The effects of pentazocine, buprenorphine and butorphanol on human neutrophil functions.
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Biomedical subjects
Publications and source records attributed to H Akamatsu.
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BACKGROUND: Neutrophils play a crucial role in the antibacterial host defence system. Edaravone is used in critically ill patients who are often immuno-compromised secondary to concomitant disease or immunosuppressive therapy. The aim of the current study was to assess the effect of edaravone, a novel free-radical scavenger, on several aspects of human neutrophil function using an in vitro system. METHODS: Chemotaxis, phagocytosis, reactive oxygen species (ROS) production by neutrophil (cellular) and xanthine-xanthine oxidase (acellular) systems, and intracellular calcium ion levels ([Ca(2 +) ]i) were measured in the absence and in the presence (at a clinically relevant concentration, and 0.1-fold, and 10-fold this concentration) of edaravone. RESULTS: The clinically relevant concentration of edaravone did not inhibit chemotxais, phagocytosis, or superoxide production of neutrophils. Even at its ordinary clinical plasma concentration, the drug inhibited hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH*) generation in the cellular (neutrophil) as well as in the cell-free (xanthine-xanthine oxidase) system (P < 0.05). Edaravone did not affect elevation of [Ca(2 +) ]i in neutrophils stimulated by a chemotactic factor. CONCLUSIONS: These findings suggest that edaravone quenched H(2)O(2), and OH* generated rather than impaired the ability of neutrophils to produce the ROS. However, further studies using in vivo systems are required to elucidate the effects of edaravone on neutrophil function in clinical settings.
A 71-year-old male was admitted to the hospital complaining of cough. The chest X-ray and computed tomography (CT) revealed a large tumor in the right lower lung, which was diagnosed as poorly differentiated adenocarcinoma. As the tumor grew rapidly and caused obstructive pneumonia, right middle and lower lobectomy was performed even if right gingival tumor was suspected as metastasis from lung tumor. The patient complicated with aspiration pneumonia after operation and died on the 20th postoperative day. The prognosis of lung cancer with gingival metastasis is very poor. Early detection and appropriate therapy is necessary.
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BACKGROUND: Germline missense mutations in the GJB2 gene that encodes connexin-26 (Cx26) have recently been found to be the cause of the keratitis-ichthyosis-deafness (KID) syndrome. OBJECTIVES: To define the GJB2 mutations in three Japanese patients with KID syndrome. METHODS: Genomic DNA was extracted from peripheral blood and used to amplify the GJB2 gene. Direct sequencing and endonuclease digestion were used for mutation analysis and DNA-based diagnosis. RESULTS: We identified two heterozygous mis-sense mutations (D50Y, D50N) in the GJB2 gene in three Japanese patients with KID syndrome. All mutations were located on the first extracellular domain of Cx26. CONCLUSIONS: These data expand the GJB2 mutation database and show that a dominant mutation of Cx26 can cause KID syndrome in Japanese patients.
BACKGROUND: The incidence of atopic dermatitis (AD) has increased in Japan, along with the number of patients with severe and treatment-resistant AD in urban and industrial areas. We hypothesize that these changes could be due to increased reactive oxygen species (ROS) generated from environmental pollution and solar radiation. OBJECTIVES: To demonstrate whether direct oxidative protein damage of the stratum corneum of the biopsied skin from AD patients is increased when compared with controls. PATIENTS AND METHODS: Carbonyl moieties in skin biopsies from 75 patients with AD were assessed using both spectrophotometric and immunohistochemical detection of the formation of dinitrophenylhydrazone (DNP) from dinitrophenylhydrazine (DNPH). These were compared with diseased and normal controls. Lipid peroxidation was also assessed by staining with antibody to 4-hydroxy-2-nonenal (4-HNE), an aldehyde product of oxidized omega-6-fatty acids. In addition, the activity of superoxide dismutase (SOD), an effective scavenger of ROS, was assessed and compared with controls. RESULTS: The level of protein carbonyl moieties in patients' skin was elevated and correlated directly with the severity of the disease. In contrast, DNP formation was not significantly increased in diseased controls, when compared with healthy volunteers, and no statistical significance was found between the two control groups. SOD activity was increased except for those with extra-severe disease. Positive staining with anti-DNP antibody and anti-4-HNE antibody were found in the most superficial layers of the stratum corneum. CONCLUSIONS: This study has found an association between AD severity and markers of ROS-associated damage, adding weight to the hypothesis that environmentally generated ROS may induce oxidative protein damage in the stratum corneum, leading to the disruption of barrier function and exacerbation of AD.
Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging.
A 52-year-old female was admitted to the hospital because of increasing hemoptysis for twenty years. Chest computed tomography (CT) on admission showed bronchoectasia with dilated bronchial arteries in the left lower lung field. Bronchial arteriogram showed racemose hemangioma of bronchial arteries draining to left lower pulmonary arteries. Transresection of bronchial artery and partial lung resection was performed. The cut surface of the resected specimen showed bronchoectasia with dilated bronchial arteries (8 mm in diameter). She is well 15 months following the treatment with no evidence of hemoptysis.
