Objective: The aim of this study was to compare the diagnostic performances of digital tomosynthesis (DTS) and conventional radiography in detecting osteonecrosis of the femoral head (ONFH) using computed tomography (CT), as the reference standard and evaluate the diagnostic reproducibility of DTS. Materials and Methods: Forty-five patients (24 male and 21 female; age range, 25–77 years) with clinically suspected ONFH underwent anteroposterior radiography, DTS, and CT. Two musculoskeletal radiologists independently evaluated the presence and type of ONFH. The diagnostic performance of radiography and DTS in detecting the presence of ONFH and determining the types of ONFH were evaluated. The interobserver and intraobserver reliabilities of each imaging modality were analyzed using Cohen’s kappa. Results: DTS had higher sensitivity (89.4%–100% vs. 74.5%–76.6%) and specificity (97.3%–100% vs. 78.4%–83.8%) for ONFH detection than radiography. DTS showed higher performance than radiography in identifying the subtypes of ONFH with statistical significance in one reader (type 1, 100% vs. 30.8%, p = 0.004; type II, 97.1% vs. 73.5%, p = 0.008). The interobserver agreement was excellent for DTS and moderate for radiography (kappa of 0.86 vs. 0.57, respectively). The intraobserver agreement for DTS was higher than that of radiography (kappa of 0.96 vs. 0.69, respectively). Conclusion DTS showed higher diagnostic performance and reproducibility than radiography in detecting ONFH. DTS may be used as a first-line diagnostic modality instead of radiography for patients suspected of having ONFH.

Enzyme/prodrug approach is one of the actively developing areas for cancer therapy. In an effort to develop more effective enzyme/prodrug systems, cell-permeable cytosine deaminase was produced by fusing yeast cytosine deaminase (yCD) in frame with RKKRRQRRR domain of HIV-1 Tat which is an efficient delivery peptide of the foreign proteins into cells. The purified Tat-yCD fusion protein expressed in Escherichia coli was readily transduced into mammalian cells in a time- and dose-dependent manner. A significant level of the transduced Tat-yCD protein was recovered in the cell and was stable for 24 h as indicated by both results of the enzymatic assay of 5-fluorocytosine (5-FC) conversion to 5-fluorouracil (5-FU) and Western blot analysis. The cells transduced with Tat-yCD become highly sensitive to the cytotoxicity of 5-FC, while cells treated with yCD are unaffected by 5-FC. In addition, a strong bystander effect was observed with conditioned media from cells transduced with Tat-yCD added to non-transduced cells. Tat-yCD fusion protein demonstrated here for its ability to transduce into cells and convert nontoxic prodrug 5-FC to the toxic antimetabolite 5-FU, may be a useful approach for cancer therapy.
Animals ; Antimetabolites/*metabolism/pharmacology ; Bystander Effect ; Cytosine Deaminase/genetics/*metabolism ; Flucytosine/*metabolism/pharmacology ; Gene Products, tat/chemistry/genetics/*metabolism ; Genetic Vectors/genetics/metabolism ; HIV-1/metabolism ; Hela Cells/drug effects/physiology ; Humans ; Prodrugs/metabolism/therapeutic use ; Recombinant Fusion Proteins/genetics/*metabolism ; Research Support, Non-U.S. Gov't ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; *Transduction, Genetic

One of characteristic features of AIDS-related encephalitis and dementia is the infiltration of monocytes into the CNS. HIV-1 Tat was demonstrated to facilitate monocyte entry into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of adhesion molecules, generation of reactive oxygen species (ROS) and NF-kappaB activation in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein and mRNA levels of ICAM-1 and VCAM-1, as measured by Western blot analysis and RT-PCR, indicating that Tat increases these protein levels at an mRNA level. In addition, Tat induced the activation of NF-kappaB in astrocytes. Treatment of CRT-MG with NF-kappaB inhibitors led to decrease in Tat-induced protein and mRNA expression of ICAM-1 and VCAM-1. Furthermore, HIV-1 Tat protein increased ROS generation. Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kappaB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG. These data indicate that HIV-1 Tat can modulate monocyte adhesiveness by increasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS- and NF-kappaB-dependent mechanisms in astrocytes.
Vascular Cell Adhesion Molecule-1/genetics/*metabolism ; Up-Regulation/*drug effects ; Transcription, Genetic/genetics ; Reactive Oxygen Species/*metabolism ; NF-kappa B/*metabolism ; Monocytes/cytology/*drug effects/metabolism ; Intercellular Adhesion Molecule-1/genetics/*metabolism ; Humans ; *HIV-1 ; Gene Products, tat/*pharmacology ; Cell Line ; Cell Adhesion/drug effects ; Astrocytes/cytology/metabolism

OBJECTIVE: This study aimed to examine the association between normal-but-low folate levels and cognitive function in the elderly population using a prospective cohort study. METHODS: We analyzed 3,910 participants whose serum folate levels were within the normal reference range (1.5–16.9 ng/mL) at baseline evaluation in the population-based prospective cohort study named the “Korean Longitudinal Study on Cognitive Aging and Dementia.” The association between baseline folate quartile categories and baseline cognitive disorders [mild cognitive impairment (MCI) or dementia] was examined using binary logistic regression analysis adjusting for confounding variables. The risks of incident MCI and dementia associated with the decline of serum folate level during a 4-year follow-up period were examined using multinomial logistic regression analysis. RESULTS: The lowest quartile group of serum folate (≥1.5, ≤5.9 ng/mL) showed a higher risk of cognitive disorders than did the highest quartile group at baseline evaluation (odds ratio 1.314, p=0.012). Over the 4 years of follow-up, the risk of incident dementia was 2.364 times higher among subjects whose serum folate levels declined from the 2nd–4th quartile group to the 1st quartile than among those for whom it did not (p=0.031). CONCLUSION: Normal-but-low serum folate levels were associated with the risk of cognitive disorders in the elderly population, and a decline to normal-but-low serum folate levels was associated with incident dementia. Maintaining serum folate concentration above 5.9 ng/mL may be beneficial for cognitive status.
Aged ; Cognition ; Cognition Disorders ; Cognitive Aging ; Cohort Studies ; Confounding Factors (Epidemiology) ; Dementia ; Folic Acid ; Follow-Up Studies ; Humans ; Logistic Models ; Longitudinal Studies ; Prospective Studies ; Reference Values