Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and 2-acetylaminophenanthrene

Formation and removal of hepatic DNA adducts was studied inmale Sprague-Dawley rats following single injections of twohepatocarcinogens, N-hydroxy-2-acetylaminofluorene (N-OH-AAF)and N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and a nonhepatocarcinogen,N-hydroxy-2-acetylaminophenanthrene (N-OH-AAP) at 0.5 h, 1.5h, 4 h, 24 h, 9 d and 29 d. Using a previously described ³²P-postlabelingassay, maximal DNA binding of these compounds was observed atapproximately 1.5 h, 0.5 h and 24 h, respectively. In additionto the formation of three already known C8- and N2-acetylatedand C8-deacetyiated guanine derivatives and several minor unknownadducts with N-OH-AAF, a set of four new major adducts was alsodetected. These comprised 50% of the total adducts during thefirst 4 h. The three known adducts amounted to 58, 16 and 6%of the 1.5-h value after 24 h, 9 d and 29 d, respectively, whilethe bulk (>84%) of the new major adducts were removed fromthe DNA within 24 h and found only in traces after 9 d. N-OH-AABPformed several unknown minor adducts, in addition to the onemajor C8-deacetylated and two minor C8- and N2-acetylated guaninederivatives; only the C8-deacetylated and N2-acetylated adductswere detected after 29 d. In the case of N-OH-AAP, two majorand several minor adducts were detected, most of which werefound to be deacetylated, and as much as 60% of the adductsmeasured at 24 h were still present after 9 d treatment. Thesedata indicte that certain DNA adducts are repaired rapidly,while others persist for long periods.     

Rationale and design of the Kidney Precision Medicine Project

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Utility of diffusion-weighted MR imaging in the diagnosis of placenta accreta spectrum abnormality

Purpose

The aim of this study was to evaluate the utility of added DWI sequences as an adjunct to traditional MR imaging in the evaluation of abnormal placentation in patients with suspicion for placenta accreta spectrum abnormality or morbidly adherent placenta (MAP).

Materials and methods

The study was approved by local ethics committee. The subjects included pregnant women with prenatal MRI performed between July 2013 to July 2015. All imaging was performed on a Philips 1.5T MR scanner using pelvic phased-array coil. Only T2-weighted and diffusion-weighted imaging (DWI) series were compiled for review. Two randomized imaging sets were created: set 1 included T2-weighted series only (T2W); set 2 included T2W with DWI series together (T2W + DWI). Three radiologists, blinded to history and pathology, reviewed the imaging, with 2 weeks of time between the two image sets. Sensitivity, specificity, and overall accuracy for MAP were calculated and compared between T2W only and T2W + DWI reads. Associations between imaging findings and invasion on pathology were tested using the Chi-squared test. Confidence scores, inter-reader agreement, and systematic differences were documented.

Results

A total of 17 pregnant women were included in the study. 8 cases were pathologically diagnosed with MAP. There were no significant differences in the diagnostic accuracy between T2W and T2W + DWI in the diagnosis of MAP in terms of overall accuracy (62.7% for T2W vs. 68.6% for T2W + DWI, p = 0.68), sensitivity (70.8% for T2W vs. 95.8% for T2W + DWI, p = 0.12), and specificity (55.6% for T2W vs. 44.4% for T2W + DWI, p = 0.49). There was no significant difference in the diagnostic confidence between the review of T2W images alone and the T2W + DWI review (mean 7.3 ± 1.8 for T2W vs. 7.5 ± 1.8 for T2W + DWI, p = 0.37).

Conclusion

With the current imaging technique, addition of DWI sequence to the traditional T2W images cannot be shown to significantly increase the accuracy or reader confidence for diagnosis of placenta accreta spectrum abnormality. However, DWI does improve identification of abnormalities in the placental–myometrial interface.

