Antimetastatic effect of CpG DNA mediated by type I IFN.

The mechanisms involved in the antimetastatic effect of CpG-containing DNA were investigated in a mouse model of experimental metastasis. Tumor cell colony formation in lungs or livers of mice after i.v. inoculation with syngeneic fibrosarcoma or thymoma cells was determined. The i.v. injection of plasmid DNA or synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs before tumor cell application strongly inhibited metastasis. Because synthetic CpG-ODN was not directly tumor cytotoxic, the target cells for this CpG-ODN effect were determined. The cytotoxic activity on standard natural killer (NK) targets as well as on fibrosarcoma cells of splenic NK cells and NKT cell-containing liver mononuclear cells derived from CpG-ODN-treated mice was strongly enhanced. Participation of NK/NKT cells in the CpG-induced antimetastatic effect was demonstrated by reduction of the antimetastatic effect in mice depleted of NK/NKT cells and beta2-microglobulin-deficient mice. Neutralization of interleukin 12, interleukin 18, or IFN-gamma did not interfere with the CpG-induced antimetastatic effect. However, in sera of CpG-ODN-treated mice, high levels of IFN-alpha were detected, and in IFN-alpha/beta receptor-deficient mice, the CpG-ODN-induced antimetastatic effect was strongly reduced. These data indicate that CpG-ODNs activate NK/NKT cells for antimetastatic activity indirectly via IFN-alpha/beta receptor activation. The exploitation of the stimulatory activity of CpG-ODN for the innate immune system might be a useful strategy for antimetastatic therapy.     

Interferon beta 1, an intermediate in the tumor necrosis factor alpha-induced increased MHC class I expression and an autocrine regulator of the constitutive MHC class I expression

In conclusion, our observations indicate that the constitutive MHC class I expression is regulated by autocrine production of IFN-beta 1. TNF-alpha acts as an enhancer of the autocrine production of IFN-beta 1, and consequently as an enhancer of the MHC class I expression and viral protection.     

Histological assessment of pre‐transplant kidney biopsies is reproducible and representative

Snoeijs M G J, Boonstra L A, Buurman W A, Goldschmeding R, van Suylen R J, van Heurn L W E & Peutz‐Kootstra C J
(2010) Histopathology 56, 198–202 Histological assessment of pre‐transplant kidney biopsies is reproducible and representative Aims: Histological examination of pre‐transplant renal biopsy specimens can be used to select grafts from older donors after cardiac death (DCD) with a satisfactory transplant outcome. The aim was to determine whether such biopsy specimens can be reproducibly scored between pathologists and are representative of the whole kidney. Methods and results: In renal biopsy specimens from DCD aged ≥60 years (n = 44), globally sclerosed glomeruli, vascular narrowing, tubular atrophy and interstitial fibrosis were scored by three independent pathologists according to the Pirani scoring system. Interobserver agreement on the sum of scores improved considerably with the introduction of a combined tubulo‐interstitial scoring system (intraclass correlation coefficient increased from 0.38 to 0.64). In small needle biopsy specimens (n = 144) obtained at autopsy, estimates of the proportion of globally sclerosed glomeruli were more precise with increasing sample size. Reasonably precise estimates may be obtained from specimens with at least seven glomeruli. Conclusions: It is feasible to implement pre‐transplant renal biopsy specimen analysis as a selection criterion in clinical practice in order to accept kidneys from marginal donors for transplantation.     

Ankle: surface coil MR imaging at 1.5 T

High-field surface coil magnetic resonance (MR) images were obtained of 12 ankles: two from healthy volunteers, seven from patients, and three from fresh cadavers. The cadaver ankles were sectioned in the coronal, sagittal, and axial planes for direct comparison with the MR images. Plain film confirmation of pathologic conditions was obtained in all patients, and five underwent arthroscopy or surgery, or both. MR imaging provided excellent delineation of ligaments and cartilaginous structures in all cases.     

