Distinct difference in tumor-infiltrating immune cells between Wilms' tumor gene 1 peptide vaccine and anti-programmed cell death-1 antibody therapies.

Background: Wilms' tumor gene 1 (WT1) peptide vaccine and anti-programmed cell death-1 (anti-PD-1) antibody are expected as immunotherapies to improve the clinical outcome of glioblastoma. The aims of this study were to clarify how each immunotherapy affects tumor-infiltrating immune cells (TIIs) and to determine whether the combination of these two therapies could synergistically work.

Methods: Mice were transplanted with WT1 and programmed cell death-ligand 1 doubly expressing glioblastoma cells into brain followed by treatment with WT1 peptide vaccine, anti-PD-1 antibody, or the combination of the two, and survival of each therapy was compared.

Identification of mouse helper epitopes for WT1-specific CD4 T cells.

Helper T lymphocytes (HTLs) play a central role in cancer immunity because they can not only help the induction and proliferation of cytotoxic T lymphocytes (CTLs) but also their differentiation into cytotoxic CD4 T cells and directly kill the target cells.This study describes the identification of three novel mouse Th epitope peptides, WT1, WT1 and WT1 derived from WT1 protein, which is the most potent tumor-associated antigen. Compared to immunization with WT1 CTL peptide alone, immunization with the addition of these WT1-specific Th peptides strongly induced WT1-specific CTLs, continued to maintain them, and efficiently rejected the challenge of WT1-expressing tumor cells.

Reactions of (Arylimido)vanadium(V)-Trialkyl Complexes with Phenols: Effects of Arylimido Ligands and Phenols for Formation of the Vanadium Phenoxides.

Reactions of a series of (arylimido)vanadium(V) trialkyl complexes, V(NAr')(CHSiMe) (Ar' = CH, 2-MeCH, 2,6-MeCH, 2,6-ClCH), with various phenols (ArOH, Ar = 2,6-FCH, 2,6-ClCH, 2,6-MeCH, 2,6- PrCH, 2- BuCH, 2,6- BuCH; 1.0 equiv) affording V(NAr')(CHSiMe)(OAr) were conducted in CD at 25 °C, and the effects of both arylimido ligands and phenols on the substitution rate were explored. Sterically hindered arylimido ligands showed lower reactivity, and the reaction proceeded in the order: Ar' = 2,6-MeCH < 2,6-ClCH < 2-MeCH < CH.

Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides.

In immunotherapy by cancer antigen-derived peptide vaccine, vaccination of cytotoxic T lymphocyte (CTL) peptide alone is common, while it remains unclear whether the addition of helper peptide vaccine to the CTL peptide vaccine is of great advantage for the enhancement of tumor immunity. In the present study, combination vaccine of Wilms' tumor gene 1(WT1) protein-derived CTL and helper peptides induced the strong infiltration of WT1-specific CD8 T cells into mouse tumor at frequencies of 8.8%, resulting in the formation of multiple microscopic necrotic lesions in the tumor, whereas the frequencies of WT1-specific CD8 T cell infiltration into the tumor in the vaccination of the CTL peptide alone were only 0.

Facile in situ generation of highly active (arylimido)vanadium(v)-alkylidene catalysts for the ring-opening metathesis polymerization (ROMP) of cyclic olefins by immediate phenoxy ligand exchange.

Highly active catalysts for the ring-opening metathesis polymerization (ROMP) of cyclic olefins (norbornene, cyclopentene, cycloheptene) can be generated in situ by premixing V(CHSiMe)(NCF)(O-2,6-PrCH)(PMe) (1) with 1.0 equiv. of CFOH or CClOH via the immediate phenoxy exchange; the activity was affected by the kind of phenol added [activity (TOF) in the ROMPs of norbornene: 46 200 min (upon addition of CFOH) vs.

Early predictors of status epilepticus-associated mortality and morbidity in children.

Background: Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk.

Objectives: To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children.

Methods: We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination.

Incidence of pediatric IgA nephropathy.

Immunoglobulin A (IgA) nephropathy progresses without apparent signs. The only available means of knowing the precise incidence of this disease in children is to analyze data from the school urinary screening system. Students between 6 and 15 years old with IgA nephropathy detected by school urinary screening from 1983 to 1999 in Yonago City, Japan, were examined.

Highly-sensitive micellar electrokinetic chromatographic analysis of dioxin-related compounds using on-line concentration.