     

Expression of CD105 and CD34 receptors controls BMP‐induced in vitro mineralization of mouse adipose‐derived stem cells but does not predict their in vivo bone‐forming potential

Adipose‐derived stem cells (ADSCs) can be excellent alternative to bone marrow derived stem cells for enhancing fracture repair since ADSCs can be isolated comparatively in large numbers from discarded lipoaspirates. However, osteogenic potential of ADSCs in vivo is very controversial. We hypothesized that adipose‐derived stem cells (ADSCs) that respond maximally to bone morphogenetic proteins (BMPs) in vitro would possess maximum bone‐forming potential. Four purified populations of mouse ADSCs: CD105⁺CD34⁺, CD105^?CD34^?, CD105⁺CD34^? and CD105^?CD34⁺ were obtained using fluorescence‐activated cell sorting (FACS) and their BMP‐responsiveness was determined in vitro. CD105⁺CD34^? population showed the strongest response to BMPs in terms of robust increase in mineralization. Expression of CD105 correlated with high BMP‐responsive phenotype and larger cell size while expression of CD34 correlated with low BMP‐responsive phenotype and smaller cell size. CD105⁺CD34^? population displayed higher gene expression of Alk1 or Alk6 receptors in comparison with other populations. However, CD105⁺CD34^? ADSCs failed to induce ectopic bone formation in vivo after they were transplanted into syngeneic mice, indicating that in vitro BMP‐responsiveness is not a good indicator to predict in vivo bone forming potential of ADSCs. Therefore greater precautions should be executed during selection of competent ADSCs for bone repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:625–632, 2015.

     

Interferon gamma and T cells inhibit osteogenesis induced by allogeneic mesenchymal stromal cells

The mesenchymal stromal cells (MSCs) are reported to be immunoprivileged and osteogenic. We hypothesized that the use of allogeneic MSCs for bone repair was possible if they displayed an ability to induce similar osteogenesis in syngeneic as well as in allogeneic hosts. To test this hypothesis we used a cloned bone marrow derived cell, termed D1, isolated from Balb/c mice. The D1 cells were subcutaneously injected in syngeneic Balb/c, allogeneic immunocompetent B6, allogeneic T‐cell deficient NCr nude, and allogeneic B6 Pfp?/? Rag2?/? mice that lack matured T and B cells as well as NK‐cell cytolytic functions. D1 cells formed ectopic bones only in syngeneic or allogeneic immunocompromised hosts but not in allogeneic B6 hosts. The lack of T cells alone in allogeneic NCr mice was sufficient to promote osteogenesis in allogeneic environment. We observed a significantly higher number of T cells, B cells, macrophages and significantly higher expression of interferon gamma (IFN‐γ) in B6 allogeneic implants as compared to the syngeneic implants. These factors correlated with severe inhibition of expression of alkaline phosphatase, osteocalcin, and runx2 genes in the implants from B6 mice. Our data suggest that strategies to inhibit T cells and IFN‐γ functions will be useful for bone repair mediated by allogeneic MSCs. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 227–234, 2013     

MRI of female urethra and periurethral pathologies

Introduction and hypothesis

Accurate diagnosis of a wide spectrum of urethral/periurethral pathologies in women remains challenging due to its anatomical location and nonspecific clinical presentations. Magnetic resonance imaging (MRI) has emerged as the modality of choice for diagnosing female urethral and periurethral pathologies due to its multiplanar scanning capability, superior soft tissue differentiation, noninvasive nature, and overall excellent contrast resolution.

Methods

In this narrative review, we describe the use of MRI to visualize the female urethra and periurethral pathologies.

Results

MRI can confidently characterize lesions into cystic or solid, provide a more succinct differential diagnosis, and in some cases provide a specific and accurate diagnosis, enabling surgeons to prepare a roadmap before operative procedure. Moreover, functional MRI can be useful to assess dynamic disorders such as urethral hypermobility.

Conclusions

We provide a comprehensive review of normal MR anatomy of the female urethra, as well as the MR features of practically important urethral and periurethral lesions.

     

The development of antisera to prostaglandins B2 and F2alpha and their analysis using solid-phase and double antibody radioimmunoassay methods.

1 A method for the production of highly substituted prostaglandin-bovine serum albumin conjugates has been developed. 2 Antisera to prostaglandins B2 and F2alpha were raised in rabbits immunized with prostaglandin-bovine serum albumin conjugates. 3 The antisera were assessed for specificity and sensitivity by the double antibody radioimmunoassay method and after they were covalently linked to powdered cellulose to form a 'solid-phase' system. 4 Solid phase radioimmunoassays were developed using conventional shaking and in the presence of sucrose which obviates the need for continuous mixing of the incubates.