Nano-particle motion in a monolithic silica column using the single-particle tracking method.

Porous materials are used in a variety of industrial applications owing to their large surface areas, large pore volumes, hierarchical porosities, and low densities. The motion of particles inside the pores of porous materials has attracted considerable attention. We investigated nano-particle motion in a porous material using the single-particle tracking method. Particle motion such as absorption and desorption at the wall was observed. The displacement probability distribution deviated from the Gaussian distribution at the tail, indicating non-Gaussian motion of the particles. Moreover, an analysis of the relative angle between three consecutive particle positions revealed that the probability of the particle moving backward was approximately twice that of the particle moving forward. These results indicate that particle motion inside porous materials is highly complex and that a single-particle study is essential for fabricating a structure that is suitable for applications.

Pressure-Sensitive Nano-Sheet for Optical Pressure Measurement.

Pressure-Sensitive Paint (PSP) is a powerful measurement technique to obtain pressure distribution on a model of interest by measuring the emission intensity of the PSP coating with a camera. Since a PSP coating is prepared by applying a solution containing an organic solvent, generally, by sprayer, the properties such as the pressure- and the temperature-sensitivity depends on the skill of the person applying it. This fabrication process is one of the barriers to use of the PSP technique because of the legal restrictions on the use of organic solvents. Thus, a sticker-like PSP coating is useful because it does not require the use of organic solvent and the applying skill. In this study, we have fabricated freestanding Pressure-Sensitive Nano-Sheet (PSNS) by a sacrificial layer process using a spin-coating method. We employed Pt(II) meso-tetra(pentafluorophenyl)porphine (PtTFPP) as a pressure-sensitive dye and poly(1-trimethylsilyl-propyne) (PTMSP) and poly(L-lactic acid) (PLLA) as a polymer binder; thus, the PSNS samples based on PTMSP and PLLA were prepared. The pressure- and the temperature-sensitivity, the lifetime of the luminescence, and the quantum yield of the fabricated PSNS have been investigated. The pressure-sensitivity of PTMSP-based PSNS is higher than that of PLLA-based PSNS. Conversely, the quantum yield of PLLA-based PSNS is higher than that of PTMSP-based PSNS.

Prenatal nicotine exposure affects cardiovascular function and growth of the developing fetus.

AIM: Effects of nicotine on fetal hemodynamics are not well known, especially in the first trimester fetus. We investigated the acute and chronic effects of nicotine on hemodynamics in pregnant mice and their fetuses using ultrasound. Postnatal health status including growth and hemodynamics was also examined. METHODS: To investigate the acute effects of nicotine on fetal hemodynamics, we injected nicotine 0.2 mg/kg subcutaneously into pregnant mice on gestational days (GD) 9.5, 11.5 and 13.5 and compared with saline-injected group. To determine the chronic effects of nicotine on fetal hemodynamics, we administered nicotine in drinking water (0.1 mg/mL) to pregnant mice from GD 6.5 until they gave birth and compared hemodynamics with water-administered mice. RESULTS: Regarding the acute effects of nicotine, we found no intergroup difference in maternal hemodynamics; however, fetal blood flow through the dorsal aorta, carotid artery and umbilical artery tended to decrease, particularly on GD 11.5. Regarding the chronic effects of nicotine, we observed no intergroup difference in maternal body weight changes and hemodynamics; however, blood flow to all fetal organs tended to be lower in the nicotine water group than in the water group with significant difference on GD 13.5. The offspring of the nicotine water group had significantly low birth weights and continued to have low body weight until 9 weeks of age. In addition, these offspring developed postnatal cardiac hypertrophy. CONCLUSION: Nicotine adversely affects fetal hemodynamics acutely and chronically in early pregnancy, potentially leading to fetal tissue hypoxia, intrauterine growth restriction and adverse postnatal health effects.