Management of cerebral ischemia due to Takayasu''''s arteritis

Ａｏｒｔｏａｒｔｅｒｉｔｉｓ ,ａｌｓｏｃａｌｌｅｄＴａｋａｙａｓｕ’ｓａｒｔｅｒｉｔｉｓ ,ｉｓａｃｈｒｏｎｉｃｉｄｉｏｐａｔｈｉｃｉｎｆｌａｍｍａｔｏｒｙｄｉｓｅａｓｅｔｈａｔａｆｆｅｃｔｓｌａｒｇｅａｎｄｍｅｄｉｕｍｓｉｚｅａｒｔｅｒｉｅｓ Ｃｌｉｎｉｃａｌｆｅａｔｕｒｅｓｒｅｆｌｅｃｔｌｉｍｂｏｒｏｒｇａｎｉｓｃｈｅｍｉａｒｅｓｕｌｔｉｎｇｆｒｏｍｓｔｅｎｏｓｉｓｔｏｏｂｌｉｔｅｒａｔｉｏｎｏｆｉｎｖｏｌｖｅｄａｒｔｅｒｉｅｓ Ｔｈｉｓｄｉｓｅａｓｅ ,ｄｅｓｃｒｉｂｅｄｂｙＴａｋａｙａｓｕｉｎ…     

Local treatment of renal allografts, a promising way to reduce the dosage of immunosuppressive drugs. Comparison of various ways of administering prednisolone

A method is described for continuous administration of immunosuppressive drugs directly into rat renal allografts. The drug is given via a catheter, introduced into the suprarenal or testicular artery of the transplanted kidney. The cannula is connected to an implantable osmotic minipump that delivers an immunosuppressive drug with continuous flow for 13 days. It is demonstrated that the technique as such has no detrimental or enhancing effects on renal allograft survival. Depending upon the pharmacokinetic properties of the drug administered, this technique allows a more or less selective treatment of renal allograft rejection. The method was used to test the effect of intrarenal administration of prednisolone on renal allograft survival. Intrarenal administration of this drug appeared to be superior to any other way of administration tested. A low dose of 4 mg/kg body weight per day given by continuous intrarenal infusion results in significant prolongation of graft survival, whereas continuous systemic administration of this dose is not effective. To induce prolongation of graft survival by i.p. administration the prednisolone dose had at least to be doubled. The results prove that during graft rejection local events within the graft are vulnerable to prednisolone. It is concluded that local treatment of allograft rejection is possible and that this approach represents a potentially important way to manipulate the immune response.     

Utilization of target-specific, hypersensitive strains of Saccharomyces cerevisiae to determine the mode of action of antifungal compounds

Target-specific hypersusceptible strains of Saccharomyces cerevisiae were used to screen antifungal compounds. Two novel Erg7p inhibitors were identified, providing proof of principle of the approach taken. However, observed hypersensitivities to antifungals acting via other targets imply that use of this tool to identify the mode of action requires significant deconvolution.     

Adverse reactions in blood donors with a history of seizures or epilepsy

BACKGROUND: Individuals with epilepsy or seizure disorders are restricted from donating blood because of concern that they are prone to adverse donor reactions such as syncope and convulsions. A study evaluating whether that concern is warranted is reported. STUDY DESIGN AND METHODS: During a 2-year period beginning in 1987, blood donors in Maryland with a history of seizures were actively recruited by the American Red Cross. Adverse donor reactions were classified as "slight", indicating dizziness and nausea without loss of consciousness; "moderate," denoting syncope; and "severe," indicating convulsive syncope. RESULTS: There were 329,143 satisfactory blood donations; 613 individuals reporting a history of seizures donated blood a total of 723 times. Among donors with seizures, 186 (35.7%) were taking antiepileptic medication, and 61 (8.4%) had had one or more seizures in the preceding year. Individuals with seizures had a low incidence of adverse reactions (3.34%). Although this incidence was slightly higher than that in the entire population (2.24%), the difference was not significant. In particular, the risk of syncope with or without convulsive activity was low for people with seizures (0.21%) and not significantly greater than that in other donors (0.28%). CONCLUSION: Individuals with seizures or epilepsy are not at greater risk for adverse reactions after blood donation, and major restrictions on their participation as blood donors are not warranted.