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Biomedical subjects

Shuichi Ito

Publications and source records attributed to Shuichi Ito.

At least 19 recordsLinked to original sources

Amelioration of steroids and cyclosporine-resistant nephrotic syndrome by pravastatin.

We report the case of a girl with steroids and cyclosporine (CsA) resistant focal segmental glomerulosclerosis (FSGS) whose proteinuria and hypoproteinaemia were dramatically resolved by pravastatin. She had been in a nephrotic condition for 6 years. Prednisolone, pulse methylprednisolone therapy, low-density lipoprotein (LDL) apheresis, CsA, cyclophosphamide and mizoribine (MZR) had proved to be ineffective. She was started on pravastatin for her hyperlipidaemia 6 and a half years from onset, in addition to the baseline therapy, which included CsA; remission of the nephrotic syndrome was unexpectedly attained after 10 months of treatment. The baseline therapy has not been changed since the inclusion of pravastatin. This case suggests that, in patients with hyperlipidaemia, the response to CsA could be restored by lowering cholesterol levels with statins. The decrease of cholesterol levels might have improved the pharmacokinetics of CsA in this patient. Furthermore, the anti-inflammatory and immuno-modulatory effects, recently attributed to statins, may also have been involved in the improvement experienced by our patient.

Adolescent↗

Intravenous gamma globulin for thrombotic microangiopathy of unknown etiology.

We encountered the case of a 4-year-old boy with thrombotic microangiopathy (TMA) of unknown etiology. Verotoxin-induced hemolytic uremic syndrome (HUS), Streptococcus-pneumoniae-related HUS, factor H deficiency, drug-induced thrombotic thrombocytopenic purpura (TTP), and ADAMTS13 (von Willebrand factor-cleaving protease; a disintegrin-like and metalloprotease with thrombospondin type 1 repeats)-related TTP were excluded. His condition was refractory to anticoagulants and plasma exchange, and his clinical course was catastrophic, with central nervous system symptoms and progressive renal failure. However, factual treatment of intravenous gamma globulin (IVIG) ended the hemolysis and resulted in a rise in platelet count. He fully recovered except for end-stage renal failure, but he underwent a successful renal transplant after peritoneal dialysis. He has not suffered a relapse of TMA or an allograft rejection for 4 years. IVIG might be an option for some patients with TMA of unknown etiology refractory to conventional treatment.

Biopsy↗

CpG oligodeoxynucleotides protect newborn mice from a lethal challenge with the neurotropic Tacaribe arenavirus.

The innate immune system is key to limiting the early spread of most pathogens and directing the development of Ag-specific immunity. Recently, a number of synthetic molecules that activate the innate immune system by stimulating TLRs have been identified. Among them, synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) were shown to activate TLR9-bearing B cells, macrophages, and dendritic cells to induce a strong proinflammatory milieu and a type 1-biased immune response that protects mice from a variety of parasitic, bacterial, and viral infections. Although the protective effect of CpG ODN in adult mice was well established, its effectiveness in neonates, which have lower numbers of dendritic, B, and T cells and tend to favor Th2 responses, was unclear. This study uses the New World arenavirus Tacaribe, a neurotropic pathogen that is lethal in newborn mice, to explore the effectiveness of TLR-mediated innate immune responses. Neonatal BALB/c mice treated with CpG ODN at the time of infection had reduced viral load (p < 0.01) and increased survival (52%, p < 0.001 i.p.; 36%, p < 0.05 intranasally). Protection was achieved in mice treated no later than 3 days postchallenge and appears to be mediated by an increase in Ag-specific Abs (IgG and IgM) and to require inducible NO synthase expression and NO production. To our knowledge, this is the first study assessing the mechanisms by which CpG ODN can protect mice from a neurotropic viral infection.

Animals↗

Evaluation of the effect of water-uptake on the impedance of dental resins.

