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Biomedical subjects

Junichi Chihara

Publications and source records attributed to Junichi Chihara.

32 records · Page 2Linked to original sources

[Hospital infection control reduced medical care costs by saving dispensable antibiotics].

Medical costs associated with hospital-acquired infection is a critical problem for hospital management. The introduction of the Diagnosis Procedure Combination (DPC) system requires the re-evaluation of the cost-effectiveness of any medical procedure including the usage of antibiotics. Achieving high cost-effectiveness and quality of medical service are essential for hospitals to survive the current changes in medical systems. Inappropriate use of antimicrobial agents results in unnecessary exposure to medication, persistent or progressive infection, emergence of resistance, and increased costs. We undertook an observational pre and post-intervention study to assess whether a comprehensive antimicrobial management program developed by the new ICT installed 2002 in Akita University Hospital could reduce the use of antibiotics. Annual total amounts of antibiotics and anti-MRSA antibiotics, and the number of patients undergoing long-term treatment with antibiotics, fell dramatically. This ICT approach thus reduced antibiotic costs, contributed to infection control, and improved the quality of antibiotic prescription.

Anti-Bacterial Agents↗

[Serum rheumatoid factor and peripheral blood eosinophil counts in patients with bronchial asthma].

These days some reports say that bronchial asthma, especially severe asthma, is systemic inflammatory and its severity correlates with eosinophil counts. Some patients with asthma have positive tests for rheumatoid factor (RF) which is detected in systemic hyper immunoreactive desease such as rheumatoid arthritis. So we investigated each of these factors in asthmatic patients. We randomly selected 100 asthmatics from regular outpatients of our hospital. In a positive RF level group (over 21 IU/ml), Eosinophil counts were significantly higher than those in a negative RF level group. RF levels were significantly and positively correlated with the logarithm of eosinophil count. And in severe groups (patients with severe asthma, treated with high dose inhaled steroids, and with history of systemic steroids use for the last one month), RF levels were significantly higher than those in other groups. Our result suggested that RF levels reflect eosinophilia and asthma severity.

Adolescent↗

Fecoflowmetric evaluation of anorectal function and ability to defecate in children with idiopathic chronic constipation.

Idiopathic chronic constipation (ICC) is one of the most common clinical conditions in children. The pathophysiology is multifactorial and differs from case to case. To investigate the relationship between anorectal motility (ARM) and clinical course in children with ICC, anorectal function was evaluated using fecoflowmetry in nine children aged 2-14 years (mean 6.1). Three were boys and six were girls. Pressure fluctuations in the rectum and anal canal were simultaneously recorded during saline (250-500 ml) infusion into the rectum. The dynamics of defecation were evaluated using recordings of the saline evacuation curve from the rectum in each patient. Seven patients showed periodic contractions of the rectum accompanied (five) or unaccompanied (two) by relaxations of the anal canal during saline infusion. These patients achieved comfortable spontaneous defecation during follow-up periods ranging from 5 to 20 months. The other two exhibited no rectal contractions in spite of relaxations of the anal canal, and did not respond well to long-term medical management. In eight patients segmental fecoflowmetric curves showed a significantly lower flow rate and longer evacuation time than those of controls. Fecoflowmetry is a simple and non-invasive technique for evaluation of the ability to defecate. Disturbances of ARM may play an important role in patients with severe ICC. When evaluating anorectal function in children with chronic constipation, more attention should be paid to ARM and fecodynamics.

Adolescent↗

Expression of PPARgamma in eosinophils and its functional role in survival and chemotaxis.

Eosinophils play a pivotal role in the mechanism of allergic diseases including asthma. Interleukin-5 (IL-5) and eotaxin are critical cytokines/chemokines for eosinophil activation. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates lipid metabolism. Recent evidence has suggested that PPARgamma serves as a negative regulator in the immune system. In the present study, we investigated the expression of PPARgamma and effect of PPARgamma agonist on human eosinophils. We demonstrated that purified eosinophils and Eol-1 cells express PPARgamma at the mRNA and protein levels. The PPARgamma agonist troglitazone reduced the IL-5-stimulated, but not spontaneous, eosinophil survival in a concentration-dependent manner. Moreover, the eotaxin-directed eosinophil chemotaxis was dose-dependently inhibited by troglitazone. Our results suggest that the administration of the PPARgamma agonists thiazolidinediones could be a new therapeutic modality for the treatment of allergic diseases such as asthma.

Apoptosis↗

Elevated serum levels of thioredoxin in patients with acute exacerbation of asthma.

