A peptide against the N-terminus of myristoylated alanine-rich C kinase substrate inhibits degranulation of human leukocytes in vitro.

Leukocytes synthesize a variety of inflammatory mediators that are packaged and stored in the cytoplasm within membrane-bound granules. Upon stimulation, the cells secrete the granule contents via an exocytotic process whereby the granules translocate to the cell periphery, the granule membranes fuse with the plasma membrane, and the granule contents are released extracellularly. We have reported previously that another exocytotic process, release of mucin by secretory cells of the airway epithelium, is regulated by the myristoylated alanine-rich C kinase substrate (MARCKS) (Li Y, Martin LD, Spizz G, Adler KB. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. J Biol Chem 2001;276:40982-40990; Singer M, Martin LD, Vargaftig BB, Park J, Gruber AD, Li Y, Adler KB. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat Med 2004;10:193-196). In those studies, mucin secretion in vitro and in vivo was attenuated by a synthetic peptide identical to the N-terminus of MARCKS, named the MANS peptide (Li and colleagues, 2001). In this study, we used the MANS peptide to investigate possible involvement of MARCKS in secretion of leukocyte granule proteins. In neutrophils isolated from human blood, phorbol 12-myristate 13-acetate-induced myeloperoxidase release was attenuated in a concentration-dependent manner by MANS but not by equal concentrations of a missense control peptide. In additional studies using human leukocyte cell lines, secretion of eosinophil peroxidase from the eosinophil-like cell line HL-60 clone 15, lysozyme from the monocytic leukemia cell line U937, and granzyme from the lymphocyte natural killer cell line NK-92 were attenuated by preincubation of the cells with MANS but not with the missense control peptide. The results indicate that MARCKS protein may play an important role in the secretion of membrane-bound granules from different leukocytes. MARCKS may be an important component of secretory pathways associated with release of granules by different cell types.

[Four cases of Klebsiella pneumonia].

Typical Klebsiella pneumonia with mucous sputum is known as an opportunistic nosocomial infection. However, computed tomographic study of limiting in Klebsiella pneumonia is rare. We report three types of chest computed tomography (CT) findings for Klebsiella pneumonia. Case 1 shows typical lobar pneumonia (Friedlander pneumonia), Cases 2 and 3 show acute bronchopneumonia with subclinical aspiration, and Case 4, chronic Klebsiella pneumonia with typical cavitary lung abscesses. Of these four cases of Klebsiella pneumonia, three developed in the right lung, as determined radiologically, but esophagogastroduodenoscopy indicated that the lesions of Case 3 had developed in the left lingula and upper lobe.

Small-intestinal sarcomatoid carcinoma with superior vena cava syndrome.

A 56-year-old man was hospitalized because of swelling of the right upper extremity and anemia. A diagnosis of superior vena cava (SVC) syndrome caused by lymphogenous metastasis was made after chest computed tomography (CT) scan and biopsy of cervical lymph nodes were carried out. Standard examinations, such as abdominal CT scan and endoscopies of the upper and lower gastrointestinal tract, failed to find the primary lesion. However, selective angiography of the superior mesenteric artery (SMA) showed a clear stain of bleeding vessels in the small intestine. Laparotomy was performed, and immunohistochemical findings revealed sarcomatoid carcinoma in the small intestine (a rarely seen neoplasm). This aggressive carcinoma, which showed negative reactivity with CD34, CD117 (c-kit), and S-100 was clearly distinguished from other mesenchymal tumors, such as malignant gastrointestinal stromal tumor (GIST) and malignant fibrous histiocytoma (MFH).

Histamine and serotonin stimulate eotaxin production by a human lung fibroblast cell line.

Histamine and serotonin are important inflammatory mediators in the pathophysiology of asthma, and asthmatic patients have higher plasma histamine and serotonin levels than nonasthmatic control subjects. Eotaxin, a potent eosinophil-specific chemotactic factor, is increased in the lower respiratory tract of allergic patients. Recently, lung fibroblasts have been reported to produce eotaxin and are suggested to be the major cellular source of eotaxin. We postulated that lung fibroblasts might release eotaxin in response to histamine or serotonin. To test this hypothesis, we evaluated the potential of histamine or serotonin to induce the release of eotaxin by the human fetal lung fibroblast cell line, HFL-1. HFL-1 released eotaxin in response to histamine and serotonin in a dose- and time-dependent manner (p < 0.05). Histamine or serotonin treatment of HFL-1 augmented the expression of eotaxin mRNA. Eosinophil chemotactic activity by HFL-1 supernatant fluids was inhibited by anti-human eotaxin-neutralizing antibody. These findings lead to the hypothesis that lung-fibroblast-derived eotaxin may in part be responsible for the eosinophil infiltration observed in allergic disease of the airways.

[An infection with Legionella pneumophila treated with intravenous ciprofloxacin].

A 60-year-old diabetic man who had had a coronary artery bypass graft operation was admitted to Okaya Enrei Hospital because of coughing, high fever and dyspnea. Chest high-resolution computed tomography scans revealed bilateral pleural effusions and left-sided alveolar shadows and ground glass opacity. These infiltrations in the left lung field showed rapid growth. Legionella pneumonia was diagnosed because of a high titer for Legionella pneumophila antigen in the urine. He was treated with 600 mg per day of parenteral ciprofloxacin for two weeks and 10 mg per day of oral prednisolone for the second week, resulting in improvement of the clinical findings.