A 21-year-old man developed an abnormal shadow of left hilum of the lung, discovered in an annual X-ray examination. The tumor grew 3 times in size as large as it had been 1 year before. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a homogenous mass lesion at the left interloblar portion of the left lung. CT revealed that the left pulmonary artery was markedly compressed by the tumor of left hilum. Surgical operation was performed under usual thoracotomy. The ligation of the branches of the left bronchial artery before tumor resection was very helpful to control bleeding from the tumor. We showed that a tumor of Castleman's disease may be resected without lobectomy of the lung or further procedures.
Staphylococcus aureus (S. aureus) often colonizes on the skin of patients with atopic dermatitis. It is known that superantigens which are staphylococcal enterotoxins can activate T cells without processing by antigen presenting cells. It has been suggested that activated T cells release various cytokines which may exacerbate or prolong the cutaneous inflammation associated with atopic dermatitis. Reduction of bacterial colonization from skin lesions has been reported to be effective in the treatment of atopic dermatitis. Therefore, antimicrobial therapy using antibiotics may be a treatment option for atopic dermatitis in selected patients. We examined the effect of antibiotics on the production of superantigen from S. aureus in vitro to determine the action mechanism of antibiotics in the treatment of atopic dermatitis. It was found that antibiotics with inhibitory effect on protein synthesis can suppress the production of superantigen. On the other hand, the superantigen production was not suppressed by antibiotics having either the inhibitory effect on cell wall synthesis or on nucleic acid synthesis. Levels of the suppressive effect on superantigen production by S. aureus varied with strains tested in this study. Moreover, we demonstrated that replication of DNA coding of superantigen produced by S. aureus was suppressed only by roxithromycin (ROX), which is a new macrolide. This finding suggests that ROX may have an effect at the gene level. These results suggested that the suppressive effects of antimicrobial agents that act as inhibitors of protein synthesis on superantigen production from S. aureus may be useful in the treatment of atopic dermatitis.
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BACKGROUND: The macrolide antibiotic roxithromycin is effective against acne associated with inflammation, but the mechanism by which this is achieved has not been clarified. OBJECTIVE: We studied the effects of roxithromycin on the production of lipase and neutrophil chemotactic factor by Propionibacterium acnes in vitro. RESULTS: Roxithromycin significantly inhibited the production of lipase and neutrophil chemotactic factor by P. acnes at a concentration one eighth of the MIC, at which the growth curve of P. acnes is not affected. CONCLUSION: One mechanism of the effectiveness of roxithromycin in acne therapy is thought to be the inhibition of bacterial lipase and neutrophil chemotactic factor production by P. acnes.
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A 71-year-old woman was admitted to our hospital with general fatigue and dyspnea. Emergency pacemaker implantation was performed after diagnosis of complete AV block. After 1 month, a small lung nodule, which had been 10 mm in diameter 1 year ago, was revealed to have grown to 15 mm in diameter by CT scan. Thoracoscopical resection of the lung nodule resulted in sarcoidosis. Abnormality in the posteroinferior heart was detected by 99mTC-PYP myocardial perfusion scintigraphy and it was diagnosed as cardiac sarcoidosis.
A 14-year-old male was admitted for complaints of dyspnea and cough. Chest radiography revealed a huge mass in the right lung field. The serum alpha fetoprotein (AFP) level was elevated to 1,251 ng/ml. Histological findings of the specimens obtained by needle biopsy revealed a mature teratoma with non-seminoma. After 2 courses of chemotherapy [cisplatin (CDDP) and etoposide (VP-16)], serum AFP level decreased to 25 ng/ml, and the tumor was resected with pericardium (the tumor size was 14 x 10 x 20 cm). Two courses of chemotherapy were administered again postoperatively with normalization of serum AFP level. The patient has no sign of recurrence of the tumor.
A 53-year-old male was admitted to the hospital because of progressive paralysis of inferior limb. Chest X-ray film and chest computed tomography (CT) on admission showed a small nodule with bullae in the right lower lung field. After CT-guided marking, partial lung resection including the nodule was performed. The cut surface of the resected specimen showed a tumor (10 mm in diameter) in a bullae measuring 14 mm in diameter. The tumor was diagnosed as amyloidosis. Fourty-six cases of primary localized pulmonary amyloidosis were reported in Japan. However, primary localized pulmonary amyloidosis with bullae is extremely rare, only 3 cases have been reported.
We demonstrated the immunoreactivity of the receptor proteins, VR1, ion channels associated with pain sensation, on the epidermis of the human skin. Immunohistochemistry using antiserum against VR1 derived peptide showed immunoreactivity on the keratinocytes cell membrane of the human epidermis and cultured keratinocytes. The blocking peptide of the antiserum reduced the immunoreactivity on the epidermis. RT-PCR assay of cultured human keratinocyte also showed expression of VR1 mRNA. These results suggest the existence of VR1-like protein in epidermal keratinocytes of human skin.