The pathogenesis of bronchial asthma is chronic airway inflammation caused by immune cells such as T lymphocytes and eosinophils. Eosinophils release cytotoxic products including reactive oxygen species at the site of inflammation, leading to epithelial damage. Human thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced and secreted from cells by oxidative stress. This study was undertaken to investigate the clinical significance of TRX in the pathogenesis of asthma. We collected blood samples from 48 patients with bronchial asthma with or without attack, and measured serum ECP and pulmonary function as well as serum TRX. The serum TRX levels in patients with asthma were significantly increased in patients with mild (34.63 [28.40-42.73] ng/ml, medians with 25 and 75% interquartiles, P=0.0064) and moderate (38.83 [35.14-50.80] ng/ml, P=0.0017) asthma attacks compared with those during the asymptomatic period. The serum TRX levels were inversely correlated with FEV(1.0)% (r=-0.44, P=0.039) and %PEF (r=-0.49, P=0.020) during attack. There was a significant correlation between the serum TRX and the serum eosinophil cationic protein (rs=0.32, P=0.016). These findings suggest that serum TRX is related to the state of asthma exacerbation and allergic inflammation.

Asthma↗

Myosin light chain kinase mediates eosinophil chemotaxis in a mitogen-activated protein kinase-dependent manner.

BACKGROUND: Eosinophil migration in the tissue is one characteristic feature of allergic diseases. The CC chemokine eotaxin plays a pivotal role in local accumulation of eosinophils. Myosin light chain kinase (MLCK) is known to regulate cytoskeletal rearrangement and cell motility by means of phosphorylation of myosin light chain (MLC). OBJECTIVE: We have previously shown that mitogen-activated protein (MAP) kinases are important for eosinophil migration. In the present study we hypothesized that MLCK is downstream of MAP kinases, thereby linking the MAP kinase pathway to the activation of cytoskeletal components required for eosinophil chemotaxis. METHODS: Blood eosinophils were purified by using Percoll and anti-CD16 antibody-coated magnetic beads. We investigated the phosphorylation of MLCK and MLC by using the phosphorous 32-orthophosphates-labeled eosinophils. The kinase activity of MLCK was determined by measuring the phosphotransferase activity for the MLCK-specific peptide substrate. The chemotaxis assay was performed in a 48-well Boyden microchamber. RESULTS: The phosphotransferase activity of MLCK for a substrate peptide was enhanced in eotaxin-stimulated eosinophils. We also found that eotaxin induced phosphorylation of MLCK in vivo in phosphorous 32-orthophosphate-labeled eosinophils. PD98059 (MAP/extracellular signal-regulated kinase inhibitor) or SB202190 (p38 MAP kinase inhibitor) abrogated the eotaxin-induced phosphorylation of MLCK. The phosphorylation of MLC was upregulated by eotaxin. Eosinophil chemotaxis was inhibited by means of pretreatment of the MLCK inhibitor ML-7. CONCLUSION: These results suggest that eotaxin regulates MLCK through both extracellular signal-regulated kinase 1/2 and p38 MAP kinase. MLCK activation is a critical step in the cytoskeletal rearrangements leading to eosinophil migration.

Chemokine CCL11↗

Effect of ketotifen on the production of reactive oxygen species from human eosinophils primed by eotaxin.

Ketotifen is an antiallergic drug and may have direct inhibitory effects on eosinophils. To investigate the anti-eosinophilic effect of ketotifen, we examined the effect of ketotifen on the production of reactive oxygen species (ROS) from eotaxin-primed human eosinophils. Ketotifen at 10(-10)-10(-6) mol/l significantly reduced the production of ROS evoked by A23187 from eosinophils primed by eotaxin. In contrast, ketotifen at 10(-5) mol/l significantly augmented the production in the absence of eotaxin. We demonstrated that appropriate concentrations of ketotifen may have direct inhibitory effects on eosinophil oxidative metabolism primed by eotaxin. Ketotifen may contribute to the treatment of allergic disease through its anti-eosinophilic effects.

Anti-Allergic Agents↗

Evaluation of anorectal function in patients with tethered cord syndrome: saline enema test and fecoflowmetry.

OBJECT: Disturbance in anorectal function is a major factor restricting the activities of daily living in patients with spinal cord disorders. To detect changes in anorectal motilities due to a tethered spinal cord, anorectal functions were evaluated using a saline enema test and fecoflowmetry before and after patients underwent untethering surgery. METHODS: The bowel functions in five patients with a tethered cord syndrome (TCS) were evaluated by performing a saline enema test and fecoflowmetry. The contractile activity of the rectum, the volume of infused saline tolerated in the rectum, anal canal pressure, and the ability to evacuate rectal content were examined. The characteristic findings in anorectal motility studies conducted in patients with TCS were a hyperactive rectum, diminished rectal saline-retention ability, and diminished maximal flow in saline evacuation. A hyperactive rectum was considered to be a major contributing factor to fecal incontinence. In one asymptomatic patient diminished anal squeezing pressure was exhibited and was incontinent to liquid preoperatively, but recovered after surgery. Two patients who underwent surgery for myeloschisis as infants complained of progressive fecal incontinence when they became adolescents. In one patient fecal incontinence improved but in another patient no improvement was observed after untethering surgery. CONCLUSIONS: Fecodynamic studies allow the detection of neurogenic disturbances of the anorectum in symptomatic and also in asymptomatic patients with TCS. More attention should be paid to the anorectal functions of patients with TCS.