UNLABELLED: Electrical impedance spectroscopy (EIS) offers a quantitative method of measuring the stability of resin films in aqueous solution over time. PURPOSE: The purpose of this study was to measure the EIS of five experimental dental adhesive films (ca. 17 microm thick) of increasing hydrophilicity (ranked by their Hoy's solubility parameters), and how much these values change over 3 weeks in aqueous buffer. METHODS: The resin films were placed in a U-shaped chamber and a pair of Ag-AgCl electrodes was used for EIS. The EIS results were confirmed by immersing the films in 50% AgNO3 for 24 h to trace the distribution of any water absorption into the resins by TEM observations. RESULTS: The resistance (Rr) of the resins 1-4 films increased most during the first day, and varied from 1x10(11) ohm for resin 1, to 40Omega for resin 5 at day 1. The day 1 Rr values of resins 1-4 were inversely proportional to their Hoy's solubility parameter for hydrogen bonding forces. Electrical impedance values of resins 1-3 and 5 varied widely but were relatively constant over time, while those of resin 4 decreased more than 99% from day 1 to 21 (p<0.05). Capacitance (Cr) of films of resins 1-4 all increased over the first day and then were relatively unchanged over the 20 days (except for resin 4 that continued to increase) and were between 0.01 and 1 nF. Silver uptake by TEM revealed the development of water-filled branching structures that formed in resins 4 and 5 over time.

Adhesives↗

Norovirus-associated encephalopathy.

Norovirus is a common cause of gastroenteritis. We describe the case of a 23-month-old girl with encephalopathy possibly associated with norovirus infection. The viral genome was detected in stool, serum and cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction. This is the first report of encephalopathy potentially caused by norovirus as indicated by the presence of the virus genome in CSF.

Caliciviridae Infections↗

Effect of melatonin injected into the third ventricle on growth hormone secretion in Holstein steers.

The effects of melatonin (MEL) injection into the third ventricle (3V) on growth hormone (GH) secretion were investigated in conscious Holstein steers. A stainless steel cannula was stereotaxically implanted in the 3V based on the ventriculogram. In Exp. 1, three doses of MEL (100, 300 or 600 microg) were injected into the 3V through the cannula and the GH concentration after the injection was determined. In Exp. 2, intracerebroventricular (icv) and intravenous (iv) injections of MEL (100 microg) and GH-releasing hormone (GHRH; 0.25 microg/kg body weight), respectively, were performed simultaneously to examine the effect of MEL on GHRH-induced GH release. The icv injection of MEL significantly stimulated GH release at 100 microg. The increase in GH concentrations by 100 microg of MEL was persistent. Intravenous injection of GHRH dramatically increased GH release. The injection of MEL did not alter GHRH-induced GH release. These results suggest that MEL stimulates GH secretion possibly through the hypothalamus in cattle.

Animals↗

Water content and apparent stiffness of non-caries versus caries-affected human dentin.

Caries-affected dentin contains less mineral and more water than surrounding normal dentin. Such dentin should be less stiff and should shrink more than normal dentin when dried. The purpose of this study was to test the relationships between the stiffness, shrinkage, and water content of caries-affected versus normal dentin. Extracted human carious third molars were stained with caries-detector dye and the occlusal surfaces ground down until only caries-affected dentin remained, surrounded by normal dentin. Dentin disks were prepared from these crowns placed in a aluminum well positioned under a modified thermal mechanical analyzer. Changes in specimen height and stiffness were measured following drying or static loading in both caries-affected and surrounding normal dentin. Core samples of these two types of dentin were used to gravimetrically measure water content. Two-way ANOVA and regression analysis was used to test the relationship between shrinkage versus water content, stiffness versus water content, and stiffness versus shrinkage. Caries-affected dentin was found to be less stiff and contained more water than normal dentin (p < 0.05). Regression analysis revealed highly significant inverse relationships between stiffness and water content, and stiffness and shrinkage (p < 0.0005).

Dental Caries↗

CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection.

Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) can increased the resistance of adult mice to many infectious pathogens, including Listeria. This work examines the capacity of CpG ODN to stimulate a protective immune response in newborns. Results indicate that dendritic cells, macrophages, and B cells from 3-day-old mice respond to CpG stimulation by secreting IFN-gamma, IL-12, and/or TNF-alpha. Spleen cells from CpG-treated neonates produce large amounts of cytokine and NO when exposed to bacteria in vitro. Newborns treated with CpG ODN are protected from lethal Listeria challenge and generate Ag-specific CD4 and CD8 T cells that afford long-term protection against subsequent infection. These results demonstrate that cellular elements of the neonatal immune system respond to stimulation by CpG ODN, thereby reducing host susceptibility to infectious pathogens.

