Hounsfield Unit (HU), respectively. Adjusted thresholds correlated with the maximum CT values for the corresponding vessel short axes and the descending aorta in the corresponding axial images, with R2=0.55, 0.33, p<0.01, respectively. An abbreviated formula for use of maximum CT values for the descending aorta in the corresponding axial images was y=0.5x-75 (HU) (y= adjusted threshold, x= maximum CT value for the descending aorta in the corresponding axial image). CONCLUSIONS: The abbreviated formula provided a rapid, accurate method for measurements independent of arterial enhancement.