Miki Nishikawa

Clarithromycin Inhibits NF-κB Activation in Human Peripheral Blood Mononuclear Cells and Pulmonary Epithelial Cells

ABSTRACT Macrolide antibiotics modulate the production of proinflammatory cytokines in vivo and in vitro. Transcription of the genes for these proinflammatory cytokines is regulated by nuclear factor κB (NF-κB). We examined whether or not clarithromycin inhibits the activation of NF-κB induced by tumor necrosis factor alpha (TNF-α) or staphylococcal enterotoxin A (SEA) in human monocytic U-937 cells, a T-cell line (Jurkat), a pulmonary epithelial cell line (A549), and peripheral blood mononuclear cells (PBMC). Flow cytometry revealed that clarithromycin suppresses NF-κB activation induced by TNF-α in U-937 and Jurkat cells in a concentration-related manner. Western blot analysis also demonstrated that clarithromycin inhibits NF-κB activation induced by TNF-α in U-937, Jurkat, and A549 cells and PBMC and by SEA in PBMC. Western blot analysis of cytoplasmic extracts of A549 cells revealed that this inhibition is not linked to preservation of expression of the IκBα protein. The chloramphenicol acetyltransferase assay indicated that NF-κB-dependent reporter gene expression is suppressed in U-937 cells pretreated with clarithromycin. These findings are consistent with the idea that clarithromycin suppresses the production of proinflammatory cytokines via inhibition of NF-κB activation.

Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis

Three children ranging in age from 2 to 5 years with acute disseminated encephalomyelitis (ADEM) were successfully treated with high-dose intravenous immunoglobulin (IVIG). Their symptoms were somnolence, fever, headache, vomiting, and resting tremor. In all of these patients, it was difficult to distinguish the condition from viral encephalitis before analyzing the myelin basic protein. ADEM was diagnosed because of increased levels of myelin basic protein in their cerebrospinal fluid and abnormal high-signal intensity on T2-weighted magnetic resonance imaging. All patients were given IVIG at a dose of 400 mg/kg/day for 5 consecutive days. The patients rapidly regained consciousness in 14 hours, 2 days, and 4 days and demonstrated a complete clinical improvement within 18 days, 10 days, and 7 days of the initiation of the treatment, respectively. IVIG may prove useful as an alternative treatment to corticosteroids for ADEM.

Cerebral Hypoperfusion During Acute Kawasaki Disease

BACKGROUND AND PURPOSE Kawasaki disease is a febrile disease of children notable for systemic vasculitis. There have been many previous reports of various complications, including disorders of the central nervous system. We evaluated cerebral perfusion during the acute stage in patients with Kawasaki disease. METHODS Single-photon emission-computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime was performed in 21 children with acute stage Kawasaki disease. Follow-up SPECT and MRI were performed about 1 month after the first SPECT in patients who exhibited abnormal SPECT findings during the acute stage. RESULTS In 6 of 21 children SPECT imaging demonstrated localized cerebral hypoperfusion without abnormal neurological findings or clinical symptoms, and the follow-up SPECT and MRI approximately 1 month after the first SPECT revealed no abnormalities. CONCLUSIONS Some patients with Kawasaki disease have transient localized cerebral hypoperfusion at the acute stage.

Mononuclear cells and cytokines in the cerebrospinal fluid of echovirus 30 meningitis patients.

The local immune response to echovirus 30 meningitis in children was investigated in 2 ways: using flow cytometry to examine the mononuclear cell and lymphocyte subsets and enzyme-linked immunosorbent assays to examine the cerebrospinal fluid (CSF) levels of cytokines, including monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-gamma) and interleukin-12 (IL-12). The numbers of macrophages in the CSF were increased, in particular during the early part of the acute stage. The levels of MCP-1, which is responsible for the accumulation of macrophages, as well as those of IFN-gamma and IL-12, which play important roles in the activation of macrophages and T helper (Th) 1 cells, respectively, were increased in the CSF of patients compared with the levels found in the controls. Likewise, numbers of activated CD4 + and CD8 + T lymphocytes were increased in the CSF. Since the ratio of CD4/CD8 correlated with the age of the patients, CD8 + T lymphocytes in the CSF might play a more important role in younger children.

NF-κB activation in cerebrospinal fluid cells from patients with meningitis

Abstract We examined whether or not NF-κB, a factor that regulates expression of the genes that code for pro-inflammatory cytokines, is activated in cerebrospinal fluid (CSF) cells to investigate the production of pro-inflammatory cytokines by CSF cells in patients with meningitis. Western blotting demonstrated that NF-κB was more activated in CSF cells of patients with bacterial meningitis than in those of patients with aseptic meningitis. NF-κB was hardly activated in carcinomatous meningitis. The NF-κB activation in CSF cells of patients with meningitis tended to be correlated with the CSF interleukin-6 concentration. Our data suggested that CSF cells produce pro-inflammatory cytokines through NF-κB activation in meningitis, and that increased NF-κB activation in CSF cells indicate infectious meningitis rather than carcinomatous meningitis.