An application study of an on-line concentration technique of neutral analytes for micellar electrokinetic chromatography (MEKC) was carried out in environmental analysis to enhance the UV detection sensitivity. Several dioxins and related compounds, such as dibenzofuran, dibenzo-p-dioxin, 2,3- and 2,7-dichlorodibenzo-p-dioxins, and 2,3,7-trichlorodibenzo-p-dioxin, were used as test solutes. For a highly sensitive separation and detection, cyclodextrin-modified MEKC (CD-MEKC) under acidic conditions was employed as a separation mode and stacking using reverse migrating micelles and a water plug (SRW) as an on-line concentration technique.

[Transitions of each inhibitor in a patient with lupus anticoagulant and anti-prothrombin antibody].

In a 2-year-old girl showing purpura on her legs after administration of antibiotics, marked prolongation of activated partial thromboplastin time(APTT) and prothrombin time was noted. Circulating anticoagulants were demonstrated by the failure to correct APTT on neutralization test. A lupus anticoagulant(LA), one of the circulating anticoagulants, was detected by rabbit brain phospholipid neutralization procedure and platelet neutralization procedure.

Epstein-Barr virus (EBV)-carrying and -expressing T-cell lines established from severe chronic active EBV infection.

Four novel Epstein-Barr virus (EBV)-carrying T-cell lines, designated SIS, AIK-T8, AIK-T4, and SKN, were established from peripheral blood lymphocytes (PBL) of patients with severe chronic active EBV infection, in the presence of interleukin-2 and 4-deoxyphorbol ester. AIK-T8 and -T4 were derived from a single patient. Cell marker and genotype analyses showed that SIS, AIK-T8, and AIK-T4 had mature T-cell phenotypes with clonally rearranged T-cell receptor (TCR) genes, whereas SKN had an immature T-cell phenotype without TCR gene rearrangement.

Two independent outbreaks of measles in partially vaccinated junior high schools in Tottori, Japan.

We analyzed retrospectively a relative risk of measles attacks in vaccinated vs. unvaccinated students using two independent outbreaks in Japan. The first involved 33/328 (10%) students where 64% students and 30% measles cases had been vaccinated.

[The clinical study of cefpodoxime proxetil dry syrup preparation in the pediatric field].

The clinical efficacy was examined for the newly developed oral cephem antibiotic, cefpodoxime proxetil (CPDX-PR) dry syrup, in the treatment of various acute infections in the field of pediatrics. CPDX-PR dry syrup was administered at 10 mg/kg/day in 3-divided doses to 535 children at 21 institutions, including Tottori University Hospital and its related hospitals. The efficacy rate of this drug was determined to be 80.

Immunodeficiency with increased immunoglobulin M associated with growth hormone insufficiency.

Growth hormone deficiency associated with hypogammaglobulinemia has been reported only in a few publications. Our patient was a male with recurrent episodes of infections. Serum immunoglobulin (Ig) G was extremely low although IgM concentration was much greater than the normal limit.

Normal levels of IgG subclass in childhood determined by a sensitive ELISA.

Normal values of all IgG subclasses were determined using a sensitive ELISA in children aged from newborn to 14 years. The upper and lower limits of normal values of all IgG subclasses were obtained in all the age groups using 29 umbilical cord blood samples from full-term newborns and 308 venous blood samples from normal infants and children. The trends in the levels of IgG1, IgG2 and IgG3 with age were almost similar to previous reports.

Suppressive effect of superoxide dismutase on adriamycin nephropathy.

A single intravenous injection of adriamycin (ADR) results in marked proteinuria and glomerular morphological changes that are similar to minimal-change disease in humans. We examined the effect of superoxide dismutase (SOD) on ADR-induced proteinuria. ADR in a dose of 7.

[Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 3). Combined effect on metastatic tumors].

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamous cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma.

[Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 2). Combined effect on the MM102 syngeneic tumor].

C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone.

A new synthetic pathway to adenine-2-d, 9-alkyladenine-2-d, adenosine-2-d, and 2'-deoxyadenosine-2-d.

Unambiguous assignments of the purine ring protons in the NMR spectra of adenine (Ia) and its 9-substituted derivatives (Ib-f) have been made by comparison with those of the isotopically labeled adenines VIIIa-f. 9-Alkyl-2-deuterioadenines (VIIIb-d), adenosine-2-d (VIIIe), and 2'-deoxyadenosine-2-d (VIIIf) were synthesized from the 9-substituted adenines Ib-f through cyclization of the monocyclic intermediates VIb-f with formic acid-d2 or 1-(formyl-d)-2(1H)-pyridone. Hydrolysis of VIIIe with 0.