Adjuvants, Immunologic↗

Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice.

OBJECTIVE: Synthetic oligodeoxynucleotides (ODN) expressing TTAGGG motifs suppress the production of proinflammatory cytokines and have been proven effective at blocking the development of certain organ-specific autoimmune diseases. We undertook this study to determine whether suppressive ODN alter the development of systemic autoimmunity, by evaluating their effect on the progression of lupus-like disease in NZB x NZW (NZB/NZW) mice. METHODS: We repeatedly treated mice with suppressive ODN before or after the onset of proteinuria. We monitored the effect of treatment on the onset, severity, and immunologic correlates of disease. RESULTS: Treatment with suppressive ODN significantly prolonged lifespan while delaying the onset and progression of glomerulonephritis in NZB/NZW mice. Clinical improvement was accompanied by a significant reduction in anti-double-stranded DNA autoantibody production and by significantly reduced secretion of interferon-gamma and interleukin-12 in vivo. CONCLUSION: Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus.

Animals↗

CpG-activated Thy1.2+ dendritic cells protect against lethal Listeria monocytogenes infection.

Synthetic oligodeoxynucleotides containing CpG motifs (CpG ODN) activate the innate immune system by interacting with Toll-like receptor 9. The resultant immune response increases host resistance to infection by a variety of pathogenic microorganisms, including Listeria monocytogenes. There is a considerable interest in harnessing the immunoprotective properties of CpG ODN, yet little is known of the cell phenotype(s) responsible for mediating this protection. This work demonstrates that treatment of mice with CpG ODN increases the number of Thy1.2+, CD11c+ dendritic cells (Thy1.2+ DC) in the spleen, which are both necessary and sufficient for transferring resistance to infection from CpG-treated donors to naive recipients. These CpG-activated Thy1.2+ DC are distinct from conventional (CD11c(hi), Thy1.2-) or plasmacytoid DC (mPDCA+), and secrete IFN-gamma that contributes to protection. These findings suggest that a novel Thy1.2+ DC subset plays a critical role in mediating the immunoprotective activity of CpG DNA.

Adoptive Transfer↗

Permeability of adhesive resin films.

The purpose of this study was to quantify the permeability of adhesive resin films to water by measuring convective flow across thin films. Cured resin films were prepared with the use of five commercially available adhesive resins and an experimental resin. Two types of resin films were prepared from solvated comonomer blends within each product; resin films made before or after evaporation of solvent (10 s of drying with air-syringe). The permeability of the resin films was measured 30 min or 24 h after polymerization by placing the films in a split-chamber device. Fluid filtration rate through the resin films was measured with the use of 20 cm of water pressure. Osmotically induced water movement was measured by applying hypertonic aqueous solutions of CaCl2 or HEMA to the resin films. The results showed that evaporation of solvent before polymerization reduced the permeability of adhesive resin films, compared to permeabilities obtained without solvent evaporation. The cured adhesive resin films were all permeable to water, but to varying degrees.

Adhesives↗

Effects of resin hydrophilicity on water sorption and changes in modulus of elasticity.

UNLABELLED: As acidic monomers of self-etching adhesives are incorporated into dental adhesives at high concentrations, the adhesive becomes more hydrophilic. Water sorption by polymers causes plasticization and lowers mechanical properties. The purpose of this study was to compare the water sorption and modulus of elasticity (E) of five experimental neat resins (EX) of increasing hydrophilicity, as ranked by their Hoy's solubility parameters and five commercial resins. METHODS: After measuring the initial modulus of all resin disks by biaxial flexure, half the specimens were stored in hexadecane and the rest were stored in water. Repeated measurements of stiffness were made for 3 days. Water sorption and solubility measurements were made in a parallel experiment. RESULTS: None of the specimens stored in oil showed any significant decrease in modulus. All resins stored in water exhibited a time-dependent decrease in modulus that was proportional to their degree of water sorption. Water sorption of EX was proportional to Hoy's solubility parameter for polar forces (delta(p)) with increasing polarity resulting in higher sorption. The least hydrophilic resin absorbed 0.55 wt% water and showed a 15% decrease in modulus after 3 days. The most hydrophilic experimental resin absorbed 12.8 wt% water and showed a 73% modulus decrease during the same period. The commercial resins absorbed between 5% and 12% water that was associated with a 19-42% reduction in modulus over 3 days.