Maintaining Concentration of Ribavirin in Cerebrospinal Fluid by a New Dosage Method; 3 Cases of Subacute Sclerosing Panencephalitis Treated Using a Subcutaneous Continuous Infusion Pump.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a slow virus infectious disease resulting from persistent infection with mutant measles virus. At present, there is no effective treatment for SSPE. Interferon-α and inosine pranobex have both been used for the treatment of SSPE, and partial success has been reported for the antiviral drug, ribavirin (RBV). The standardization of dosage method is necessary to carry out treatment with RBV more safely and effectively. In this study, RBV concentrations in cerebrospinal fluid (CSF) were monitored during the intraventricular administration using a subcutaneous continuous infusion pump. METHODS: Three patients with new-onset SSPE were treated with RBV using a subcutaneous continuous infusion pump. On days 3-10 after the start of RBV infusion, CSFs were obtained by lumbar tap, and the concentration of RBV in the CSF was measured using high-performance liquid chromatography. RESULTS: RBV concentration increased in a dose-dependent manner in all 3 patients, and the target concentration could be generally maintained without any severe side effects. We observed that the clinical symptoms were temporarily relieved in each case. In the 2 cases for whom treatment is continuing, the patients remain in stage III, while the patient who discontinued the therapy progressed to stage IV. CONCLUSION: The target RBV concentration in the CSF could be maintained continuously by intraventricular administration using a subcutaneous continuous infusion pump. The accumulation of further cases is necessary to confirm the safety and efficacy of this medical treatment.

A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo.

Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-type MV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-to-cell spread. It contains two critical heptad repeat regions that form a six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein. We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model.

[A patient with an early diagnosis of PCDH19-related epilepsy].

An abnormality in PCDH19 causes intractable early-onset epilepsy limited to females, and its significance in pediatric epilepsy is currently increasing. We report the case of a girl with an early diagnosis of PCDH19-related epilepsy. Focal seizures, consisting of eye deviation and asymmetrical tonic posturing, first appeared in clusters at the age of 5 months. Although each seizure was brief (less than a few minutes), seizures occurred in clusters. Cluster was observed at ages of 7, 10, 11, 14, and 19 months, respectively, and all were intractable to multiple treatments. Each cluster continued for 3 days to 2 weeks. However, no seizures occurred outsides the clusters. The pattern of seizure occurrences was characteristic of PCDH19-related epilepsy, which we first suspected when the patient was 11 months old. Genetic analysis of PCDH19 revealed two novel missense substitutions: c.1294G≥C (p.D417H) and c.1786G≥T (p.D596Y). Her psychomotor development was normal at the last follow-up at age of 1 year and 9 months. Currently, the pathogenesis and best treatments of PCDH19-related epilepsy remain unclear. However, to provide correct diagnosis and genetic counseling, and to avoid overtreatments, the possibility of this disease should be considered early in girls with intractable seizure clusters which starting during infancy to early childhood.

Characteristics of viruses derived from nude mice with persistent measles virus infection.

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 10(2) PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 10(4) PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.

Mumps virus-associated acute encephalopathy: case report and review of the literature.

We describe a fatal case of mumps virus-associated acute encephalopathy. In terms of the clinical course and cytokine as well as chemokine profiles, the pathogenesis in our case was different from that of mumps meningoencephalitis but was similar to that of influenza virus-associated acute encephalopathy.

Role of vascular endothelial growth factor and angiopoietin 1 in renal injury in hemolytic uremic syndrome.

BACKGROUND/AIMS: The recovery process from renal injury in hemolytic uremic syndrome (HUS) remains obscure. In order to clarify the role of vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) in the renal recovery from HUS, we produced a model of mild HUS and examined the renal recovery process. METHODS: We investigated three groups of mice. Group 1 consisted of mice that received an injection of Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS); group 2 consisted of mice that received an injection of low dose of Stx2 and LPS, and group 3 consisted of control mice. RESULTS: Serum Cr levels in group 1 were greater than those in group 2, and all mice in group 1 died, whereas all mice in group 2 remained alive. Endothelial injury at 24 h in group 1 was higher than in group 2. Electron-microscopic findings demonstrated that the endothelial cells formed immature capillary-like lumina from 7 to 28 days with increases in the expression of CD31-positive cells. Glomerular VEGF expression decreased at 72 h in group 1, but gradually increased in group 2. Glomerular Ang-1 expression peaked from 72 h to 28 days. Ang-1 expression was frequently found in the endothelial cell region of vesicle walls simultaneous with increased CD31-positive staining. CONCLUSION: Our findings suggest that VEGF and Ang-1 play important roles in the recovery process, particularly in the regeneration of endothelial injury.

