Selective phosphodiesterase type 4 inhibitors reduce the prolonged survival of eosinophils stimulated by granulocyte-macrophage colony-stimulating factor

It is well known that bronchial asthma is defined as chronic eosinophilic inflammation of the respiratory tract and that as one of the various types of inflammatory cells, eosinophils induce the airway inflammation of chronic asthma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the prolongation of the survival of eosinophils. We investigated the inhibitory effect of the selective phosphodiesterase (PDE) 4 inhibitors, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]purin-5-one (XT-611) and rolipram, and the nonselective PDE inhibitor theophylline, against GM-CSF-induced prolongation of the survival of eosinophils isolated from patients with bronchial asthma. Eosinophils (10(6) cells/ml) were incubated in the presence of GM-CSF together with or without theophylline, rolipram or XT-611 at 37 degrees C, and the viable cells were assessed up to 4d using Trypan blue dye exclusion. The presence of theophylline (10(-4) M), rolipram (10(-4)-10(-5) M) or XT-611 (10(-4)-10(-5) M) significantly reduced the GM-CSF (10 pg/ml)-induced prolongation of viability of eosinophils. These findings suggest that selective PDE 4 inhibitors, including XT-611, may effectively reduce the activities of inflammatory cells in the airway of bronchial asthma patients.     

Early-enhancing nonneoplastic lesions on gadolinium-enhanced magnetic resonance imaging of the liver following partial hepatectomy

PURPOSE: To assess the frequency, imaging findings, and significance of early-enhancing nonneoplastic (EN) lesions with gadolinium-enhanced magnetic resonance imaging (MRI) of the liver following partial hepatectomy. MATERIALS AND METHODS: We retrospectively reviewed MR images after partial hepatectomy in 30 patients. Postoperative MRI was performed in 1-12 months (mean, 3.7 months) after partial hepatectomy. We defined the EN lesion as a lesion that was ill defined; irregular, wedge shaped, or serpiginous; located along the liver edge; not visible on unenhanced MR images; did not appear hypointense on portal venous- or equilibrium-phase images; or a combination of those imaging findings. RESULTS: A total of 39 EN lesions (size range, 5-60 mm; mean, 25.2 mm) in 19 patients and 17 recurrent tumors (size range, 5-50 mm; mean, 16.8 mm) in 10 patients newly appeared after partial hepatectomy. The EN lesions were diagnosed as pseudolesions by the second postoperative follow-up MRI in 17 patients or contrast-enhanced computed tomography (CT) in two. A total of 13 EN lesions (33%) were located along the liver edge and 20 (51%) were adjacent to the resected area. The shape was circular in 11 (28%), oval in three (8%), irregular in 11 (28%), wedge shaped in five (13%), and serpiginous in nine (23%). No EN lesion showed hypointensity on gadolinium-enhanced portal venous-phase or equilibrium-phase images. A total of 14 EN lesions (36%) showed slight hyperintensity on T2-weighted images. The confidence levels for malignancy probability assigned by blinded radiologists were lower with EN lesions than with recurrent tumors (P < 0.001). CONCLUSION: EN lesions are frequently seen in MRI following partial hepatectomy, and occasionally are slightly hyperintense on T2-weighted images, mimicking malignant tumors. However, most EN lesions can be correctly diagnosed with MRI findings.     

Mitogenic activity of gelatin to murine spleen cells

We reported previously that gelatin stimulates the growth of spleen cells in vitro. Tritium thymidine (3H-TdR) uptake into phytohemagglutinin (PHA)-stimulated spleen cells as well as intact spleen cells was augmented by gelatin. These findings suggest that gelatin serves as a mitogen for lymphoid cells. In this study, the target of action of gelatin was investigated. Tritium thymidine uptake into T cell-rich fraction was enhanced by incubation with 7.5 mg/ml of gelatin for 48 hours. The level of 3H-TdR uptake into B cell-rich fraction was not definitely increased by gelatin. Flow cytometric analysis confirmed these findings. Namely, it showed that treatment of spleen cells with 7.5 mg/ml gelatin increased a ratio of CD3-positive cells and decreased that of CD19-positive cells. Tritium thymidine uptake into natural killer cell-rich fraction was augmented by gelatin in a similar fashion to T cell-rich fraction. Tritium thymidine uptake into macrophages was very low and not affected by gelatin. Tritium thymidine uptake into macrophage-precursors was very low but was enhanced by gelatin. These findings suggest that gelatin could be used as an agent of cancer biotherapy.     