Absorption↗

Different patterns of cytokines, ECP and immunoglobulin profiles at two adverse drug reactions in a patient.

OBJECTIVES: Drug-induced hypersensitivity syndrome (HS) is a rare but life-threatening disease. We experienced carbamazepine-induced HS in a 14-year-old boy, who had cefaclor-induced cutaneous eruptions 15 months later. To clarify the mechanisms of HS and the differences between two diseases we studied this case in detail. METHODS: We investigated the associated viral agents by polymerase chain reaction and the specific antibodies. We also studied the mechanism of diseases by measuring chemical mediators including cytokines, ECP and immunoglobulins. RESULTS: The patient was diagnosed as having carbamazepine-induced HS associated with reactivation of human herpesvirus 6 based on the clinical course and laboratory data including drug-induced lymphocyte stimulation tests. Similarly, the diagnosis of cefaclor-induced eruption without any viral reactivation was made. Serum levels of IFN-gamma, IL-6, TNF-alpha, IL-5 and ECP were increased significantly at HS but mildly at cefaclor-induced eruptions. Furthermore, we detected transient hypogammaglobulinemia only at HS. CONCLUSIONS: This is the first report of anticonvulsant-induced HS followed by antibiotic-induced eruptions in a patient. In addition, we demonstrated difference in serum levels of inflammatory cytokines, immunoglobulins, activated eosinophils and viral reactivation between these diseases. This case would contribute to the understanding of the pathophysiology of adverse drug reactions including HS.

Adolescent↗

Contribution of nitric oxide to CpG-mediated protection against Listeria monocytogenes.

Immunostimulatory CpG oligodeoxynucleotides (ODN) improve host resistance to listeriae. CpG ODN trigger immune cells to produce gamma interferon and "prime" host cells to secrete nitric oxide in response to bacterial exposure. CpG treatment does not protect inducible nitric oxide synthase 2 knockout mice, indicating that NO is critical to CpG-mediated protection against listeriae.

Adjuvants, Immunologic↗

CpG oligodeoxynucleotides increase the susceptibility of normal mice to infection by Candida albicans.

Synthetic oligodeoxynucleotides containing CpG motifs trigger an innate immune response that typically increases host resistance to infection. Yet CpG treatment reduces the resistance of normal mice to Candida albicans infection. This effect is mediated by CpG-induced interleukin-12, indicating that CpG-dependent cytokine production may have adverse consequences for the host.

Adjuvants, Immunologic↗

Conversion of one-step to two-step self-etch adhesives for improved efficacy and extended application.

PURPOSE: One-step self-etch adhesives have restricted use due to their acid-base incompatibility with autocured composites and their behavior as permeable membranes after polymerization. This study examined the feasibility of their conversion to two-step self-etch adhesives via the adjunctive use of a non-solvented, relatively hydrophobic resin coating. METHODS: iBond, Xeno III and Adper Prompt were used either in multiple coats, or in a single coat followed by the use of a layer of Scotchbond Multi-Purpose Plus bond resin for coupling to light- and auto-cured composites. Four types of experiments were performed. Bonded specimens were examined with TEM after immersion in an ammoniacal silver nitrate tracer. Fluid flow measurements of iBond were conducted using the two application protocols to compare the permeability of the bonded dentin with the original smear layer. Permeability of vital dentin bonded with both application protocols were compared for the transudation of dentin fluid across the bonded dentin. Microtensile bond strengths of dentin bonded with the two protocols were examined for their compatibility with an auto-cured composite. RESULTS: The results of the four experiments were complementary. iBond and Xeno III exhibited "apparent incompatibility" to auto-cured composites that resulted from their inherent permeability. This was confirmed by the presence of dentin fluid transudate on the adhesive surfaces when they were bonded to vital dentin. Conversely, Adper Prompt exhibited "true incompatibility" to auto-cured composites that was caused by adverse acid-base interaction, masking the inherent permeability of this adhesive. "True" and "apparent" incompatibility issues were eliminated upon their conversion to two-step self-etch adhesives.

Bisphenol A-Glycidyl Methacrylate↗