Anal Canal↗

Analysis of physical and laboratory findings in nontyphoidal salmonellosis.

Nontyphoidal salmonellosis has a wide variety of clinical presentations. With the aim of describing the detailed clinical presentations of gastroenteritis caused by nontyphoidal Salmonella spp., findings for 126 patients (1-94 years of age; 37.0 years on average) were analyzed. Nontyphoidal salmonellosis is prevalent from April to October in Akita, when the mean atmospheric temperature exceeds 10 degrees C. On physical examination, 3 patients had rebound tenderness and muscle guarding on their abdominal wall; 1 of these patients underwent surgery for associated acute appendicitis. Elderly patients tended to be more seriously affected, resulting in severe dehydration. Elevation of the serum C-reactive protein (CRP) level correlated well with a decline in the platelet count. Although nontyphoidal salmonellosis is a common cause of acute gastroenteritis, thorough investigation and meticulous care are required so that conditions requiring surgical treatment or those that are potentially fatal are not overlooked.

Adolescent↗

Evaluation of anorectal functions of children with anorectal malformations using fecoflowmetry.

BACKGROUND/PURPOSE: A simple and objective method evaluating the bowel functions of patients with anorectal anomalies is necessary. The authors applied fecoflowmetry and saline enama test for patients with anorectal anomalies to evaluate the fecodynamics and anorectal motilities in these children. METHODS: The bowel functions of 16 patients who underwent repair for anorectal malformations and 5 normal controls were evaluated by saline enema test and fecoflowmetry. The correlations between the clinical scores for the bowel functions and the parameters in fecodynamic studies were investigated. RESULTS: Seven of 16 patients exhibited periodical contractions of the rectum synchronized with relaxations of the anal canal during saline infusion as did the controls and had significantly higher clinical scores than the other patients. Two patients with severe chronic constipation lacked rectal contractions. Among the fecoflowmetric parameters, the maximum flow, average flow, and tolerable volume of saline infused into the rectum were significantly lower in the patients with low clinical scores than those of the controls. The maximal squeeze pressure and resting anal pressure were not significantly different between the patients and controls. CONCLUSION: Fecodynamic studies, such as fecoflowmetry and saline enema test, help in obtaining clinical indicators for the bowel functions of patients with anorectal anomalies.

Adolescent↗

The role of mitogen-activated protein kinases in eotaxin-induced cytokine production from bronchial epithelial cells.

Eotaxin is a critical chemokine eliciting migration of eosinophils and basophils in the pathogenesis of bronchial asthma. Recent studies have shown that the specific receptor for eotaxin, CCR3, is expressed in bronchial epithelial cells. Although mitogen-activated protein (MAP) kinases are involved in diverse cell functions of bronchial epithelial cells, their role in eotaxin signaling is unknown. In this study, we studied the activation and functional relevance of MAP kinases in bronchial epithelial cells stimulated with eotaxin. Eotaxin (1-100 nM) induced tyrosine/threonine phosphorylation and activation of extracellular regulated kinase (ERK) 1/2 and p38 in NCI-H(292) cells and normal human bronchial epithelial cells. The phosphorylation of these MAP kinases was detectable after 30 s, and peaked at 5 min. Eotaxin stimulated production of interleukin-8 and granulocyte macrophage colony-stimulating factor. Pretreatment of Compound X (a specific CCR3 antagonist), pertussis toxin, genistein, and wortmannin reduced the MAP kinase phosphorylation and cytokine production. The eotaxin-induced cytokine production was inhibited by specific inhibitors for MAP/ERK kinase (PD98059) and p38 MAP kinase (SB202190). These results suggest that both ERK1/2 and p38 MAP kinase activated by eotaxin have a critical role in the pathogenesis of asthma.

Bronchi↗

[Genetic diagnosis for inherited lung disorders].

Technological advances in molecular biology, as well as in genetic engineering, have created a revolutionary movement in both clinical and diagnostic methodologies. With progress in human genome analysis, the genes responsible for various diseases have been analyzed at a rapid pace. Research involving respiratory disease is no exception. Emphasis in this area has shifted from respiratory physiology to molecular biology. One example is cystic fibrosis(CF). However, CF is relatively rare in Japan. Furthermore, the search for universal genes that trigger bronchial asthma has not been successful. Genetic testing for respiratory disease has not been conducted as a component of general, routine clinical tests in Japan, due to the aforementioned reasons. Therefore, I would like to take this opportunity to introduce genetic respiratory diseases, the present state of genetic testing and prospects for the future.

Humans↗