Survey of subacute sclerosing panencephalitis in Japan.

Investigators conducted a retrospective epidemiological study of subacute sclerosing panencephalitis, a fatal disease caused by measles infection, over the past few years in Japan. Data on 118 cases obtained from a questionnaire sent to attending physicians were analyzed. The annual incidence of subacute sclerosing panencephalitis was approximately 0.03 cases per million from 2001 to 2005. Children infected with measles at a young age (<12 months) showed a high incidence of subacute sclerosing panencephalitis, and those infected before 6 months of age showed earlier onset. Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.

The role of serum myeloid-related protein 8/14 complex in Henoch-Schönlein purpura nephritis.

Myeloid-related protein (MRP) 8/14 complex is a marker of monocyte and neutrophil activation. We evaluated whether serum MRP8/14 complex is associated with clinical manifestations and pathological findings of Henoch-Schönlein purpura nephritis (HSPN). Patients were divided into two groups based on serum MRP8/14 complex levels at renal biopsy. Group 1 consisted of 18 HSPN patients with less than median (670 ng/ml) MRP8/14 complex levels, and Group 2 of 12 HSPN patients with greater than median levels. Clinical manifestations, laboratory findings and serum E-selectin levels, as a marker of vascular endothelial cell dysfunction, as well as histological and immunohistochemical findings were investigated for both groups. We also measured MRP8/14 complex levels in disease control and healthy control children. Urinary protein excretions, serum MRP8/14 complex levels, and serum E-selectin levels were all higher in Group 2 than in Group 1 patients. Serum MRP8/14 complex levels were higher in HSPN patients than in controls. Serum MRP8/14 complex levels were strongly associated with serum E-selectin levels. Pathological findings revealed that the proportions of patients with ISKDC grades III, IV and V in Group 2 were higher than in Group 1. Our findings suggest that serum MRP8/14 complex levels might be associated with the severity of renal injury and endothelial cell dysfunction in HSPN patients.

Development of common variable immunodeficiency in IgA- and IgG2-deficient patients with systemic lupus erythematosus.

BACKGROUND: There have been few reports on children who developed common variable immunodeficiency (CVID) in association with immunoglobulin A (IgA) and IgG2 deficiencies and systemic lupus erythematosus (SLE). CASE-DIAGNOSIS/TREATMENT: Our patient experienced nephrotic syndrome and acute respiratory distress syndrome (ARDS) caused by influenza A/H1N1 virus infection at 5 years of age. A diagnosis of IgA and IgG2 deficiency and SLE was made on the basis of severe proteinuria, hematuria, hypocomplementemia, high anti-DNA antibody and antinuclear antibody (ANA) titers, and malar rash. However, these clinical signs and symptoms and laboratory features disappeared after the administration of methylprednisolone pulse therapy and prednisolone. For the 5 years following the initial treatment for SLE, the patient experienced a number of infections and had a low serum total IgG level; she was eventually diagnosed with CVID. The administration of intravenous immunoglobulin (IVIG) was required to prevent subsequent infections, and no relapse of SLE was observed. CONCLUSION: We report the development of CVID in an IgA- and IgG2-deficient patient with SLE on the basis of multiple episodes of infection. To prevent the development of CVID in IgA- and IgG2-deficient patients with SLE, it is important to prevent immune dysregulation by the avoidance of infections through the use of IVIG therapy.

Uteroglobulin-related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital.

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.

A 10-year-old girl with IgA nephropathy who 5 years later developed the characteristic features of Henoch-Schönlein purpura nephritis.

We report a patient who developed Henoch-Schönlein purpura (HSP) 5 years after she presented with immunoglobulin A nephropathy (IgAN). A 10-year-old Japanese female was identified with proteinuria and hematuria by a school urinary screening. The first renal biopsy showed mesangial proliferative glomerulonephritis with immunofluorescent findings consistent with IgAN. She was treated with prednisolone, warfarin, and dilazep dihydrochloride, and the proteinuria and hematuria disappeared 4 months after the onset of treatment. Five years later she developed abdominal pain, gross hematuria and a classic purpuric rash of HSP after acute pharyngitis. The second renal biopsy showed diffuse mesangial proliferation with cellular crescent formation, and the patient was treated with methylprednisolone pulse therapy, prednisolone and mizoribine, resulting in a gradual decrease in urinary protein excretion. Our patient is unusual in that she developed Henoch-Schönlein purpura nephritis 5 years after clinical and biopsy evidence of IgAN, which suggests that IgAN and HSP are different clinical manifestations of the same disease, probably sharing a common pathogenesis.