Cerebrospinal fluid levels of soluble tumour necrosis factor receptor in acute encephalitis

Soluble tumour necrosis factor receptor (sTNF-R) inhibits the action of TNF-α. The level of sTNFR reflects the true biological activity of TNF-α. We investigated whether sTNF-R in cerebrospinal fluid (CSF) and serum increases during the acute stage in patients with acute encephalitis by measuring p60 sTNF-R using a sandwich enzyme immunoassay. The levels of sTNF-R were significantly higher in the CSF and serum of children with acute encephalitis than in those of control subjects. The patients with acute encephalitis who died or had severe neurological sequelae had higher CSF sTNF-R levels than those who survived. There were no significant differences in the serum sTNF-R, serum C-reactive protein and CSF protein levels, and CSF cell counts between the two groups. The sTNF-R levels of 4.0 ng/ml or higher identified patients with acute encephalitis who had neurological sequelae with a sensitivity of 100% (8/8), a specificity of 100% (8/8), and a predictive value of 100% (8/8). The 95% confidence interval for these three values is 63–100%. Our findings suggest that the CSF level of sTNF-R during the acute stage of encephalitis is important for predicting neurological sequelae.

Intracranial Metastasis of Wilms’ Tumor Involving the Tectal Plate without Pulmonary Involvement

Intracranial metastasis without pulmonary involvement of Wilms’ tumor is very rare, and most previously reported metastatic sites have been in the cerebral parenchyma. We experienced a rare case of metastasis of Wilms’ tumor in the tectal plate without pulmonary involvement. A 3-month-old boy was admitted to our hospital due to hydrocephalus. After insertion of a ventriculoperitoneal shunt, there were no neurological deficits. Five months after the operation, a mass 5 cm in diameter extending from the tectal plate into the third ventricle was found. A mass 10 cm in diameter within the retroperitoneal space, which occupied the right kidney, was also found. Both tumors were resected and diagnosed histologically as Wilms’ tumor. Despite every effort including chemotherapy and radiotherapy, the patient died at 14 months old. The majority of children with hydrocephalus showing thickening of the tectal plate would most likely have tectal glioma; however, this unusual case report reminds us that metastasis of Wilms’ tumor can occur in the tectal plate causing hydrocephalus.

Three-dimensional reconstruction of the power flow Doppler imaging of intracranial vascular structures in the neonate.

Three‐dimensional (3D) ultrasonography reconstructing from power flow Doppler imaging (PF) is able to image the 3D structures of the vascular systems. We tried to display the 3D images of intracranial vascular structures in 5 neonates with a portable data processor. Data acquisition was performed using PF through the anterior fontanel. We succeeded in reconstructing vivid 3D images of the anterior cerebral arteries (ACA), basilar artery (BA), internal carotid arteries (ICA), middle cerebral arteries (MCA), lenticulostriate arteries (LSA), internal cerebral vein (ICV), the vein of Galen (GV) and straight sinus (SS) in all subjects. The MCA could be displayed in only a proximal portion. The images of the LSAs were fainter than the other vessels. These problems are based on the character of PF; the flow signal, sampling from the small sized vessels and the perpendicular vessels to ultrasonic beam, is weak. The images of these vessels are fainter than other vessels. These limitations of PF performance directly influence the quality of the 3D images. The benefits and limitations of 3D ultrasonography system are discussed.

Safety from thromboembolism using intravenous immunoglobulin therapy in Kawasaki disease: Study of whole‐blood viscosity

Abstract Background : High‐dose intravenous infusions of immunoglobulin (IVIG) are well established as a standard therapy for Kawasaki disease (KD) for reducing the risk of coronary artery aneurysms. IVIG therapy might increase the blood viscosity both in vitro and in vivo, which has been reported as a risk factor for cardiovascular or cerebrovascular thromboembolism in adults.

Abnormalities of brain perfusion in echovirus type 30 meningitis

From May to August 1998 an epidemic of aseptic meningitis (AM) due to echovirus type 30 (E30) occurred in Yamaguchi prefecture, Japan. We performed single-photon emission-computed tomography (SPECT) to evaluate cerebral perfusion during the acute stage in 27 patients with AM due to E30. Moreover, we measured the cerebrospinal fluid (CSF) concentrations of soluble tumor necrosis factor receptor (sTNF-R) and interleukin-1 beta (IL-1beta) in all 27 patients, and the serum concentration of soluble E-selectin (sE-selectin) in 19 of the 27 patients, which is responsible for vasculitis, by means of a sandwich enzyme-linked immunosorbent assay. In 20 of the 27 (74.1%) children, SPECT imaging revealed localized cerebral hypoperfusion without abnormal focal neurological findings or symptoms. Follow-up SPECT after about 1 month revealed no abnormalities. The CSF concentrations of sTNF-R and IL-1beta, and the serum concentration of sE-selectin in the group with abnormal findings on SPECT were significantly higher than those in the group without abnormal findings on SPECT and the control subjects. Our results indicate that transient reduced regional blood flow is a frequent finding in children with AM due to E30 infection and that this abnormal finding may be induced by cerebral vasculitis.