Effect of gomisin A (TJN-101) on the arachidonic acid cascade in macrophages

It has been reported that leukotrienes (LTs) may play a role in inflammatory liver diseases, and several inhibitors of LTs show an inhibitory effect on experimental liver injuries. In this study, the effect of Gomisin A (TJN-101), which is a lignan component of schisandra fruits, on the arachidonic acid cascade in macrophages was examined to explain the mechanisms of the inhibitory effect of TJN-101 on liver injuries. The production of leukotriene B4 was suppressed by treatment with TJN-101, while the activity of 5-lipoxygenase was not affected. The release of arachidonic acid from macrophages stimulated with fMet-Leu-Phe or the Ca++ ionophore A23187 was suppressed by treatment with TJN-101. The activity of phospholipase A2 was not affected by treatment with TJN-101. These results suggested that TJN-101 produces an inhibitory effect on the biosynthesis of LTs by preventing the release of arachidonic acid, and it was thought that the preventive effect on the arachidonic acid cascade may be partially associated with the inhibitory effect of TJN-101 on liver injuries.     

Pseudo-adrenal incidentaloma: magnetic resonance imaging in a patient with para-adrenal Castleman's disease.

We report a case of para-adrenal angiofollicular lymph node hyperplasia (Castleman's disease) of the hyaline-vascular type. The mass could not be differentiated from an adrenal tumor by ultrasonography and computed axial tomography (CT). However, magnetic resonance imaging (MRI) suggested the possibility of an extra-adrenal origin of the mass. The intensity of the mass by MRI was homogeneous and of a higher intensity in the T2-weighted image than in the T1-weighted image, a finding similar to lymphadenopathy, lymphatic tumorous mass or metastatic tumor of the lymph node. Ultrasonography, CT and MRI may not be useful in characterizing Castleman's disease, but MRI was useful to distinguish asymptomatic para-adrenal masses from those of adrenal origin.     

CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration.

We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Eosinophilic fasciitis associated with Borrelia afzelii infection]

A 58-year-old woman suffered from stiffness, swelling, rubor and muscle pain in the extremities one month after she climbed a mountain in Kyushu, an island in southern Japan. On admission, mild proximal weakness was present in the extremities. Her range of motion in the extremities was limited due to firm skin and subcutaneous stiffness which was similar to scleroderma. She showed peripheral blood eosinophilia and hypergammaglobulinemia as well as a high erythrocyte sedimentation rate. An IgM antibody against Borrelia afzelii was positive. MRI of the skeletal muscles demonstrated enhancing fascia around the biceps brachii muscle, and a biopsy specimen revealed perivascular infiltration of mononuclear cells within the hypertrophic fascia. Eosinophilic infiltration was absent. We treated the patient with prednisolone, doxycycline and amoxicillin, which alleviated the symptoms. This is the first report to show that Borrelia afzelii was involved in eosinophilic fasciitis.     

Cerebellopontine angle ganglioneuroblastoma

Summary The CT, MR and histological features of a rare ganglioneuroblastoma of the cerebellopontine angle and cavernous sinus are reported.     

Case of Parkinson's disease presenting with unique dyspneic attacks caused by oromandibular dystonia and sleep apnea syndrome]

A 79-year-old woman with a 4-year history of Parkinson's disease was admitted due to unique dyspneic attacks with cyanosis while eating. Dyspneic attacks with cyanosis occurred mainly during actions such as taking meals or rehabilitation. Due to increased tonus of the orbicularis oris muscle, she was unable to open her mouth and breathe out, and finally experienced hypoxemia as revealed by pulse oxymetry. Dystonic hypertonus was relieved by touching the mandible with the fingers, and she was able to open her mouth again. These symptom was compatible with the sensory trick. Based on these findings, we considered that dyspneic attacks were produced by focal oromandibular dystonia. Polysomnography also showed central sleep apnea. We report herein a rare case of Parkinson's disease presenting with respiratory insufficiency caused by focal dystonia and central sleep apnea.