Serum KL-6 levels as a biomarker of lung injury in respiratory syncytial virus bronchiolitis.

To evaluate whether KL-6 concentration is a useful biomarker of the severity of respiratory syncytial virus (RSV) bronchiolitis, we determined KL-6 concentrations in patients with RSV bronchiolitis with or without chronic heart disease (CHD). We enrolled 52 patients who had been diagnosed with RSV bronchiolitis and required admission to the hospital at the Department of Pediatrics of Fukushima Medical University School of Medicine from 2004 to 2005. These patients were divided into two groups: Group 1 consisted of patients without any underlying disease, and Group 2 consisted of patients with CHD. These patients were assigned to three categories. Stage A consisted of patients without oxygen dosage, stage B of patients who required oxygen dosage, and stage C of patients required artificial respiration. We evaluated baseline characteristics, clinical features, and serum KL-6 concentration in Group 1, Group 2, and a control group (healthy infants without infection). Mean serum KL-6 concentrations in patients with RSV bronchiolitis were higher than those in the control group (471.8 +/- 236.9 and 127.1 +/- 69.1 U/ml, respectively). Mean serum KL-6 concentration was higher in Group 2 than in Group 1 (692.8 +/- 313.1 and 390.4 +/- 132.7 U/ml, respectively). Mean serum KL-6 concentrations were higher in stage C than in stages A and B, and mean serum KL-6 concentrations were higher in stage B than in stage A. These findings suggest that serum KL-6 is associated with the severity of RSV bronchiolitis and that it may be a useful biomarker for the severity of RSV bronchiolitis.

RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules.

Human RSV causes an annual epidemic of respiratory tract illness in infants and in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses include inhibition of type I IFN mRNA transcription and blocking signal transduction of JAK/STAT family members. The suppressor of cytokines signaling (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and block the activation of the JAK/STAT signaling pathway. To evaluate the potential of SOCS molecules to subvert the innate immune response to RSV infection, eight SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells. Suppression of SOCS1, SOCS3 and CIS by short interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore, inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing STAT1/2 phosphorylation. These results suggest that RSV infection escapes the innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in epithelial cells.

Tonsillectomy with methylprednisolone pulse therapy as rescue treatment for steroid-resistant IgA nephropathy in children.

Primary immunoglobulin A (IgA) nephropathy is characterized by microhematuria and proteinuria and by the deposition of IgA in the glomerular mesangium. Steroid was a main drug for treatment of IgA nephropathy. However, some of children with IgA nephropathy are resistance to steroid treatment, but the therapy for steroid-resistant IgA nephropathy was not established. There have been reports on the efficacy of tonsillectomy as an initial treatment for IgA nephropathy in adults and children. We examined whether tonsillectomy with methylprednisolone pulse therapy (tonsillectomy pulse therapy) was effective as rescue treatment for steroid-resistant pediatric IgA nephropathy. We studied 11 patients (age at onset and duration of follow-up, 11.7 +/- 2.0 and 6.2 +/- 1.1 years) who had been diagnosed with steroid-resistant IgA nephropathy. Clinical features, laboratory data, and pathological findings were retrospectively compared between before and after tonsillectomy pulse therapy. Urinary protein excretion was significantly decreased at 24.7 +/- 7.3 months after tonsillectomy pulse therapy. On renal pathologic examination of 6 patients who underwent renal biopsy at 17.1 +/- 6.9 months after tonsillectomy pulse therapy, the activity index, an index of inflammation, was lower compared to the index evaluated before the therapy, but the chronic index, an index of renal sclerosis, remained unchanged. At 24.7 +/- 7.3 months after tonsillectomy pulse therapy, seven patients had normal urine and four had minor urinary abnormalities; namely, none had active renal disease or renal insufficiency. Our findings suggest that tonsillectomy pulse therapy may be effective as rescue treatment for steroid-resistant IgA nephropathy in childhood.