Presence of anti-FKBP12 autoantibodies in patients with liver allografts: its association with allograft rejection

BACKGROUND: It was reported that autoantibodies against cyclophilin are present in sera from systemic lupus erythematosus. We hypothesized that autoantibodies against FKBP12, another immunophilin, may be present in the plasma of liver allograft recipients, which may affect the clinical outcome of liver allografts. METHODS: We investigated the relationship between the presence of anti-FKBP12 autoantibodies and rejection episodes in 47 patients treated with FK506 after living-related partial liver transplantation (LRLT). The patients consisted of two groups: 22 with rejection [R(+) group] and 25 without rejection [R(-) group]. The autoantibodies were measured by an indirect ELISA, and the specificity was confirmed by absorption with antigen and immunoblotting. RESULTS: The autoantibodies were detected in 13 of 22 in the R(+) group (IgG: 5; IgM: 6; both: 2) and in 6 of 25 in the R(-) group (IgG: 2; IgM: 3; both: 1) before LRLT (P=0.0193). After LRLT, they were also detected more frequently in the R(+) group (12 of 22; IgG: 1; IgM: 8; both: 3) than in the R(-) group (2 of 25; IgG: 1; IgM: 1) (P=0.001). In the R(+) group, the mortality of the patients who were positive and negative for the autoantibodies was 6 of 12 and 2 of 10, respectively. The autoantibodies were detected in all four patients with chronic or refractory acute rejection. The autoantibodies were not detected in any of the 34 healthy subjects. CONCLUSIONS: These results suggest that the presence of the autoantibodies in patients before transplantation is related to rejection, and the presence after transplantation may be associated with patient outcome.     

Alteration of human platelet protein kinase C with normal aging

Using a two-site enzyme immunoassay, we determined the content of type II protein kinase C (PKC) in human platelets from 24 donors of various ages without any neurological, hematological or malignant disorders. The content of type II PKC in the membranous fraction was positively correlated with aging. The content of PKC in the cytosolic fraction tended to decline with aging, but the correlation was not significant. The total amount of PKC also had no significant correlation with aging. Age-related changes in platelet protein content were not observed. These results suggested that the subcellular distribution of type II PKC in human platelets is altered with normal aging.     

Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury

The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and manageable, although serious AEs, including lung injury (specifically, interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, chronic obstructive pulmonary disease, and poor performance status, indicate that lung inflammatory circumstances may worsen with EGFR-TKI treatment because of impaired epithelial healing of lung injuries. There is limited evidence from preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced ILD in the available literature. Herein, we evaluated the relationship between EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung injury or resistance in cytokine-rich circumstances were reviewed. We discussed the relevance of cytotoxic agents or immunotherapeutic agents in combination with EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed recent developments in diagnostics and therapeutics that facilitate recovery from lung injury or overcoming resistance to anti-EGFR treatment.     

Plasticization of cellulose diacetate by reaction with maleic anhydride,glycerol, and citrate esters during melt processing

To accomplish the stable internal plasticization of cellulose diacetate (CDA), maleic anhydride (MAH) and glycerol (Gly) were used as reactive plasticizers. The plasticization method used was based on a melt‐processing reaction of CDA with MAH and Gly. MAH and Gly (MG)‐plasticized CDA showed stiff and brittle properties; that is, low elongation at break and high modulus. Thus, citrate esters were used as coplasticizers to improve physical properties. The resulted plasticized materials were optically clear, and showed attractive mechanical properties. The grafting of MG oligoesters to the free hydroxyl groups in CDA and their homo‐oligomerization were accelerated by two‐step kneading process, and verified by FTIR and GPC measurements. Differential scanning calorimeter (DSC) analysis revealed decreases of 80–100°C in the glass transition temperature (T_g) of CDA by these plasticizations. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 243–250, 2001     

EVALUATION OF LIQUID-LIQUID PARTITION COEFFICIENTS OF MULTTDENTATE AMINES BY SCALED PARTICLE THEORY

ABSTRACT

For some aliphatic and aromatic bidentate amines, e.g., ethylenedi-amine derivatives, which were used in the synergistic extraction system, the liquid-liquid partition coefficients (P) were measured between benzene and water phases and discussed together with other aliphatic and aromatic multidentate amines by using the scaled particle theory (SPT). The contributions of three kinds of Gibbs energies, i.e, the cavity formation energy (G¯_h), the dispersion energy (G¯_dis) and hydrogen-bonding energy (G¯_h), to the P values were successfully evaluated. The main factor to determine the P value was G¯_h (10–55 kJ/mol) in the aqueous phase, but the contributions of G¯_c (6–15 kJ/mol) and G¯_dis (6–28 kJ/mol) were not negligibly small.     

High-yields heterologous production of the novel Aspergillus fumigatus elastase inhibitor AFUEI in Aspergillus oryzae

AFUEI, an elastase inhibitor produced by Aspergillus fumigatus strongly inhibits the elastolytic activity of A. fumigatus etc. To purify AFUEI, we constructed a strain that overproduces AFUEI by introducing the gene encoding AFUEI (Genbank accession no. AB546725) under control of the amyB promoter into the heterologous host Aspergillus oryzae. A. oryzae TF-4 displayed strong elastase inhibitory activity and produced considerably more AFUEI than that of A. fumigatus. Furthermore, AFUEI could be purified using culture broth and single ultrafiltration (UF) treatment, allowing for the effective production of AFUEI for use in clinical trials.     

Ion exchange resins and ethyleneimine polymer as antioxidants: I. Activity and mechanism

The antioxidant activity of ion exchange resins and ethyleneimine polymer was determined in methyl linoleate free from natural antioxidants and metals. Superior antioxidant activities were recognized in an ion exchange resin with NH groups and in the ethyleneimine polymer. The antioxidant activities in these heterogeneous reaction systems increased in linear proportion to the amount present. These antioxidant activities in the heterogeneous reaction system were mainly owing to their ability to donate hydrogen to the peroxy radicals produced in the autoxidation of methyl linoleate. The antioxidant radicals produced in these cases were very stable and generally couldn’t participate in the increase of the induction periods in the autoxidation of methyl linoleate by terminating the peroxy radicals. These results have never been obtained in the homogeneous reaction system but are characteristic in the heterogeneous one.     

Study and Development of a Screener Test for Fuel Economy Passenger Car Motor Oil

Fuel economy regulations have been issued in many countries to save energy,and it is one of the most essential performance requirements for Passenger Car Motor Oil（PCMO） this decade.The performance is ...     

Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.