A discussion of anti-Aspergillus niger glucose oxidase monoclonal antibody reactivity to red blood cells of several species

We observed that mouse spleen cells from rosettes with autologous red blood cells (RBCs) and that rosette-formation was suppressed by anti-Aspergillus niger glucose oxidase monoclonal antibody (mAb). In the present study, we investigated whether RBCs of species besides mice have the structure recognized by anti-A. niger glucose oxidase mAb by using rosette-formation and complement-mediated hemolysis. Lysates of monkey and human RBCs did not suppress rosette-formation whereas autologous (mouse), rat and sheep RBC lysates partially suppressed rosette-formation. Those lysates exerted their suppressive activity after they had been treated at 56 degrees C for 30 min. A. niger glucose oxidase also suppressed rosette-formation with or without treatment at 56 degrees C for 30 min. Alternatively, anti-A. niger glucose oxidase mAb lysed mouse, rat and sheep RBCs but not human RBCs with complement. These findings suggest that the cell surfaces of mouse, rat and sheep RBCs have a structure which can be recognized by anti-A. niger glucose oxidase mAb while the cell surfaces of monkey and human RBCs do not.     

Clinical outcome of Epstein–Barr virus‐positive diffuse large B‐cell lymphoma of the elderly in the rituximab era

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. The incidence of Epstein–Barr virus (EBV)‐positive DLBCL in Asian and Latin American countries ranges from 8 to 10%. The prognosis of patients with EBV‐positive DLBCL is controversial. To compare the clinical outcome of EBV‐positive and EBV‐negative patients with DLBCL in the rituximab era, we analyzed 239 patients with de novo DLBCL diagnosed between January 2007 and December 2011. The presence of EBV in lymphoma cells was detected using EBV‐encoded RNA in situ hybridization, and it was found that 18 (6.9%) of 260 patients with diagnosed DLBCL tested positive. Among the 260 cases, 216 cases were treated with rituximab plus chemotherapy, as were 8 EBV‐positive DLBCL patients. The median overall survival and progression‐free survival times in patients with EBV‐positive DLBCL were 8.7 months and 6.8 months, respectively. The median overall survival and progression‐free survival could not be determined in EBV‐negative DLBCL patients (P = 0.0002, P < 0.0001, respectively). The outcome of patients with EBV‐positive DLBCL remains poor, even in the rituximab era.     

A surgically treated case of ileus caused by small intestinal tuberculosis during treatment for pulmonary tuberculosis

A 44-year-old man consulted medical clinic, complaining of cough and sputum. Then he was admitted to our hospital, because of positive acid-fast bacilli in his sputum and positive PCR (polymerase chain reaction) for Mycobacterium tuberculosis. Combined use of isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA) was started. But 4 days after starting treatment, we had to suspend tuberculosis chemotherapy because of hepatopathy. Since then he started to complain epigastralgia and vomiting. Plain abdominal X-ray and abdominal computed tomography (CT) led to a diagnosis of ileus. Inspite of insertion of ileus tube symptoms of ileus did not improve. Small bowl series showed severe stenosis at ileum end, necessitating jejunectomy. Macroscopic study revealed a ring ulcer and multiple epithelioid cell granuloma with Langhans' giant cells was detected histopathologically. PCR for M. tuberculosis of extracts from ileum was positive. Therefore the patient was diagnosed small intestinal tuberculosis. Treatment was continued by the combination of INH, RFP, EB, and the symptoms markedly improved. There have been no sign of recurrence since the end of the 6-month treatment for tuberculosis.